Study of Efficacy and Safety of NIS793 (With and Without... | NCT04390763 | Trialant
NCT04390763
Sponsor
Novartis Pharmaceuticals
Status
Terminated
Last Update Posted
Oct 16, 2025Actual
Enrollment
164Actual
Phase
Phase 2
Conditions
Metastatic Pancreatic Ductal Adenocarcinoma
Interventions
NIS793
Spartalizumab
gemcitabine
nab-paclitaxel
Countries
United States
Australia
Austria
Belgium
Czechia
Finland
France
Germany
Italy
Singapore
Spain
Switzerland
Taiwan
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT04390763
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CNIS793B12201
Secondary IDs
ID
Type
Description
Link
2020-000349-14
EudraCT Number
Brief Title
Study of Efficacy and Safety of NIS793 (With and Without Spartalizumab) in Combination With SOC Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC)
Official Title
A Phase II, Open Label, Randomized, Parallel Arm Study of NIS793 (With and Without Spartalizumab) in Combination With SOC Chemotherapy Gemcitabine/Nab-paclitaxel, and Gemcitabine/Nab-paclitaxel Alone in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC)
Acronym
daNIS-1
Organization
NovartisINDUSTRY
Status Module
Record Verification Date
Oct 2025
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
The study was early terminated following the NIS793 treatment halt and urgent safety measure issued in July 2023, as the continued evaluation of Standard of Care alone will not support the original purpose of this phase 2 clinical trial.
Expanded Access Info
No
Start Date
Oct 16, 2020Actual
Primary Completion Date
Apr 26, 2024Actual
Completion Date
May 2, 2024Actual
First Submitted Date
May 14, 2020
First Submission Date that Met QC Criteria
May 14, 2020
First Posted Date
May 18, 2020Actual
Results Waived
Not provided
Results First Submitted Date
Mar 4, 2025
Results First Submitted that Met QC Criteria
May 8, 2025
Results First Posted Date
May 28, 2025Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Oct 8, 2025
Last Update Posted Date
Oct 16, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Novartis PharmaceuticalsINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The purpose of this Phase II study is to assess the efficacy and safety of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in previously untreated mPDAC.
Detailed Description
This is a randomized, parallel arms, open-label, multi-center, Phase II study to evaluate the efficacy and safety of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel in participants with first-line metastatic pancreatic ductal adenocarcinoma (mPDAC).
The study started with a Safety Run-in to assess the safety and tolerability of NIS793 in combination with spartalizumab and standard of care (SOC) gemcitabine/nab-paclitaxel. Doses defined for each study treatment, as part of this quadruplet were administered in the Randomized part in the quadruplet/triplet/doublet-based treatment arms.
The Randomized part opened after the Safety Run-in had completed. Participants were randomized in a 1:1:1 ratio to one of the three treatment arms:
Arm 1: NIS793 with spartalizumab and gemcitabine/nab-paclitaxel
Arm 2: NIS793 with gemcitabine/nab-paclitaxel
Arm 3: gemcitabine/nab-paclitaxel
Conditions Module
Conditions
Metastatic Pancreatic Ductal Adenocarcinoma
Keywords
NIS793
spartalizumab
gemcitabine
nab-paclitaxel
mPDAC
TGFβ
PD-1
Phase II
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
164Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Safety Run-in
Experimental
Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel
Biological: NIS793
Biological: Spartalizumab
Drug: gemcitabine
Drug: nab-paclitaxel
Randomized Arm 1
Experimental
Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel
Biological: NIS793
Biological: Spartalizumab
Drug: gemcitabine
Drug: nab-paclitaxel
Randomized Arm 2
Experimental
Combination of NIS793 + gemcitabine + nab-paclitaxel
Biological: NIS793
Drug: gemcitabine
Drug: nab-paclitaxel
Randomized Arm 3
Active Comparator
gemcitabine + nab-paclitaxel
Drug: gemcitabine
Drug: nab-paclitaxel
Interventions
Name
Type
Description
Arm Group Labels
Other Names
NIS793
Biological
anti-TGFb antibody. NIS793 2100 mg every 2 weeks by intravenous (i.v.) infusion.
Randomized Arm 1
Randomized Arm 2
Safety Run-in
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Safety run-in Part: Number of Participants With Dose-Limiting Toxicities (DLTs)
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 where the relationship to study treatment cannot be ruled out and is not clearly related solely to disease, disease progression, inter-current illness or concomitant medications, which occurs within the DLT evaluation period. The DLT evaluation period is the first 28 days of treatment with NIS793 with spartalizumab in combination with gemcitabine/nab-paclitaxel. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
First cycle of treatment (28 days)
Safety run-in Part: Number of Participants With AEs and SAEs During the On-treatment Period
Number of participants with AEs (any adverse events regardless of seriousness) and serious adverse events (SAEs), including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs.
AE grades to characterize the severity of the AEs were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. For CTCAE v5.0, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE.
The on-treatment period is defined from the day of first administration of any study treatment up to 30 days after the date of the last actual administration of any study drug.
Up to approximately 0.8 years
Safety run-in Part: Number of Participants With Dose Reductions and Dose Interruptions of NIS793, Spartalizumab, Gemcitabine and Nab-paclitaxel
Number of participants with at least one dose reduction and at least one dose interruption of study drugs. Dose adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.
No dose reductions were allowed for NIS793 and spartalizumab beyond the first 28 days period of Safety run-in part.
Up to approximately 0.7 years
Safety run-in Part: Dose Intensity of NIS793 and Spartalizumab
Secondary Outcomes
Measure
Description
Time Frame
Randomized Part: Number of Participants With AEs and SAEs During the On-treatment Period
Number of participants with AEs (any adverse events regardless of seriousness) and serious adverse events (SAEs), including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs.
AE grades to characterize the severity of the AEs were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. For CTCAE v5.0, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE.
The on-treatment period is defined from the day of first administration of any study treatment up to 30 days after the date of the last actual administration of any study drug.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Signed informed consent must be obtained prior to participation in the study.
Male or female ≥ 18 years of age at the time of informed consent.
Participants with histologically or cytologically confirmed treatment-naïve metastatic adenocarcinoma of the pancreas with measurable disease as per RECIST 1.1.
Participants must have a site of disease amenable to biopsy, and be candidate for tumor biopsy according to the treating institution's guidelines. Participants must be willing to undergo a tumor biopsy at screening and during therapy on the study. In the event a new biopsy cannot be safely performed at study entry, an archival sample (collected <6 months prior) may be substituted following documented discussion with Novartis.
ECOG performance status ≤ 1.
Exclusion Criteria:
Previous radiotherapy, surgery (with exception of placement of biliary stent, which is allowed), chemotherapy or any other investigational therapy for the treatment of metastatic pancreatic cancer. Participants having received previous chemotherapy in the adjuvant setting.
Participants amenable to potentially curative resection.
Participants with a diagnosis of pancreatic neuroendocrine tumors (NETs), acinar, or islet cell tumors.
Having out of range laboratory values as pre-defined in the protocol.
Participants with MSI-H pancreatic adenocarcinoma.
Presence of symptomatic CNS metastases, or CNS metastases that require local CNS directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids 2 weeks prior to study entry.
History of severe hypersensitivity reactions to any ingredient of study drug(s) and other mAbs and/or their excipients.
The participant exhibits any of the events outlined in the contra-indications or special warnings and precautions sections of gemcitabine and nab-paclitaxel as per locally approved labels.
Impaired cardiac function or clinically significant cardiac disease.
Known history of testing positive HIV infection.
Active HBV or HCV infection. Participants whose disease is controlled under antiviral therapy should not be excluded.
