Phase III Study Evaluating Efficacy and Safety of Canakin... | NCT03626545 | Trialant
NCT03626545
Sponsor
Novartis Pharmaceuticals
Status
Terminated
Last Update Posted
Aug 21, 2023Actual
Enrollment
245Actual
Phase
Phase 3
Conditions
Non-Small-Cell Lung
Interventions
Canakinumab
Docetaxel
Placebo
Countries
United States
Argentina
Australia
Belgium
Brazil
Canada
Chile
China
Czechia
Denmark
France
Germany
Greece
Hungary
Israel
Italy
Japan
Jordan
Lebanon
Netherlands
Poland
Russia
Singapore
South Korea
Spain
Taiwan
Protocol Section
Identification Module
NCT ID
NCT03626545
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CACZ885V2301
Secondary IDs
ID
Type
Description
Link
2018-002480-26
EudraCT Number
Brief Title
Phase III Study Evaluating Efficacy and Safety of Canakinumab in Combination With Docetaxel in Adult Subjects With Non-small Cell Lung Cancers as a Second or Third Line Therapy
Official Title
A Randomized, Double-blind, Placebo-controlled, Phase III Study Evaluating the Efficacy and Safety of Canakinumab in Combination With Docetaxel Versus Placebo in Combination With Docetaxel in Adult Subjects With Non-small Cell Lung Cancer (NSCLC) Previously Treated With PD-(L)1 Inhibitors and Platinum-based Chemotherapy (CANOPY 2)
Acronym
CANOPY-2
Organization
NovartisINDUSTRY
Status Module
Record Verification Date
Aug 2023
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
The study was early terminated due to the lack of efficacy of study treatment observed in the analysis of the primary endpoint of the randomized part
Expanded Access Info
No
Start Date
Jan 23, 2019Actual
Primary Completion Date
Jan 8, 2021Actual
Completion Date
Dec 20, 2021Actual
First Submitted Date
Jul 25, 2018
First Submission Date that Met QC Criteria
Aug 8, 2018
First Posted Date
Aug 13, 2018Actual
Results Waived
Not provided
Results First Submitted Date
Sep 2, 2022
Results First Submitted that Met QC Criteria
Jun 20, 2023
Results First Posted Date
Jun 22, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Dec 1, 2021
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Jun 22, 2023Actual
Last Update Submitted Date
Aug 16, 2023
Last Update Posted Date
Aug 21, 2023Actual
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
This study was designed to evaluate the role of canakinumab in combination with docetaxel in subjects with advanced non-small cell lung cancer (NSCLC) previously treated with PD-(L)1 inhibitors and platinum-based chemotherapy.
Detailed Description
This was a multicenter, Phase III study designed to evaluate the efficacy and safety of canakinumab in combination with docetaxel versus placebo in combination with docetaxel, as second- or third-line treatment. The study included adult subjects with advanced NSCLC whose disease had progressed after prior treatment with a PD-(L)1 inhibitor. Subjects had also been pre-treated with platinum-based chemotherapy, either given together with PD-(L)1 inhibitor or sequentially.
The study consisted of 2 parts:
Part 1: Safety run-in. This part was conducted to confirm the Recommended Phase 3 Regimen (RP3R) of the canakinumab and docetaxel combination. Participants were treated for at least 2 complete cycles of treatment (21 days per cycle) for safety evaluation (DLT-Dose Limiting Toxicities) to define RP3R. Participants from the safety run-in part were treated until any discontinuation criteria were met. After treatment discontinuation, all participants were followed for safety evaluations during the safety follow up period (up to 130 days). Additionally, subjects who discontinued study treatment without prior documented disease progression continued efficacy assessments in the efficacy follow-up phase irrespective of the start of new antineoplastic therapy and until documented progressive disease as per protocol. After the RP3R was determined, enrollment in this part was closed and additional participants were enrolled in the randomized part (part 2) of the study. Ongoing patients from the safety run-in part continued their treatment at the assigned dose level according to the dose and schedule for the safety run-in part.
Part 2: Randomized part. The randomized, double-blind, placebo-controlled part of the study opened after confirmation of the RP3R for the combination of canakinumab and docetaxel. Participants from the randomized part were treated until any discontinuation criteria were met as per protocol. After treatment discontinuation, all participants were followed for safety evaluations during the safety follow up period (up to 130 days). Additionally, subjects who discontinued study treatment without prior documented disease progression continued efficacy assessments in the efficacy follow-up phase irrespective of the start of new antineoplastic therapy and until documented progressive disease as per protocol.
Based on the lack of efficacy observed in the primary analysis, Novartis decided to halt canakinumab/placebo treatment. Subjects continued to receive docetaxel if they were deriving clinical benefit as per investigator assessment until discontinuation
Conditions Module
Conditions
Non-Small-Cell Lung
Keywords
ACZ885
canakinumab
docetaxel
NSCLC
Non Small Cell Lung Cancer
Carcinoma
IL-1β
PD-(L)1
CANOPY
CANOPY-2
second or third line therapy
PD-(L)1 inhibitors
platinum-based chemotherapy
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 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
245Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Safety run-in part: Canakinumab+docetaxel
Experimental
Participants were treated with full doses of docetaxel 75mg/m^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1). Subjects were assessed for at least 2 complete cycles of treatment (21 days per cycle; a total of 42 days) for safety evaluation (DLT) to define RP3R. De-escalation to canakinumab 200 mg subcutaneous every 6 weeks + docetaxel 75 mg/m^2, every 3 weeks could also be considered.
Drug: Canakinumab
Drug: Docetaxel
Randomized part: Canakinumab + docetaxel
Experimental
Participants were treated with canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 every 3 weeks
Drug: Canakinumab
Drug: Docetaxel
Randomized part: Placebo + docetaxel
Placebo Comparator
Participants were treated with placebo subcutaneous at RP3R and docetaxel at 75 mg/m^2 every 3 weeks
Drug: Docetaxel
Other: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Canakinumab
Drug
Canakinumab, 200 mg, subcutaneous. The initial dose regimen was once every 3 weeks (on Day 1 of each 21-day cycle)
Randomized part: Canakinumab + docetaxel
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Safety run-in Part: Percentage of Participants With Dose Limiting Toxicities (DLTs)
Percentage of participants with DLTs. A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 42 days of docetaxel and canakinumab treatment.
During the first 42 days of dosing
Randomized Part: Overall Survival (OS)
OS is defined as the time from randomization to date of death due to any cause. The OS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated for each treatment group. If a subject was not known to have died, then OS was censored at the latest date the subject was known to be alive (on or before the cut-off date).
From randomization until death or final analysis data cutoff date (08-Jan-2021) whichever comes first (up to approximately (approx.) 18 months)
Secondary Outcomes
Measure
Description
Time Frame
Overall Response Rate (ORR)
ORR is defined as the percentage of participants with confirmed best overall response of complete response (CR) or partial response (PR), as per investigator's assessment by RECIST 1.1. The 95% confidence intervals (CIs) were computed using Clopper and Pearson method.
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.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Key Inclusion Criteria:
Histologically confirmed advanced (stage IIIB) or metastatic NSCLC.
Subject had received one prior platinum-based chemotherapy and one prior PD-(L)1 inhibitor therapy for locally advanced or metastatic disease.
Subject with ECOG performance status (PS) of 0 or 1.
Subject with at least 1 evaluable (measurable or non-measurable) lesion by RECIST 1.1 in solid tumors criteria.
Key Exclusion Criteria:
Subject who previously received docetaxel, canakinumab (or another IL-1β inhibitor), or any systemic therapy for their locally advanced or metastatic NSCLC other than one platinum-based chemotherapy and one prior PD-(L)1 inhibitor.
Subject with EGFRor ALK positive tumor.
History of severe hypersensitivity reaction to monoclonal antibodies, taxanes or excipients of docetaxel or canakinumab.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Emory Winship Cancer Institute
Atlanta
Georgia
30322
United States
Saint Luke's Hospital/Marion Bloch Neuroscience Institute Dept of Regulatory
Paz-Ares L, Goto Y, Wan-Teck Lim D, Halmos B, Chul Cho B, Cobo M, Luis Gonzalez Larriba J, Zhou C, Demedts I, Atmaca A, Baka S, Mookerjee B, Portella S, Zhu Z, Wu J, Demanse D, Dharan B, Reck M. Canakinumab in combination with docetaxel compared with docetaxel alone for the treatment of advanced non-small cell lung cancer following platinum-based doublet chemotherapy and immunotherapy (CANOPY-2): A multicenter, randomized, double-blind, phase 3 trial. Lung Cancer. 2024 Mar;189:107451. doi: 10.1016/j.lungcan.2023.107451. Epub 2024 Jan 16.
See Also Links
Label
URL
A Plain Language Trial Summary is available on 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 expert 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.
In the randomized part, a total of 352 subjects were screened. 237 subjects completed the screening phase and were randomized in a 1:1 ratio to treatment with either canakinumab plus docetaxel or placebo plus docetaxel. Three randomized subjects in the placebo plus docetaxel group were not treated
Recruitment Details
The Safety run-in (Part 1) was conducted in 6 centers across 4 countries and the Randomized part (Part 2) was conducted in 85 centers across 26 countries.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Safety run-in Part: Canakinumab+Docetaxel
Participants were treated with full doses of docetaxel 75mg/m^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1).