History of or current interstitial lung disease or pneumonitis grade ≥ 2
High risk of clinically significant gastrointestinal tract bleeding or any other condition associated with or history of significant bleeding.
Pelletier M, Yang J, Joshi M, Grauel A, Abecunas C, Altzerinakou MA, Zhou Z, Zhu X, Clark K, Li L, Bai LY, Milella M, Mercade TM, Tai WMD, Bockorny B, Grell P, Sivakumar S, Wong MK, Chee CE, Aparicio T, Prager G, Bostel G, Schiessl B, Maacke H, Dranoff G, Shaw A, Fabre C, Mataraza J, Malek S, Cremasco V. Biomarker analysis from patients with metastatic PDAC treated with TGFbeta antibody, NIS793, plus abraxane+gemcitabine vs. abraxane+gemcitabine alone in a phase II, open label, randomized study. Clin Cancer Res. 2026 Jun 25. doi: 10.1158/1078-0432.CCR-26-0805. Online ahead of print.
See Also Links
Label
URL
A Plain Language Trial Summary is available on www.novctrd.com
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
The screening period began once patients had signed the study informed consent. Screening evaluations had to be completed within 21 days prior to the first dose of study treatment (≤ 28 days for baseline radiological assessments). After screening, the treatment period started on Cycle 1 Day 1.
Recruitment Details
Participants took part in 31 investigative sites in 14 countries.
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the safety run-in part
FG001
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
Periods
Title
Milestones
Reasons Not Completed
Safety run-in Part
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Apr 18, 2022
Mar 4, 2025
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
Estimated Results First Submitted Date
Not provided
Condition Browse Module
No data available
No data is available for this block.
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Spartalizumab
Biological
anti-PD-1 antibody. spartalizumab 400 mg every 4 weeks by i.v. infusion.
Randomized Arm 1
Safety Run-in
PDR001
gemcitabine
Drug
SOC chemotherapy. Gemcitabine (1000 mg/m^2 on Days 1, 8, and 15) i.v. given as per label.
Randomized Arm 1
Randomized Arm 2
Randomized Arm 3
Safety Run-in
nab-paclitaxel
Drug
SOC chemotherapy. Nab-paclitaxel (125 mg/m^2 on Days 1, 8, and 15) i.v. given as per label.
Randomized Arm 1
Randomized Arm 2
Randomized Arm 3
Safety Run-in
abraxane
Dose intensity of NIS973 and spartalizumab was calculated as cumulative actual dose in milligrams divided by duration of exposure in days and multiplied by 28 days. Dose adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.
Cycle 1 and Cycle 3. The duration of each cycle was 28 days.
Safety run-in Part: Dose Intensity of Gemcitabine and Nab-paclitaxel
Dose intensity of gemcitabine and nab-paclitaxel was calculated as cumulative actual dose in milligrams/m^2 divided by duration of exposure in days and multiplied by 28 days.
Cycle 1 and Cycle 3. The duration of each cycle was 28 days.
Randomized Part: Progression-Free Survival (PFS) Per RECIST v1.1 - Bayesian Model
PFS was based on local review of tumor assessments, using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. If a subject had not had an event, PFS was censored at the date of last adequate tumor assessment.
PFS was estimated using a Bayesian model. For each comparison (arm 1 versus arm 3 and arm 2 versus arm 3), PFS was modeled using a two-piece hazard model, with specifying hazard rates before and after the possible delayed effect for arms 1 and 2 and constant hazard rate for arm 3.
Results in the table as expressed as estimated posterior median hazard rate and one-sided 90% credible interval.
Up to approximately 2 years. Risk changing timepoint=approximately 0.3 years.
Randomized Part: Progression-Free Survival (PFS) Per RECIST v1.1 - Kaplan-Meier Curves and Cox Model
PFS was based on local review of tumor assessments, using RECIST 1.1 criteria. PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. If a subject had not had an event, PFS was censored at the date of last adequate tumor assessment.
PFS was analyzed based on the Kaplan-Meier curves and the Cox model.
Up to approximately 2 years
Up to approximately 1.8 years
Randomized Part: Number of Participants With Dose Reductions and Dose Interruptions of NIS793, Spartalizumab, Gemcitabine and Nab-paclitaxel
Number of participants with at least one dose reduction and at least one dose interruption of study drugs. Dose adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.
No dose reductions were allowed for NIS793 and spartalizumab in the Randomized part.
Up to approximately 1.7 years
Randomized Part: Dose Intensity of NIS973 and Spartalizumab
Dose intensity of NIS973 and spartalizumab was calculated as cumulative actual dose in milligrams divided by duration of exposure in days and multiplied by 28 days. Dose adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.
Cycle 1 and Cycle 3. The duration of each cycle was 28 days
Randomized Part: Dose Intensity of Gemcitabine and Nab-paclitaxel
Dose intensity of gemcitabine and nab-paclitaxel was calculated as cumulative actual dose in milligrams/m^2 divided by duration of exposure in days and multiplied by 28 days.
Cycle 1 and Cycle 3. The duration of each cycle was 28 days
Randomized Part: Overall Response Rate (ORR) Per RECIST v1.1
ORR is the percentage of patients with a confirmed best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.
For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Up to approximately 1.7 years
Randomized Part: Duration of Response (DOR) Per RECIST v1.1
DOR per RECIST v1.1 is defined as the time from the first documented response of CR or PR to the date of the first documented progression or death. DOR only applies to patients with a best overall response of CR or PR by investigator assessment per RECIST v1.1. Participants continuing without progression or death were censored at the date of their last adequate tumor assessment.
DOR was analyzed using the Kaplan-Meier method.
Up to approximately 1.7 years
Randomized Part: Time to Progression (TTP) Per RECIST v1.1
TTP per RECIST v1.1 is defined as the time from the date of randomization to the date of event defined as the first documented progression per RECIST v1.1 or death due to underlying cancer. If a participant had no progression or death, the participant was censored at the date of last adequate tumor assessment.
DOR was analyzed using the Kaplan-Meier method.
Up to approximately 1.7 years
Randomized Part: Overall Survival (OS)
Overall survival is defined as the time from the date of randomization to the date of death due to any cause.
OS was analyzed using the Kaplan-Meier method.
Up to approximately 2 years
Randomized Part: Change From Baseline in PD-L1 Expression
The tumor expression of programmed cell death-ligand 1 (PD-L1) was measured by immunohistochemical methods. Results are expressed as absolute change from baseline in PD-L1 expression.
Baseline (Screening), on-treatment (anytime between Cycle 3 Day 2 and Day 4). The duration of each cycle was 28 days.
Randomized Part: Change From Baseline in CD8 Expression
The tumor expression of CD8 was measured by immunohistochemical methods. Results are expressed as absolute change from baseline in CD8 expression.
Baseline (Screening), on-treatment (anytime between Cycle 3 Day 2 and Day 4). The duration of each cycle was 28 days.
Randomized Part: Number of Participants With Anti-NIS793 Antibodies
The immunogenicity (IG) against NIS793 was assessed in serum using a validated enhanced electrochemiluminescence immunoassay (ECLIA).
Patient anti-drug antibodies (ADA) status was defined as follows:
ADA-negative at baseline: ADA-negative sample at baseline
ADA-positive at baseline: ADA-positive sample at baseline
ADA-negative post-baseline: patient with ADA-negative sample at baseline and at least 1 post baseline sample, all of which are ADA-negative samples
ADA-inconclusive post-baseline = patient who does not qualify as ADA-positive or ADA-negative post-baseline
Treatment-induced ADA-positive = ADA-negative sample at baseline and at least 1 treatment-induced ADA-positive sample
Baseline (before first dose) and post-baseline (assessed throughout the treatment up to approximately 1.7 years)
Randomized Part: Number of Participants With Anti-spartalizumab Antibodies
The immunogenicity (IG) against spartalizumab was assessed in serum using a validated a validated homogenous enzyme-linked immunosorbent assay (ELISA).