Docetaxel 75mg/m^2, intravenous, administered on Day 1 of each 21-day cycle
Randomized part: Canakinumab + docetaxel
Randomized part: Placebo + docetaxel
Safety run-in part: Canakinumab+docetaxel
Placebo
Other
Placebo, sub-cutaneous, admnistered at the RP3R defined in Part 1-safety run-in.
Randomized part: Placebo + docetaxel
Through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 10 months for the safety run-in part and 18 months for the randomized part)
Duration of Response (DOR)
DOR is defined as the time from first documented response of CR or PR to date of first documented progression or death, by investigator's assessment according to RECIST 1.1 criteria. The DOR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated for each treatment group.
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.
From first documented response of CR or PR to date of first documented progression, death or final analysis data cutoff date (08-Jan-2021) whichever comes first (up to approx. 10 months for the safety run-in and 18 months for the randomized)
Disease Control Rate (DCR)
DCR is defined as the percentage of participants with CR or PR or with stable disease (SD) as per investigator assessment according to RECIST 1.1 criteria. The 95% CIs were computed using Clopper and Pearson method.
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.
SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 10 months for the safety run-in part and 18 months for the randomized part)
Randomized Part: Progression-Free Survival (PFS)
PFS is defined as the time from randomization to the date of the first documented radiological progression by investigator assessment according to RECIST 1.1 response criteria or death due to any cause.
The PFS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated for each treatment group. If a participant did not have disease progression or die at the analysis cut-off date, PFS was censored at the date of last adequate tumor assessment.
From randomization until disease progression, death or final analysis data cutoff date (08-Jan-2021) whichever comes first (assessed up to approx. 18 months)
Randomized Part: Time to Response (TTR)
TTR is defined as the time from the date of randomization to the date of first documented response of either CR or PR, by investigator's assessment according to RECIST 1.1 criteria. The TTR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated for each treatment group. Subjects without a confirmed CR or PR at the time of the analysis cut-off date were censored at the study-maximum follow-up time for subjects with a PFS event (i.e., disease progression or death due to any cause), or at the date of the last adequate tumor assessment for subjects without a PFS event.
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.
From randomization until first documented response or final analysis data cutoff date (08-Jan-2021) whichever comes first (up to approx. 18 months)
Randomized Part: Time to Definitive 10-point Deterioration (TTD) Symptom Scores of Chest Pain, Cough and Dyspnea Per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) Lung Cancer (LC13) Questionnaire
The EORTC QLQ-LC13 comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, dyspnea, and chest pain) and treatment-related symptoms from conventional chemotherapy and radiotherapy (ie. hair loss, neuropathy, sore mouth, and dysphagia). Scores for each scale and single-item range from 0 to 100, with higher scores indicating higher level of symptoms. TTD for chest pain, cough and dyspnea is defined as the time from randomization to the date of event, which is defined as at least 10 points absolute worsening from baseline of the corresponding scale score, with no later change below this threshold ie.<10 points was observed or if this worsening was observed at the last assessment for the subject, or death due to any cause (whichever occurs earlier). If a subject did not have an event, TTD was censored at the last adequate assessment.
From baseline through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 18 months)
Randomized Part: Time to Definitive 10-point Deterioration in Global Health Status (GHS)/Quality of Life (QoL), Shortness of Breath and Pain Per EORTC QLQ-C30 Questionnaire
The EORTC QLQ-C30 includes 5 functional scales (physical,role,cognitive,emotional and social), 3 symptom scales (fatigue,pain and nausea/vomiting), a GHS/QoL scale, and 6 single items (constipation,diarrhea,insomnia,shortness of breath,appetite loss and financial difficulties). For each scale and single-item, scores range between 0 and 100. A high score for functional scales/ GHS/QoL represents better functioning or QoL, a high score for symptom scales/single items represents significant symptomatology. TTD in GHS/QoL, shortness of breath and pain is defined as the time from randomization to the date of event, defined as at least 10 points absolute worsening from baseline of the corresponding scale score, with no later change below this threshold i.e.<10 points was observed or if this worsening was observed at the last assessment for the subject, or death due to any cause (whichever occurs earlier). If a subject did not have an event, TTD was censored at the last adequate assessment.