Patient anti-drug antibodies (ADA) status was defined as follows:
ADA-negative at baseline: ADA-negative sample at baseline
ADA-inconclusive at baseline: patient who does not qualify as ADA-positive or ADA-negative at baseline
ADA-positive at baseline: ADA-positive sample at baseline
ADA-negative post-baseline: patient with ADA-negative sample at baseline and at least 1 post baseline sample, all of which are ADA-negative samples
ADA-inconclusive post-baseline = patient who does not qualify as ADA-positive or ADA-negative post-baseline
Treatment-induced ADA-positive = ADA-negative sample at baseline and at least 1 treatment-induced ADA-positive sample
Cycle 1 and Cycle 3. The duration of each cycle was 28 days
Randomized Part: Maximum Observed Serum Concentration (Cmax) of NIS793
Pharmacokinetic (PK) parameters were calculated based on NIS793 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed concentration following a dose.
Cycle 1 and Cycle 3: pre-dose, 1, 24, 168 and 336 hours after the end of the infusion on Day 1. The duration of the infusion was 30 minutes. One cycle=28 days
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of NIS793
PK parameters were calculated based on NIS793 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
Cycle 1 and Cycle 3: pre-dose, 1, 24, 168 and 336 hours after the end of the infusion on Day 1. The duration of the infusion was 30 minutes. One cycle=28 days
Randomized Part: Trough Serum Concentration (Ctrough) of NIS793
Ctrough is defined as the concentration reached immediately before the next dose is administered. All drug concentrations below the lower limit of quantification were treated as zero for the calculation of PK parameters.
Cycle 1: pre-dose on Day 1. Cycle 3: pre-dose on Day 1 and Day 15 (combined). One cycle=28 days
Randomized Part: Maximum Observed Serum Concentration (Cmax) of Spartalizumab
PK parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed concentration following a dose.
Cycle 1 and Cycle 3: pre-dose, 1, 24, 168 and 648 hours after the end of the infusion on Day 1. The duration of the infusion was 30 minutes. One cycle=28 days
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Spartalizumab
PK parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
Cycle 1 and Cycle 3: pre-dose, 1, 24, 168 and 648 hours after the end of the infusion on Day 1. The duration of the infusion was 30 minutes. One cycle=28 days
Randomized Part: Trough Serum Concentration (Ctrough) of Spartalizumab
Ctrough is defined as the concentration reached immediately before the next dose is administered. All drug concentrations below the lower limit of quantification were treated as zero for the calculation of PK parameters.
Cycle 2, 3 and 4: pre-dose on Day 1. One cycle=28 days
Randomized Part: Maximum Observed Plasma Concentration (Cmax) of Gemcitabine
PK parameters were calculated based on gemcitabine plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed concentration following a dose.
Cycle 1 and Cycle 4: pre-dose, end of infusion, and 2, 3, 5 and 24 hours after the start of infusion on Day 1. The duration of the infusion was according to the product labelling and local guidance. One cycle=28 days
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Gemcitabine
PK parameters were calculated based on gemcitabine plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
Cycle 1 and Cycle 4: pre-dose, end of infusion, and 2, 3, 5 and 24 hours after the start of infusion on Day 1. The duration of the infusion was according to the product labelling and local guidance. One cycle=28 days
Randomized Part: Trough Serum Concentration (Ctrough) of Gemcitabine
Ctrough is defined as the concentration reached immediately before the next dose is administered. All drug concentrations below the lower limit of quantification were treated as zero for the calculation of PK parameters.
Cycle 4: pre-dose on Day 1. One cycle=28 days
Randomized Part: Maximum Observed Plasma Concentration (Cmax) of Nab-paclitaxel
PK parameters were calculated based on nab-paclitaxel plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed concentration following a dose.
Cycle 1 and Cycle 4: pre-dose, end of infusion, and 2, 3, 5 and 24 hours after the start of infusion on Day 1. The duration of the infusion was according to the product labelling and local guidance. One cycle=28 days
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Nab-paclitaxel
PK parameters were calculated based on nab-paclitaxel plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
Cycle 1 and Cycle 4: pre-dose, end of infusion, and 2, 3, 5 and 24 hours after the start of infusion on Day 1. The duration of the infusion was according to the product labelling and local guidance. One cycle=28 days
Randomized Part: Trough Serum Concentration (Ctrough) of Nab-paclitaxel
Ctrough is defined as the concentration reached immediately before the next dose is administered. All drug concentrations below the lower limit of quantification were treated as zero for the calculation of PK parameters.
Cycle 4: pre-dose on Day 1. One cycle=28 days
Baltimore
Maryland
21231
United States
Massachusetts General Hospital
Boston
Massachusetts
02114
United States
Beth Israel Deaconess Medical Cente
Boston
Massachusetts
02215
United States
Univ of Pittsburgh Cancer Institute
Pittsburgh
Pennsylvania
15232
United States
Novartis Investigative Site
Westmead
New South Wales
2145
Australia
Novartis Investigative Site
Melbourne
Victoria
3000
Australia
Novartis Investigative Site
Salzburg
5020
Austria
Novartis Investigative Site
Vienna
A-1090
Austria
Novartis Investigative Site
Liège
4000
Belgium
Novartis Investigative Site
Brno
Czech Republic
656 53
Czechia
Novartis Investigative Site
Helsinki
FIN-00029
Finland
Novartis Investigative Site
Paris
75475
France
Novartis Investigative Site
Toulouse
31054
France
Novartis Investigative Site
Essen
45147
Germany
Novartis Investigative Site
Heidelberg
69120
Germany
Novartis Investigative Site
Ulm
89081
Germany
Novartis Investigative Site
Milan
MI
20132
Italy
Novartis Investigative Site
Milan
MI
20141
Italy
Novartis Investigative Site
Rozzano
MI
20089
Italy
Novartis Investigative Site
Verona
VR
37134
Italy
Novartis Investigative Site
Singapore
119074
Singapore
Novartis Investigative Site
Singapore
168583
Singapore
Novartis Investigative Site
Barcelona
Catalonia
08035
Spain
Novartis Investigative Site
Barcelona
Catalonia
08036
Spain
Novartis Investigative Site
Madrid
28050
Spain
Novartis Investigative Site
Sankt Gallen
9007
Switzerland
Novartis Investigative Site
Zurich
8091
Switzerland
Novartis Investigative Site
Taichung
40447
Taiwan
Novartis Investigative Site
Taipei
10002
Taiwan
Novartis Investigative Site
Oxford
OX3 7LE
United Kingdom
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
FG002
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
FG003
Arm 3: Gemcitabine/Nab-paclitaxel
Standard of care chemotherapy in the randomized part
FG00011 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Safety Set 1
All patients who received at least one dose of study treatment in the Safety run-in part.
FG00011 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
NOT COMPLETED
FG00011 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Type
Comment
Reasons
Adverse Event
FG0004 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Physician Decision
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Progressive Disease
FG0006 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Randomized Part
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG00150 subjects
FG00251 subjects
FG00352 subjects
Full Analysis Set (FAS)
All patients to whom study treatment was assigned by randomization.
FG0000 subjects
FG00150 subjects
FG00251 subjects
FG003
Safety Set 2
All patients who received at least one dose of study treatment in the Randomized part.
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the safety run-in part
BG001
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
BG002
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
BG003
Arm 3: Gemcitabine/Nab-paclitaxel
Standard of care chemotherapy in the randomized part
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00011
BG00150
BG00251
BG00352
BG004164
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00063.5± 8.77
BG00164.3± 10.91
BG00264.2± 9.90
BG003
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
18 - <65 years
BG0005
BG00120
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0005
BG00121
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
White
BG0009
BG00139
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Safety run-in Part: Number of Participants With Dose-Limiting Toxicities (DLTs)
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 where the relationship to study treatment cannot be ruled out and is not clearly related solely to disease, disease progression, inter-current illness or concomitant medications, which occurs within the DLT evaluation period. The DLT evaluation period is the first 28 days of treatment with NIS793 with spartalizumab in combination with gemcitabine/nab-paclitaxel. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
Dose-Determining Set (DDS) including all participants in the Safety run-in part who met the minimum exposure criterion defined in the protocol and had sufficient safety evaluations after 4 weeks of treatment or experienced a DLT during the first 4 weeks of treatment.
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the safety run-in part
Units
Counts
Participants
OG0006
Title
Denominators
Categories
Any DLT
Title
Measurements
OG0001
Colitis
Title
Measurements
OG0001
Primary
Safety run-in Part: Number of Participants With AEs and SAEs During the On-treatment Period
Number of participants with AEs (any adverse events regardless of seriousness) and serious adverse events (SAEs), including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs.
AE grades to characterize the severity of the AEs were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. For CTCAE v5.0, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE.
The on-treatment period is defined from the day of first administration of any study treatment up to 30 days after the date of the last actual administration of any study drug.
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the safety run-in part
Units
Counts
Participants
OG000
Primary
Safety run-in Part: Number of Participants With Dose Reductions and Dose Interruptions of NIS793, Spartalizumab, Gemcitabine and Nab-paclitaxel
Number of participants with at least one dose reduction and at least one dose interruption of study drugs. Dose adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.
No dose reductions were allowed for NIS793 and spartalizumab beyond the first 28 days period of Safety run-in part.
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the safety run-in part
Units
Counts
Participants
OG000
Primary
Safety run-in Part: Dose Intensity of NIS793 and Spartalizumab
Dose intensity of NIS973 and spartalizumab was calculated as cumulative actual dose in milligrams divided by duration of exposure in days and multiplied by 28 days. Dose adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.
Patients in the Safety set 1 who received NIS793 or spartalizumab at each reported treatment cycle.
Posted
Mean
Standard Deviation
mg per cycle
Cycle 1 and Cycle 3. The duration of each cycle was 28 days.
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the safety run-in part
Units
Counts
Participants
OG000
Primary
Safety run-in Part: Dose Intensity of Gemcitabine and Nab-paclitaxel
Dose intensity of gemcitabine and nab-paclitaxel was calculated as cumulative actual dose in milligrams/m^2 divided by duration of exposure in days and multiplied by 28 days.
Patients in the Safety set 1 who received gemcitabine or nab-paclitaxel at each reported treatment cycle.
Posted
Mean
Standard Deviation
mg per m^2 per cycle
Cycle 1 and Cycle 3. The duration of each cycle was 28 days.
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the safety run-in part
Units
Counts
Participants
OG000
Primary
Randomized Part: Progression-Free Survival (PFS) Per RECIST v1.1 - Bayesian Model
PFS was based on local review of tumor assessments, using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. If a subject had not had an event, PFS was censored at the date of last adequate tumor assessment.
PFS was estimated using a Bayesian model. For each comparison (arm 1 versus arm 3 and arm 2 versus arm 3), PFS was modeled using a two-piece hazard model, with specifying hazard rates before and after the possible delayed effect for arms 1 and 2 and constant hazard rate for arm 3.
Results in the table as expressed as estimated posterior median hazard rate and one-sided 90% credible interval.
Full Analysis Set (FAS)
Posted
Median
90% Confidence Interval
events (progression, death) per year
Up to approximately 2 years. Risk changing timepoint=approximately 0.3 years.
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
Primary
Randomized Part: Progression-Free Survival (PFS) Per RECIST v1.1 - Kaplan-Meier Curves and Cox Model
PFS was based on local review of tumor assessments, using RECIST 1.1 criteria. PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. If a subject had not had an event, PFS was censored at the date of last adequate tumor assessment.
PFS was analyzed based on the Kaplan-Meier curves and the Cox model.
Full Analysis Set (FAS)
Posted
Median
95% Confidence Interval
months
Up to approximately 2 years
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
OG002
Arm 3: Gemcitabine/Nab-paclitaxel
Standard of care chemotherapy in the randomized part
Secondary
Randomized Part: Number of Participants With AEs and SAEs During the On-treatment Period
Number of participants with AEs (any adverse events regardless of seriousness) and serious adverse events (SAEs), including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs.
AE grades to characterize the severity of the AEs were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. For CTCAE v5.0, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE.
The on-treatment period is defined from the day of first administration of any study treatment up to 30 days after the date of the last actual administration of any study drug.
Safety set 2
Posted
Count of Participants
Participants
Up to approximately 1.8 years
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
OG002
Arm 3: Gemcitabine/Nab-paclitaxel
Secondary
Randomized Part: Number of Participants With Dose Reductions and Dose Interruptions of NIS793, Spartalizumab, Gemcitabine and Nab-paclitaxel
Number of participants with at least one dose reduction and at least one dose interruption of study drugs. Dose adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.
No dose reductions were allowed for NIS793 and spartalizumab in the Randomized part.
Safety set 2
Posted
Count of Participants
Participants
Up to approximately 1.7 years
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
OG002
Arm 3: Gemcitabine/Nab-paclitaxel
Standard of care chemotherapy in the randomized part
Secondary
Randomized Part: Dose Intensity of NIS973 and Spartalizumab
Dose intensity of NIS973 and spartalizumab was calculated as cumulative actual dose in milligrams divided by duration of exposure in days and multiplied by 28 days. Dose adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.
Patients in the Safety set 2 who received NIS793 or spartalizumab at each reported treatment cycle.
Posted
Mean
Standard Deviation
mg per cycle
Cycle 1 and Cycle 3. The duration of each cycle was 28 days
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
OG002
Arm 3: Gemcitabine/Nab-paclitaxel
Standard of care chemotherapy in the randomized part
Secondary
Randomized Part: Dose Intensity of Gemcitabine and Nab-paclitaxel
Dose intensity of gemcitabine and nab-paclitaxel was calculated as cumulative actual dose in milligrams/m^2 divided by duration of exposure in days and multiplied by 28 days.
Patients in the Safety set 2 who received gemcitabine or nab-paclitaxel at each reported treatment cycle
Posted
Mean
Standard Deviation
mg per m^2 per cycle
Cycle 1 and Cycle 3. The duration of each cycle was 28 days
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
OG002
Arm 3: Gemcitabine/Nab-paclitaxel
Standard of care chemotherapy in the randomized part
Units
Secondary
Randomized Part: Overall Response Rate (ORR) Per RECIST v1.1
ORR is the percentage of patients with a confirmed best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.
For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Full Analysis Set (FAS)
Posted
Number
95% Confidence Interval
percentage of participants
Up to approximately 1.7 years
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
OG002
Arm 3: Gemcitabine/Nab-paclitaxel
Standard of care chemotherapy in the randomized part
Secondary
Randomized Part: Duration of Response (DOR) Per RECIST v1.1
DOR per RECIST v1.1 is defined as the time from the first documented response of CR or PR to the date of the first documented progression or death. DOR only applies to patients with a best overall response of CR or PR by investigator assessment per RECIST v1.1. Participants continuing without progression or death were censored at the date of their last adequate tumor assessment.
DOR was analyzed using the Kaplan-Meier method.