From baseline through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 18 months)
Randomized Part: Change From Baseline in GHS/QoL, Shortness of Breath and Pain Scores as Per the EORTC QLQ C30 Questionnaire
The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/QoL scale, and 6 single items (constipation, diarrhea, insomnia, dyspnoea, appetite loss and financial difficulties). For each scale and item, scores range 0-100. A high score for functional scales/QoL represents better functioning/QoL; a high score for symptom scales and items represents significant symptomatology. Changes from baseline in QoL, shortness of breath and pain scores are presented. For QoL, a negative change from baseline indicates improvement; for shortness of breath and pain a positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits 1, 2, 3 and 5 were conducted every 6 weeks (for the first 12 months since start of treatment) and every 12 weeks (after 12 months since start of treatment) until disease progression
Baseline, every 3 weeks from Week 3 until end of treatment, every 6 or 12 weeks post-treatment until progression (post-treatment efficacy visits), 7 and 28 days post progression through final analysis cutoff date of 08Jan2021 (up to approx. 18 months)
Randomized Part: Change From Baseline in Chest Pain, Cough and Dyspnea Scores as Per the EORTC-QLQ LC13 Questionnaire
The EORTC QLQ-LC13 is a 13-item questionnaire. It comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, dyspnea, and chest pain) and treatment-related symptoms from conventional chemotherapy and radiotherapy (ie, hair loss, neuropathy, sore mouth, and dysphagia). Scores for each scale and single-item range from 0 to 100, with higher scores indicating higher ("worse") level of symptoms. Changes from baseline in chest pain, cough and dyspnea scores are presented. A positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits 1, 2, 3 and 5 were conducted every 6 weeks (for the first 12 months since start of treatment) and every 12 weeks (after 12 months since start of treatment) until disease progression
Baseline, every 3 weeks from Week 3 until end of treatment, every 6 or 12 weeks post-treatment until progression (post-treatment efficacy visits), 7 and 28 days post progression through final analysis cutoff date of 08Jan2021 (up to approx. 18 months)
Randomized Part: Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Health State Scores
The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of these dimensions, the participant self-assigned a score: from 1 (no problems) to 5 (extreme problems). The 5 digit health states obtained for each dimension was converted into a single mean index value based on the EQ-5D crosswalk value set for the UK using the time trade-off method. This index ranges from -0.594 (worst health) to 1.0 (best health). A positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits 1, 2, 3 and 5 were conducted every 6 weeks (for the first 12 months since start of treatment) and every 12 weeks (after 12 months since start of treatment) until disease progression
Baseline, every 3 weeks from Week 3 until end of treatment, every 6 or 12 weeks post-treatment until progression (post-treatment efficacy visits), 7 and 28 days post progression through final analysis cutoff date of 08Jan2021 (up to approx. 18 months)
Safety run-in Part: Maximum Plasma Concentration (Cmax) of Canakinumab
Venous whole blood samples were collected for pharmacokinetics characterization. Cmax of canakinumab was calculated from canakinumab plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Cycle 1 Day 1 at pre-dose and end of infusion and 24, 48, 168 and 336 hours (h) post-infusion. Each cycle is 21 days
Safety run-in Part: Time of Maximum Plasma Concentration (Tmax) of Canakinumab
Venous whole blood samples were collected for pharmacokinetics characterization. Tmax of canakinumab was calculated from canakinumab plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Actual recorded sampling times were considered for the calculations.
Cycle 1 Day 1 at pre-dose and end of infusion and 24, 48, 168 and 336 hours (h) post-infusion. Each cycle is 21 days
Safety run-in Part: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Canakinumab
Venous whole blood samples were collected for pharmacokinetics characterization. AUClast of canakinumab was calculated from canakinumab plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Cycle 1 Day 1 at pre-dose and end of infusion and 24, 48, 168 and 336 hours (h) post-infusion. Each cycle is 21 days
Safety run-in Part: Cmax of Docetaxel
Venous whole blood samples were collected for pharmacokinetics characterization. Cmax of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Cycle 1 Day 1 and Cycle 2 Day 1 at pre-infusion, end of infusion, and 2, 4, 6 and 8 hours post-dose. Each cycle is 21 days
Safety run-in Part: Tmax of Docetaxel
Venous whole blood samples were collected for pharmacokinetics characterization. Tmax of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Actual recorded sampling times were considered for the calculations.
Cycle 1 Day 1 and Cycle 2 Day 1 at pre-infusion, end of infusion, and 2, 4, 6 and 8 hours post-dose. Each cycle is 21 days
Safety run-in Part: AUClast of Docetaxel
Venous whole blood samples were collected for pharmacokinetics characterization. AUClast of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Cycle 1 Day 1 and Cycle 2 Day 1 at pre-infusion, end of infusion, and 2, 4, 6 and 8 hours post-dose. Each cycle is 21 days
Randomized Part: Pre-dose Plasma Trough Concentration (CTrough) of Canakinumab
Venous whole blood samples were collected for pharmacokinetics characterization. CTrough of canakinumab was calculated from canakinumab plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Pre-dose on Cycle 1 Day 1, Cycle 4 Day 1, Cycle 6 Day 1, Cycle 12 Day 1 and Cycle 18 Day 1. Each cycle is 21 days.