Participants in the Full Analysis Set (FAS) with CR or PR
Posted
Median
95% Confidence Interval
months
Up to approximately 1.7 years
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
OG002
Arm 3: Gemcitabine/Nab-paclitaxel
Standard of care chemotherapy in the randomized part
Secondary
Randomized Part: Time to Progression (TTP) Per RECIST v1.1
TTP per RECIST v1.1 is defined as the time from the date of randomization to the date of event defined as the first documented progression per RECIST v1.1 or death due to underlying cancer. If a participant had no progression or death, the participant was censored at the date of last adequate tumor assessment.
DOR was analyzed using the Kaplan-Meier method.
Full Analysis Set (FAS)
Posted
Median
95% Confidence Interval
months
Up to approximately 1.7 years
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
OG002
Arm 3: Gemcitabine/Nab-paclitaxel
Standard of care chemotherapy in the randomized part
Secondary
Randomized Part: Overall Survival (OS)
Overall survival is defined as the time from the date of randomization to the date of death due to any cause.
OS was analyzed using the Kaplan-Meier method.
Full Analysis Set (FAS)
Posted
Median
95% Confidence Interval
months
Up to approximately 2 years
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
OG002
Arm 3: Gemcitabine/Nab-paclitaxel
Standard of care chemotherapy in the randomized part
Units
Counts
Participants
Secondary
Randomized Part: Change From Baseline in PD-L1 Expression
The tumor expression of programmed cell death-ligand 1 (PD-L1) was measured by immunohistochemical methods. Results are expressed as absolute change from baseline in PD-L1 expression.
Participants in the Full Analysis Set (FAS) who had a valid assessment of PD-L1 tumor expression at both baseline and on-treatment.
Posted
Mean
Standard Deviation
percentage of PD-L1 positive tumor cells
Baseline (Screening), on-treatment (anytime between Cycle 3 Day 2 and Day 4). The duration of each cycle was 28 days.
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
OG002
Arm 3: Gemcitabine/Nab-paclitaxel
Standard of care chemotherapy in the randomized part
Secondary
Randomized Part: Change From Baseline in CD8 Expression
The tumor expression of CD8 was measured by immunohistochemical methods. Results are expressed as absolute change from baseline in CD8 expression.
Participants in the Full Analysis Set (FAS) who had a valid assessment of CD8 tumor expression at both baseline and on-treatment.
Posted
Mean
Standard Deviation
percentage of CD8 marker area expression
Baseline (Screening), on-treatment (anytime between Cycle 3 Day 2 and Day 4). The duration of each cycle was 28 days.
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
OG002
Arm 3: Gemcitabine/Nab-paclitaxel
Standard of care chemotherapy in the randomized part
Secondary
Randomized Part: Number of Participants With Anti-NIS793 Antibodies
The immunogenicity (IG) against NIS793 was assessed in serum using a validated enhanced electrochemiluminescence immunoassay (ECLIA).
Patient anti-drug antibodies (ADA) status was defined as follows:
ADA-negative at baseline: ADA-negative sample at baseline
ADA-positive at baseline: ADA-positive sample at baseline
ADA-negative post-baseline: patient with ADA-negative sample at baseline and at least 1 post baseline sample, all of which are ADA-negative samples
ADA-inconclusive post-baseline = patient who does not qualify as ADA-positive or ADA-negative post-baseline
Treatment-induced ADA-positive = ADA-negative sample at baseline and at least 1 treatment-induced ADA-positive sample
Participants in the safety set 2 who received NIS793 and had a non-missing baseline ADA sample and at least one non-missing post-baseline ADA sample.
Posted
Count of Participants
Participants
Baseline (before first dose) and post-baseline (assessed throughout the treatment up to approximately 1.7 years)
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
Secondary
Randomized Part: Number of Participants With Anti-spartalizumab Antibodies
The immunogenicity (IG) against spartalizumab was assessed in serum using a validated a validated homogenous enzyme-linked immunosorbent assay (ELISA).
Patient anti-drug antibodies (ADA) status was defined as follows:
ADA-negative at baseline: ADA-negative sample at baseline
ADA-inconclusive at baseline: patient who does not qualify as ADA-positive or ADA-negative at baseline
ADA-positive at baseline: ADA-positive sample at baseline
ADA-negative post-baseline: patient with ADA-negative sample at baseline and at least 1 post baseline sample, all of which are ADA-negative samples
ADA-inconclusive post-baseline = patient who does not qualify as ADA-positive or ADA-negative post-baseline
Treatment-induced ADA-positive = ADA-negative sample at baseline and at least 1 treatment-induced ADA-positive sample
Participants in the safety set 2 who received spartalizumab and had a non-missing baseline ADA sample and at least one non-missing post-baseline ADA sample.
Posted
Count of Participants
Participants
Cycle 1 and Cycle 3. The duration of each cycle was 28 days
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
Units
Counts
Secondary
Randomized Part: Maximum Observed Serum Concentration (Cmax) of NIS793
Pharmacokinetic (PK) parameters were calculated based on NIS793 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed concentration following a dose.
Participants in the pharmacokinetic analysis set (PAS) who received NIS793 and had an available value for the outcome measure. PAS consisted of all patients who received one dose (complete infusion) of the planned treatments and provided at least one valid primary PK parameter.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 and Cycle 3: pre-dose, 1, 24, 168 and 336 hours after the end of the infusion on Day 1. The duration of the infusion was 30 minutes. One cycle=28 days
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
Units
Counts
Secondary
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of NIS793
PK parameters were calculated based on NIS793 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
Participants in the pharmacokinetic analysis set (PAS) who received NIS793 and had an available value for the outcome measure. PAS consisted of all patients who received one dose (complete infusion) of the planned treatments and provided at least one valid primary PK parameter.
Posted
Mean
Standard Deviation
h*ng/mL
Cycle 1 and Cycle 3: pre-dose, 1, 24, 168 and 336 hours after the end of the infusion on Day 1. The duration of the infusion was 30 minutes. One cycle=28 days
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
Units
Counts
Secondary
Randomized Part: Trough Serum Concentration (Ctrough) of NIS793
Ctrough is defined as the concentration reached immediately before the next dose is administered. All drug concentrations below the lower limit of quantification were treated as zero for the calculation of PK parameters.
Participants in the pharmacokinetic analysis set (PAS) who received NIS793 and had an available value for the outcome measure. PAS consisted of all patients who received one dose (complete infusion) of the planned treatments and provided at least one valid primary PK parameter.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1: pre-dose on Day 1. Cycle 3: pre-dose on Day 1 and Day 15 (combined). One cycle=28 days
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
Units
Counts
Participants
Secondary
Randomized Part: Maximum Observed Serum Concentration (Cmax) of Spartalizumab
PK parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed concentration following a dose.
Participants in the pharmacokinetic analysis set (PAS) who received spartalizumab and had an available value for the outcome measure. PAS consisted of all patients who received one dose (complete infusion) of the planned treatments and provided at least one valid primary PK parameter.
Posted
Mean
Standard Deviation
µg/mL
Cycle 1 and Cycle 3: pre-dose, 1, 24, 168 and 648 hours after the end of the infusion on Day 1. The duration of the infusion was 30 minutes. One cycle=28 days
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
Units
Counts
Participants
OG000
Secondary
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Spartalizumab
PK parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
Participants in the pharmacokinetic analysis set (PAS) who received spartalizumab and had an available value for the outcome measure. PAS consisted of all patients who received one dose (complete infusion) of the planned treatments and provided at least one valid primary PK parameter.
Posted
Mean
Standard Deviation
h*µg/mL
Cycle 1 and Cycle 3: pre-dose, 1, 24, 168 and 648 hours after the end of the infusion on Day 1. The duration of the infusion was 30 minutes. One cycle=28 days
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
Units
Counts
Participants
OG000
Secondary
Randomized Part: Trough Serum Concentration (Ctrough) of Spartalizumab
Ctrough is defined as the concentration reached immediately before the next dose is administered. All drug concentrations below the lower limit of quantification were treated as zero for the calculation of PK parameters.
Participants in the pharmacokinetic analysis set (PAS) who received spartalizumab and had an available value for the outcome measure. PAS consisted of all patients who received one dose (complete infusion) of the planned treatments and provided at least one valid primary PK parameter.
Posted
Mean
Standard Deviation
µg/mL
Cycle 2, 3 and 4: pre-dose on Day 1. One cycle=28 days
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
Units
Counts
Participants
OG000
Secondary
Randomized Part: Maximum Observed Plasma Concentration (Cmax) of Gemcitabine
PK parameters were calculated based on gemcitabine plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed concentration following a dose.
Participants in the pharmacokinetic analysis set (PAS) who received gemcitabine and had an available value for the outcome measure. PAS consisted of all patients who received one dose (complete infusion) of the planned treatments and provided at least one valid primary PK parameter.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 and Cycle 4: pre-dose, end of infusion, and 2, 3, 5 and 24 hours after the start of infusion on Day 1. The duration of the infusion was according to the product labelling and local guidance. One cycle=28 days
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
OG002
Arm 3: Gemcitabine/Nab-paclitaxel
Secondary
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Gemcitabine
PK parameters were calculated based on gemcitabine plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
Participants in the pharmacokinetic analysis set (PAS) who received gemcitabine and had an available value for the outcome measure. PAS consisted of all patients who received one dose (complete infusion) of the planned treatments and provided at least one valid primary PK parameter.
Posted
Mean
Standard Deviation
h*ng/mL
Cycle 1 and Cycle 4: pre-dose, end of infusion, and 2, 3, 5 and 24 hours after the start of infusion on Day 1. The duration of the infusion was according to the product labelling and local guidance. One cycle=28 days
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
OG002
Arm 3: Gemcitabine/Nab-paclitaxel
Secondary
Randomized Part: Trough Serum Concentration (Ctrough) of Gemcitabine
Ctrough is defined as the concentration reached immediately before the next dose is administered. All drug concentrations below the lower limit of quantification were treated as zero for the calculation of PK parameters.
Participants in the pharmacokinetic analysis set (PAS) who received gemcitabine and had an available value for the outcome measure. PAS consisted of all patients who received one dose (complete infusion) of the planned treatments and provided at least one valid primary PK parameter.
Posted
Mean
Standard Deviation
ng/mL
Cycle 4: pre-dose on Day 1. One cycle=28 days
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
OG002
Arm 3: Gemcitabine/Nab-paclitaxel
Standard of care chemotherapy in the randomized part
Secondary
Randomized Part: Maximum Observed Plasma Concentration (Cmax) of Nab-paclitaxel
PK parameters were calculated based on nab-paclitaxel plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed concentration following a dose.
Participants in the pharmacokinetic analysis set (PAS) who received nab-paclitaxel and had an available value for the outcome measure. PAS consisted of all patients who received one dose (complete infusion) of the planned treatments and provided at least one valid primary PK parameter.
Posted
Mean
Standard Deviation
ng/mL
Cycle 1 and Cycle 4: pre-dose, end of infusion, and 2, 3, 5 and 24 hours after the start of infusion on Day 1. The duration of the infusion was according to the product labelling and local guidance. One cycle=28 days
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
OG002
Arm 3: Gemcitabine/Nab-paclitaxel
Secondary
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Nab-paclitaxel
PK parameters were calculated based on nab-paclitaxel plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
Participants in the pharmacokinetic analysis set (PAS) who received nab-paclitaxel and had an available value for the outcome measure. PAS consisted of all patients who received one dose (complete infusion) of the planned treatments and provided at least one valid primary PK parameter.
Posted
Mean
Standard Deviation
h*ng/mL
Cycle 1 and Cycle 4: pre-dose, end of infusion, and 2, 3, 5 and 24 hours after the start of infusion on Day 1. The duration of the infusion was according to the product labelling and local guidance. One cycle=28 days
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
OG002
Arm 3: Gemcitabine/Nab-paclitaxel
Secondary
Randomized Part: Trough Serum Concentration (Ctrough) of Nab-paclitaxel
Ctrough is defined as the concentration reached immediately before the next dose is administered. All drug concentrations below the lower limit of quantification were treated as zero for the calculation of PK parameters.
Participants in the pharmacokinetic analysis set (PAS) who received nab-paclitaxel and had an available value for the outcome measure. PAS consisted of all patients who received one dose (complete infusion) of the planned treatments and provided at least one valid primary PK parameter.
Posted
Mean
Standard Deviation
ng/mL
Cycle 4: pre-dose on Day 1. One cycle=28 days
ID
Title
Description
OG000
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
OG001
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with standard of care chemotherapy in the randomized part
OG002
Arm 3: Gemcitabine/Nab-paclitaxel
Standard of care chemotherapy in the randomized part
Post-Hoc
All-Collected Deaths
On-treatment and post-treatment safety follow-up (FU) deaths were collected from first dose of study treatment to 90 days after last dose of NIS793, 150 days after last dose of spartalizumab and 30 days after last dose of gemcitabine and nab-paclitaxel, whichever was longer.
Survival FU deaths were collected from 91 days after last dose of NIS793, 151 days after last dose of spartalizumab and 31 days after last dose of gemcitabine and nab-paclitaxel, whichever was longer, until end of study.
All deaths refer to the sum of pre-treatment deaths, on-treatment and post-treatment safety FU deaths, and survival FU deaths.
Safety set 1 (safety run-in) and Full Analysis Set (randomized part)
Posted
Number
Participants
On-treatment and post-treatment safety FU deaths: up to approximately 1 year (run-in part) and 1.9 years (randomized part). Survival FU deaths: up to approximately 1.8 years (run-in part) and 2 years (randomized part)
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the safety run-in part
OG001
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel
NIS793 2100 mg every 2 weeks i.v. with spartalizumab 400 mg every 4 weeks i.v and standard of care chemotherapy in the randomized part
Time Frame
On- and post-treatment safety FU: from first dose of study treatment to 90 days after last dose of NIS793, 150 days after last dose of spartalizumab and 30 days after last dose of gemcitabine and nab-paclitaxel, whichever was longer, up to approx. 1 year (run-in part) and 1.9 years (randomized part). Deaths in survival period: after completing safety FU until end of study, up to approx. 1.8 years (run-in part) and 2 years (randomized part).
Description
Deaths in the survival period are not considered Adverse Events (AEs). No AEs were collected in the survival period. Deaths were assessed in the Safety set 1 (run-in part) and Full Analysis Set (randomized part). AEs were assessed in the Safety set 1 (run-in part) and Safety set 2 (randomized part).
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Run-in: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel_On- and Post-treatment
Safety data up to 90 days after last dose of NIS793, 150 days after last dose of spartalizumab and 30 days after last dose of gemcitabine and nab-paclitaxel, whichever was longer
5
11
8
11
11
11
EG001
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel_On- and Post-treatment
Safety data up to 90 days after last dose of NIS793, 150 days after last dose of spartalizumab and 30 days after last dose of gemcitabine and nab-paclitaxel, whichever was longer
18
50
34
46
45
46
EG002
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel_On- and Post-treatment
Safety data up to 90 days after last dose of NIS793 and 30 days after last dose of gemcitabine and nab-paclitaxel, whichever was longer
19
51
28
49
48
49
EG003
Arm 3: Gemcitabine/Nab-paclitaxel_On- and Post-treatment
Safety data up to 30 days after last dose of gemcitabine and nab-paclitaxel
4
52
26
45
40
45
EG004
All Participants_On- and Post-treatment
Safety data up to 90 days after last dose of NIS793, 150 days after last dose of spartalizumab and 30 days after last dose of gemcitabine and nab-paclitaxel, whichever was longer
46
164
96
151
144
151
EG005
Run-in: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel_Survival Period
Deaths collected in the survival follow-up period (starting from Day 90 after last dose of NIS793, Day 151 days after last dose of spartalizumab and Day 31 after last dose of gemcitabine and nab-paclitaxel, whichever was longer). No AEs were collected during this period.