Randomized Part: Cmax of Docetaxel
Venous whole blood samples were collected for pharmacokinetics characterization. Cmax of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Cycle 1 Day 1 and Cycle 4 Day 1 at pre-infusion, end of infusion, and 2, 4 and 6 hours post-dose. Each cycle is 21 days
Randomized Part: Tmax of Docetaxel
Venous whole blood samples were collected for pharmacokinetics characterization. Tmax of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Actual recorded sampling times were considered for the calculations.
Cycle 1 Day 1 and Cycle 4 Day 1 at pre-infusion, end of infusion, and 2, 4 and 6 hours post-dose. Each cycle is 21 days
Randomized Part: AUClast of Docetaxel
Venous whole blood samples were collected for pharmacokinetics characterization. AUClast of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Cycle 1 Day 1 and Cycle 4 Day 1 at pre-infusion, end of infusion, and 2, 4 and 6 hours post-dose. Each cycle is 21 days
Randomized Part: Canakinumab Antidrug Antibodies (ADA) at Baseline
ADA prevalence at baseline was calculated as the percentage of participants who had an ADA positive result at baseline
Baseline
Randomized Part: Canakinumab ADA Incidence On-treatment
ADA incidence on-treatment was calculated as the percentage of participants who were treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
Pre-dose at Cycle 1 Day 1, Cycle 4 Day 1, Cycle 6 Day 1, Cycle 12 Day 1 , end of treatment, and 130 days after end of treatment through final analysis data cutoff date of 08-Jan-2021 (assessed up to 18 months). Each cycle is 21 days
Kansas City
Missouri
64111
United States
Montefiore Medical Center Albert Einstein College of Med
The Bronx
New York
10461
United States
University of Cincinnati Cancer Institute
Cincinnati
Ohio
45267
United States
MD Anderson
Houston
Texas
77030
United States
Huntsman Cancer Institute Univ of Utah .
Salt Lake City
Utah
84112 0550
United States
Novartis Investigative Site
Berazategui
Buenos Aires
B1884BBF
Argentina
Novartis Investigative Site
CABA
Buenos Aires
C1426ANZ
Argentina
Novartis Investigative Site
Mar del Plata
Buenos Aires
B7600FZN
Argentina
Novartis Investigative Site
La Rioja
5300
Argentina
Novartis Investigative Site
Santiago del Estero
4200
Argentina
Novartis Investigative Site
Greenslopes
Queensland
4120
Australia
Novartis Investigative Site
Shepparton
Victoria
3630
Australia
Novartis Investigative Site
Sint-Niklaas
Oost Vlaanderen
9100
Belgium
Novartis Investigative Site
Brussels
1200
Belgium
Novartis Investigative Site
Charleroi
6000
Belgium
Novartis Investigative Site
Ghent
9000
Belgium
Novartis Investigative Site
Roeselare
8800
Belgium
Novartis Investigative Site
Salvador
Estado de Bahia
40170-110
Brazil
Novartis Investigative Site
Porto Alegre
Rio Grande do Sul
90880-480
Brazil
Novartis Investigative Site
Itajaí
Santa Catarina
88301-229
Brazil
Novartis Investigative Site
Vancouver
British Columbia
V5Z 4E6
Canada
Novartis Investigative Site
Montreal
Quebec
H4A 3J1
Canada
Novartis Investigative Site
Santiago
7500006
Chile
Novartis Investigative Site
Chengdu
Sichuan
610041
China
Novartis Investigative Site
Shanghai
200433
China
Novartis Investigative Site
Brno-Bohunice
625 00
Czechia
Novartis Investigative Site
Ostrava Vitkovice
703 84
Czechia
Novartis Investigative Site
Herlev
DK 2730
Denmark
Novartis Investigative Site
Odense C
DK 5000
Denmark
Novartis Investigative Site
Le Mans
Cedex 09
72037
France
Novartis Investigative Site
Besançon
25030
France
Novartis Investigative Site
Bordeaux
33000
France
Novartis Investigative Site
Bron
69677
France
Novartis Investigative Site
Strasbourg
67091
France
Novartis Investigative Site
Berlin
13125
Germany
Novartis Investigative Site
Cologne
51109
Germany
Novartis Investigative Site
Dresden
01307
Germany
Novartis Investigative Site
Frankfurt
60488
Germany
Novartis Investigative Site
Gerlingen
70839
Germany
Novartis Investigative Site
Großhansdorf
22947
Germany
Novartis Investigative Site
Ulm
89081
Germany
Novartis Investigative Site
Heraklion Crete
Greece
711 10
Greece
Novartis Investigative Site
Thessaloniki
57001
Greece
Novartis Investigative Site
Törökbálint
Pest County
2045
Hungary
Novartis Investigative Site
Ramat Gan
52621
Israel
Novartis Investigative Site
Lucca
LU
55100
Italy
Novartis Investigative Site
Rozzano
MI
20089
Italy
Novartis Investigative Site
Aviano
PN
33081
Italy
Novartis Investigative Site
Nagoya
Aichi-ken
464 8681
Japan
Novartis Investigative Site
Himeji