5
6
0
0
0
0
EG006
Arm 1: NIS793 + Spartalizumab + Gemcitabine/Nab-paclitaxel_Survival Period
Deaths collected in the survival follow-up period (starting from Day 90 after last dose of NIS793, Day 151 days after last dose of spartalizumab and Day 31 after last dose of gemcitabine and nab-paclitaxel, whichever was longer). No AEs were collected during this period.
15
28
0
0
0
0
EG007
Arm 2: NIS793 + Gemcitabine/Nab-paclitaxel_Survival Period
Deaths collected in the survival follow-up period (starting from Day 90 after last dose of NIS793 and Day 31 after last dose of gemcitabine and nab-paclitaxel, whichever was longer). No AEs were collected during this period.
22
30
0
0
0
0
EG008
Arm 3: Gemcitabine/Nab-paclitaxel_Survival Period
Deaths collected in the survival follow-up period (starting from Day 31 after last dose of gemcitabine and nab-paclitaxel). No AEs were collected during this period.
35
41
0
0
0
0
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0012 affected46 at risk
EG0026 affected49 at risk
EG0032 affected45 at risk
EG00410 affected151 at risk
EG0050 at risk
EG0060 at risk
EG0070 at risk
EG0080 at risk
Blood loss anaemia
Blood and lymphatic system disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0012 affected46 at risk
EG0021 affected49 at risk
EG003
Haemolysis
Blood and lymphatic system disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Haemolytic uraemic syndrome
Blood and lymphatic system disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Pericardial effusion
Cardiac disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Supraventricular tachycardia
Cardiac disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Glucocorticoid deficiency
Endocrine disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Hypopituitarism
Endocrine disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0012 affected46 at risk
EG0020 affected49 at risk
EG003
Abdominal pain lower
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Colitis
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0012 affected46 at risk
EG0021 affected49 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0015 affected46 at risk
EG0020 affected49 at risk
EG003
Diarrhoea haemorrhagic
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Duodenal obstruction
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Duodenal perforation
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Enterocolitis
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Gastric haemorrhage
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Gastritis haemorrhagic
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Gastrointestinal pain
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Gastrointestinal toxicity
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Haematemesis
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Ileus
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Immune-mediated enterocolitis
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Impaired gastric emptying
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Melaena
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0022 affected49 at risk
EG003
Small intestinal haemorrhage
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Small intestinal obstruction
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Subileus
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0022 affected49 at risk
EG003
Upper gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0022 affected49 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Asthenia
General disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Chest pain
General disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Chills
General disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Fatigue
General disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0013 affected46 at risk
EG0020 affected49 at risk
EG003
Gait inability
General disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
General physical health deterioration
General disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Pain
General disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0011 affected46 at risk
EG0021 affected49 at risk
EG003
Pyrexia
General disorders
MedDRA (27.0)
Systematic Assessment
EG0002 affected11 at risk
EG0015 affected46 at risk
EG0023 affected49 at risk
EG003
Biliary obstruction
Hepatobiliary disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0022 affected49 at risk
EG003
Cholangitis
Hepatobiliary disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0012 affected46 at risk
EG0022 affected49 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Cholecystitis acute
Hepatobiliary disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Gallbladder rupture
Hepatobiliary disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Hepatic failure
Hepatobiliary disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Hepatitis
Hepatobiliary disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Hypertransaminasaemia
Hepatobiliary disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Immune-mediated hepatitis
Hepatobiliary disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Abdominal infection
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Acarodermatitis
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Anal abscess
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Bacteraemia
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Biliary sepsis
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Biliary tract infection
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0021 affected49 at risk
EG003
COVID-19
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
COVID-19 pneumonia
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Campylobacter infection
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Device related infection
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0023 affected49 at risk
EG003
Febrile infection
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0022 affected49 at risk
EG003
Infection
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0013 affected46 at risk
EG0021 affected49 at risk
EG003
Large intestine infection
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0014 affected46 at risk
EG0020 affected49 at risk
EG003
Pneumonia bacterial
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Pneumonia pseudomonal
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Postoperative wound infection
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Relapsing fever
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Sepsis
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0014 affected46 at risk
EG0023 affected49 at risk
EG003
Septic shock
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Acetabulum fracture
Injury, poisoning and procedural complications
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Craniofacial fracture
Injury, poisoning and procedural complications
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0021 affected49 at risk
EG003
Femur fracture
Injury, poisoning and procedural complications
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Head injury
Injury, poisoning and procedural complications
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Infusion related reaction
Injury, poisoning and procedural complications
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Scapula fracture
Injury, poisoning and procedural complications
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Spinal fracture
Injury, poisoning and procedural complications
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
General physical condition abnormal
Investigations
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Myocardial necrosis marker increased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0022 affected49 at risk
EG003
Diabetic ketoacidosis
Metabolism and nutrition disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Degenerative bone disease
Musculoskeletal and connective tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Squamous cell carcinoma of skin
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0021 affected49 at risk
EG003
Tumour obstruction
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Demyelinating polyneuropathy
Nervous system disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Hepatic encephalopathy
Nervous system disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Syncope
Nervous system disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0021 affected49 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0013 affected46 at risk
EG0021 affected49 at risk
EG003
Bladder tamponade
Renal and urinary disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Proteinuria
Renal and urinary disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Renal failure
Renal and urinary disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Orchitis noninfective
Reproductive system and breast disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0022 affected49 at risk
EG003
Interstitial lung disease
Respiratory, thoracic and mediastinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Pneumomediastinum
Respiratory, thoracic and mediastinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Pneumothorax
Respiratory, thoracic and mediastinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0022 affected49 at risk
EG003
Pulmonary fibrosis
Respiratory, thoracic and mediastinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Pulmonary oedema
Respiratory, thoracic and mediastinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Hypotension
Vascular disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0022 affected49 at risk
EG003
Venous thrombosis
Vascular disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (27.0)
Systematic Assessment
EG0005 affected11 at risk
EG00129 affected46 at risk
EG00233 affected49 at risk
EG00320 affected45 at risk
EG00487 affected151 at risk
EG0050 at risk
EG0060 at risk
EG0070 at risk
EG0080 at risk
Leukocytosis
Blood and lymphatic system disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0013 affected46 at risk
EG0020 affected49 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0014 affected46 at risk
EG0022 affected49 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (27.0)
Systematic Assessment
EG0005 affected11 at risk
EG00111 affected46 at risk
EG0029 affected49 at risk
EG003
Neutrophilia
Blood and lymphatic system disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA (27.0)
Systematic Assessment
EG0002 affected11 at risk
EG0017 affected46 at risk
EG0024 affected49 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0023 affected49 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0014 affected46 at risk
EG0029 affected49 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0014 affected46 at risk
EG0028 affected49 at risk
EG003
Aphthous ulcer
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG00116 affected46 at risk
EG00216 affected49 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0005 affected11 at risk
EG00126 affected46 at risk
EG00219 affected49 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0024 affected49 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0002 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0025 affected49 at risk
EG003
Gingival bleeding
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0002 affected11 at risk
EG0011 affected46 at risk
EG0026 affected49 at risk
EG003
Gingival hypertrophy
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Gingival swelling
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0002 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Haemorrhoids
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0011 affected46 at risk
EG0023 affected49 at risk
EG003
Ileal perforation
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Ileus
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0007 affected11 at risk
EG00120 affected46 at risk
EG00227 affected49 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0024 affected49 at risk
EG003
Tongue coated
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Tongue disorder
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (27.0)
Systematic Assessment
EG0003 affected11 at risk
EG00110 affected46 at risk
EG00218 affected49 at risk
EG003
Asthenia
General disorders
MedDRA (27.0)
Systematic Assessment
EG0005 affected11 at risk
EG00112 affected46 at risk
EG00216 affected49 at risk
EG003
Chills
General disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0013 affected46 at risk
EG0022 affected49 at risk
EG003
Fatigue
General disorders
MedDRA (27.0)
Systematic Assessment
EG0007 affected11 at risk
EG00123 affected46 at risk
EG00218 affected49 at risk
EG003
Mucosal inflammation
General disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0015 affected46 at risk
EG0024 affected49 at risk
EG003
Oedema
General disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0013 affected46 at risk
EG0020 affected49 at risk
EG003
Oedema peripheral
General disorders
MedDRA (27.0)
Systematic Assessment
EG0004 affected11 at risk
EG00111 affected46 at risk
EG00215 affected49 at risk
EG003
Pain
General disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0012 affected46 at risk
EG0021 affected49 at risk
EG003
Pyrexia
General disorders
MedDRA (27.0)
Systematic Assessment
EG0007 affected11 at risk
EG00119 affected46 at risk
EG00211 affected49 at risk
EG003
Hepatobiliary disease
Hepatobiliary disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Immune-mediated hepatitis
Hepatobiliary disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
COVID-19
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG00113 affected46 at risk
EG0026 affected49 at risk
EG003
Infection
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0012 affected46 at risk
EG0020 affected49 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0022 affected49 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0017 affected46 at risk
EG0026 affected49 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0011 affected46 at risk
EG0021 affected49 at risk
EG003
Infusion related reaction
Injury, poisoning and procedural complications
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0012 affected46 at risk
EG0020 affected49 at risk
EG003
Wound dehiscence
Injury, poisoning and procedural complications
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0021 affected49 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0004 affected11 at risk
EG00114 affected46 at risk
EG00210 affected49 at risk
EG003
Amylase increased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0015 affected46 at risk
EG0022 affected49 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0004 affected11 at risk
EG00113 affected46 at risk
EG0029 affected49 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0002 affected11 at risk
EG0014 affected46 at risk
EG0022 affected49 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0025 affected49 at risk
EG003
Blood creatinine increased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0013 affected46 at risk
EG0021 affected49 at risk
EG003
Blood lactate dehydrogenase increased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0012 affected46 at risk
EG0023 affected49 at risk
EG003
C-reactive protein increased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0014 affected46 at risk
EG0022 affected49 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0004 affected11 at risk
EG0011 affected46 at risk
EG0021 affected49 at risk
EG003
Lipase increased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0002 affected11 at risk
EG0015 affected46 at risk
EG0023 affected49 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0002 affected11 at risk
EG0017 affected46 at risk
EG0028 affected49 at risk
EG003
Platelet count decreased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0018 affected46 at risk
EG00210 affected49 at risk
EG003
Tri-iodothyronine decreased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Weight decreased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0002 affected11 at risk
EG0012 affected46 at risk
EG0026 affected49 at risk
EG003
White blood cell count decreased
Investigations
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0013 affected46 at risk
EG0023 affected49 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (27.0)
Systematic Assessment
EG0004 affected11 at risk
EG00110 affected46 at risk
EG00217 affected49 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0014 affected46 at risk
EG0021 affected49 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA (27.0)
Systematic Assessment
EG0002 affected11 at risk
EG0011 affected46 at risk
EG0021 affected49 at risk
EG003
Hypochloraemia
Metabolism and nutrition disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0018 affected46 at risk
EG0026 affected49 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0014 affected46 at risk
EG0022 affected49 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0011 affected46 at risk
EG0022 affected49 at risk
EG003
Hypophosphataemia
Metabolism and nutrition disorders
MedDRA (27.0)
Systematic Assessment
EG0003 affected11 at risk
EG0019 affected46 at risk
EG0027 affected49 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0014 affected46 at risk
EG0025 affected49 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0016 affected46 at risk
EG0025 affected49 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0013 affected46 at risk
EG0021 affected49 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0011 affected46 at risk
EG0021 affected49 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0025 affected49 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0023 affected49 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0016 affected46 at risk
EG0025 affected49 at risk
EG003
Headache
Nervous system disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0012 affected46 at risk
EG0021 affected49 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0013 affected46 at risk
EG0023 affected49 at risk
EG003
Neuropathy peripheral
Nervous system disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0015 affected46 at risk
EG00211 affected49 at risk
EG003
Neurotoxicity
Nervous system disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0011 affected46 at risk
EG0020 affected49 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA (27.0)
Systematic Assessment
EG0002 affected11 at risk
EG0014 affected46 at risk
EG0023 affected49 at risk
EG003
Peripheral sensory neuropathy
Nervous system disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0014 affected46 at risk
EG0022 affected49 at risk
EG003
Polyneuropathy
Nervous system disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0015 affected46 at risk
EG0025 affected49 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0013 affected46 at risk
EG0024 affected49 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0014 affected46 at risk
EG0023 affected49 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0013 affected46 at risk
EG0021 affected49 at risk
EG003
Prostatomegaly
Reproductive system and breast disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0013 affected46 at risk
EG00211 affected49 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0011 affected46 at risk
EG0028 affected49 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA (27.0)
Systematic Assessment
EG0002 affected11 at risk
EG00111 affected46 at risk
EG00214 affected49 at risk
EG003
Nasal dryness
Respiratory, thoracic and mediastinal disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0010 affected46 at risk
EG0023 affected49 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0014 affected46 at risk
EG0023 affected49 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0003 affected11 at risk
EG00111 affected46 at risk
EG00215 affected49 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0013 affected46 at risk
EG0023 affected49 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0014 affected46 at risk
EG0023 affected49 at risk
EG003
Night sweats
Skin and subcutaneous tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0022 affected49 at risk
EG003
Onycholysis
Skin and subcutaneous tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0002 affected11 at risk
EG00114 affected46 at risk
EG0028 affected49 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0006 affected11 at risk
EG00113 affected46 at risk
EG00218 affected49 at risk
EG003
Rash macular
Skin and subcutaneous tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0002 affected11 at risk
EG00110 affected46 at risk
EG0021 affected49 at risk
EG003
Skin toxicity
Skin and subcutaneous tissue disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0012 affected46 at risk
EG0022 affected49 at risk
EG003
Hypertension
Vascular disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0013 affected46 at risk
EG0024 affected49 at risk
EG003
Hypotension
Vascular disorders
MedDRA (27.0)
Systematic Assessment
EG0000 affected11 at risk
EG0014 affected46 at risk
EG0026 affected49 at risk
EG003
Jugular vein thrombosis
Vascular disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Vein rupture
Vascular disorders
MedDRA (27.0)
Systematic Assessment
EG0001 affected11 at risk
EG0010 affected46 at risk
EG0020 affected49 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The terms and conditions of Novartis' agreements with its investigators may vary. Novartis does not prohibit any investigator from publishing. Any publications from a single site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.