Hyōgo
670-8520
Japan
Novartis Investigative Site
Yokohama
Kanagawa
241-8515
Japan
Novartis Investigative Site
Chuo Ku
Tokyo
104 0045
Japan
Novartis Investigative Site
Osaka
545-8586
Japan
Novartis Investigative Site
Amman
11941
Jordan
Novartis Investigative Site
El Achrafiyé
166830
Lebanon
Novartis Investigative Site
Amsterdam
1081 HV
Netherlands
Novartis Investigative Site
Groningen
9713 GZ
Netherlands
Novartis Investigative Site
Maastricht
6229 HX
Netherlands
Novartis Investigative Site
Gdansk
80 952
Poland
Novartis Investigative Site
Rzeszów
35-021
Poland
Novartis Investigative Site
Warsaw
02 781
Poland
Novartis Investigative Site
Pushkin Saint Petersburg
196603
Russia
Novartis Investigative Site
Saint Petersburg
197758
Russia
Novartis Investigative Site
Singapore
168583
Singapore
Novartis Investigative Site
Seoul
Seocho Gu
06591
South Korea
Novartis Investigative Site
Seoul
03722
South Korea
Novartis Investigative Site
Seoul
05505
South Korea
Novartis Investigative Site
Málaga
Andalusia
29010
Spain
Novartis Investigative Site
Badalona
Catalonia
08916
Spain
Novartis Investigative Site
A Coruña
Galicia
15006
Spain
Novartis Investigative Site
Valencia
Valencia
46014
Spain
Novartis Investigative Site
Madrid
28034
Spain
Novartis Investigative Site
Madrid
28040
Spain
Novartis Investigative Site
Madrid
28041
Spain
Novartis Investigative Site
Madrid
28222
Spain
Novartis Investigative Site
Tainan
70403
Taiwan
Novartis Investigative Site
Taipei
103616
Taiwan
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
FG002
Randomized Part: Placebo + Docetaxel
Participants were randomized to receive placebo subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
FG0008 subjects
FG001120 subjects
FG002117 subjects
Treated
FG0008 subjects
FG001120 subjects
FG002114 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
NOT COMPLETED
FG0008 subjects
FG001120 subjects
FG002117 subjects
Type
Comment
Reasons
Progressive disease
FG0003 subjects
FG00182 subjects
FG00285 subjects
Adverse Event
FG0003 subjects
FG00113 subjects
FG00210 subjects
Physician Decision
FG0001 subjects
FG00118 subjects
FG00214 subjects
Subject Decision
FG0000 subjects
FG0015 subjects
FG0025 subjects
Death
FG0001 subjects
FG0011 subjects
FG0021 subjects
Protocol Deviation
FG0000 subjects
FG0011 subjects
FG0021 subjects
Guardian Decision
FG0000 subjects
FG0010 subjects
FG0021 subjects
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Safety run-in Part: Canakinumab+Docetaxel
Participants were treated with full doses of docetaxel 75mg/m^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1).
BG001
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
BG002
Randomized Part: Placebo + Docetaxel
Participants were randomized to receive placebo subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0008
BG001120
BG002117
BG003245
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
BG00055.9± 4.19
BG00163.4± 9.13
BG00262.2± 10.05
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0002
BG00138
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
White
BG0008
BG00191
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: Percentage of Participants With Dose Limiting Toxicities (DLTs)
Percentage of participants with DLTs. A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 42 days of docetaxel and canakinumab treatment.
Participants in the safety run-in part to whom study treatment was assigned, who received at least one dose of any study treatment (including incomplete infusion) and met the minimum exposure criterion and have sufficient safety evaluations, or experienced a DLT during the first 42 days of dosing
Posted
Count of Participants
Participants
During the first 42 days of dosing
ID
Title
Description
OG000
Safety run-in Part: Canakinumab+Docetaxel
Participants were treated with full doses of docetaxel 75mg/m^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1).
Units
Counts
Participants
OG0007
Title
Denominators
Categories
Title
Measurements
OG0001
Primary
Randomized Part: Overall Survival (OS)
OS is defined as the time from randomization to date of death due to any cause. The OS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated for each treatment group. If a subject was not known to have died, then OS was censored at the latest date the subject was known to be alive (on or before the cut-off date).
Full Analysis Set (FAS) in randomized part: All participants to whom study treatment was assigned by randomization.
Posted
Median
95% Confidence Interval
Months
From randomization until death or final analysis data cutoff date (08-Jan-2021) whichever comes first (up to approximately (approx.) 18 months)
ID
Title
Description
OG000
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
OG001
Randomized Part: Placebo + Docetaxel
Participants were randomized to receive placebo subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
Units
Counts
Participants
Secondary
Overall Response Rate (ORR)
ORR is defined as the percentage of participants with confirmed best overall response of complete response (CR) or partial response (PR), as per investigator's assessment by RECIST 1.1. The 95% confidence intervals (CIs) were computed using Clopper and Pearson method.
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.
FAS in Safety run-in part: all participants to whom study treatment was assigned and who received at least one dose of any study treatment (including incomplete infusion) FAS in Randomized part: all participants to whom study treatment was assigned by randomization
Posted
Number
95% Confidence Interval
Percentage of participants
Through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 10 months for the safety run-in part and 18 months for the randomized part)
ID
Title
Description
OG000
Safety run-in Part: Canakinumab+Docetaxel
Participants were treated with full doses of docetaxel 75mg/m^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1).
OG001
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
Secondary
Duration of Response (DOR)
DOR is defined as the time from first documented response of CR or PR to date of first documented progression or death, by investigator's assessment according to RECIST 1.1 criteria. The DOR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated for each treatment group.
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.
FAS in Safety run-in part: all participants to whom study treatment was assigned and who received at least one dose of any study treatment (including incomplete infusion) for whom best overall response is CR or PR FAS in Randomized part: all participants to whom study treatment was assigned by randomization for whom best overall response is CR or PR
Posted
Median
95% Confidence Interval
Months
From first documented response of CR or PR to date of first documented progression, death or final analysis data cutoff date (08-Jan-2021) whichever comes first (up to approx. 10 months for the safety run-in and 18 months for the randomized)
ID
Title
Description
OG000
Safety run-in Part: Canakinumab+Docetaxel
Participants were treated with full doses of docetaxel 75mg/m^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1).
OG001
Randomized Part: Canakinumab + Docetaxel
Secondary
Disease Control Rate (DCR)
DCR is defined as the percentage of participants with CR or PR or with stable disease (SD) as per investigator assessment according to RECIST 1.1 criteria. The 95% CIs were computed using Clopper and Pearson method.
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.
SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
FAS in Safety run-in part: all participants to whom study treatment was assigned and who received at least one dose of any study treatment (including incomplete infusion) FAS in Randomized part: all participants to whom study treatment was assigned by randomization
Posted
Number
95% Confidence Interval
Percentage of participants
Through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 10 months for the safety run-in part and 18 months for the randomized part)
ID
Title
Description
OG000
Safety run-in Part: Canakinumab+Docetaxel
Participants were treated with full doses of docetaxel 75mg/m^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1).
OG001
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
Secondary
Randomized Part: Progression-Free Survival (PFS)
PFS is defined as the time from randomization to the date of the first documented radiological progression by investigator assessment according to RECIST 1.1 response criteria or death due to any cause.
The PFS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated for each treatment group. If a participant did not have disease progression or die at the analysis cut-off date, PFS was censored at the date of last adequate tumor assessment.
FAS in Randomized part: All participants to whom study treatment was assigned by randomization
Posted
Median
95% Confidence Interval
Months
From randomization until disease progression, death or final analysis data cutoff date (08-Jan-2021) whichever comes first (assessed up to approx. 18 months)
ID
Title
Description
OG000
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
OG001
Randomized Part: Placebo + Docetaxel
Participants were randomized to receive placebo subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
Secondary
Randomized Part: Time to Response (TTR)
TTR is defined as the time from the date of randomization to the date of first documented response of either CR or PR, by investigator's assessment according to RECIST 1.1 criteria. The TTR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated for each treatment group. Subjects without a confirmed CR or PR at the time of the analysis cut-off date were censored at the study-maximum follow-up time for subjects with a PFS event (i.e., disease progression or death due to any cause), or at the date of the last adequate tumor assessment for subjects without a PFS event.
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.
FAS in Randomized part: All participants to whom study treatment was assigned by randomization
Posted
Median
95% Confidence Interval
Months
From randomization until first documented response or final analysis data cutoff date (08-Jan-2021) whichever comes first (up to approx. 18 months)
ID
Title
Description
OG000
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
OG001
Randomized Part: Placebo + Docetaxel
Secondary
Randomized Part: Time to Definitive 10-point Deterioration (TTD) Symptom Scores of Chest Pain, Cough and Dyspnea Per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) Lung Cancer (LC13) Questionnaire
The EORTC QLQ-LC13 comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, dyspnea, and chest pain) and treatment-related symptoms from conventional chemotherapy and radiotherapy (ie. hair loss, neuropathy, sore mouth, and dysphagia). Scores for each scale and single-item range from 0 to 100, with higher scores indicating higher level of symptoms. TTD for chest pain, cough and dyspnea is defined as the time from randomization to the date of event, which is defined as at least 10 points absolute worsening from baseline of the corresponding scale score, with no later change below this threshold ie.<10 points was observed or if this worsening was observed at the last assessment for the subject, or death due to any cause (whichever occurs earlier). If a subject did not have an event, TTD was censored at the last adequate assessment.
FAS in Randomized part: All participants to whom study treatment was assigned by randomization
Posted
Median
95% Confidence Interval
Months
From baseline through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 18 months)
ID
Title
Description
OG000
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
OG001
Secondary
Randomized Part: Time to Definitive 10-point Deterioration in Global Health Status (GHS)/Quality of Life (QoL), Shortness of Breath and Pain Per EORTC QLQ-C30 Questionnaire
The EORTC QLQ-C30 includes 5 functional scales (physical,role,cognitive,emotional and social), 3 symptom scales (fatigue,pain and nausea/vomiting), a GHS/QoL scale, and 6 single items (constipation,diarrhea,insomnia,shortness of breath,appetite loss and financial difficulties). For each scale and single-item, scores range between 0 and 100. A high score for functional scales/ GHS/QoL represents better functioning or QoL, a high score for symptom scales/single items represents significant symptomatology. TTD in GHS/QoL, shortness of breath and pain is defined as the time from randomization to the date of event, defined as at least 10 points absolute worsening from baseline of the corresponding scale score, with no later change below this threshold i.e.<10 points was observed or if this worsening was observed at the last assessment for the subject, or death due to any cause (whichever occurs earlier). If a subject did not have an event, TTD was censored at the last adequate assessment.
FAS in Randomized part: All participants to whom study treatment was assigned by randomization
Posted
Median
95% Confidence Interval
Months
From baseline through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 18 months)
ID
Title
Description
OG000
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
Secondary
Randomized Part: Change From Baseline in GHS/QoL, Shortness of Breath and Pain Scores as Per the EORTC QLQ C30 Questionnaire
The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/QoL scale, and 6 single items (constipation, diarrhea, insomnia, dyspnoea, appetite loss and financial difficulties). For each scale and item, scores range 0-100. A high score for functional scales/QoL represents better functioning/QoL; a high score for symptom scales and items represents significant symptomatology. Changes from baseline in QoL, shortness of breath and pain scores are presented. For QoL, a negative change from baseline indicates improvement; for shortness of breath and pain a positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits 1, 2, 3 and 5 were conducted every 6 weeks (for the first 12 months since start of treatment) and every 12 weeks (after 12 months since start of treatment) until disease progression
FAS in Randomized part: All participants to whom study treatment was assigned by randomization. Number analyzed represents participants with data available at the specified data points
Posted
Mean
Standard Deviation
Score on a scale
Baseline, every 3 weeks from Week 3 until end of treatment, every 6 or 12 weeks post-treatment until progression (post-treatment efficacy visits), 7 and 28 days post progression through final analysis cutoff date of 08Jan2021 (up to approx. 18 months)
ID
Title
Description
OG000
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
Secondary
Randomized Part: Change From Baseline in Chest Pain, Cough and Dyspnea Scores as Per the EORTC-QLQ LC13 Questionnaire
The EORTC QLQ-LC13 is a 13-item questionnaire. It comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, dyspnea, and chest pain) and treatment-related symptoms from conventional chemotherapy and radiotherapy (ie, hair loss, neuropathy, sore mouth, and dysphagia). Scores for each scale and single-item range from 0 to 100, with higher scores indicating higher ("worse") level of symptoms. Changes from baseline in chest pain, cough and dyspnea scores are presented. A positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits 1, 2, 3 and 5 were conducted every 6 weeks (for the first 12 months since start of treatment) and every 12 weeks (after 12 months since start of treatment) until disease progression
FAS in Randomized part: All participants to whom study treatment was assigned by randomization. Number analyzed represents participants with data available at the specified data points
Posted
Mean
Standard Deviation
Score on a scale
Baseline, every 3 weeks from Week 3 until end of treatment, every 6 or 12 weeks post-treatment until progression (post-treatment efficacy visits), 7 and 28 days post progression through final analysis cutoff date of 08Jan2021 (up to approx. 18 months)
ID
Title
Description
OG000
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
Secondary
Randomized Part: Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Health State Scores
The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of these dimensions, the participant self-assigned a score: from 1 (no problems) to 5 (extreme problems). The 5 digit health states obtained for each dimension was converted into a single mean index value based on the EQ-5D crosswalk value set for the UK using the time trade-off method. This index ranges from -0.594 (worst health) to 1.0 (best health). A positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits 1, 2, 3 and 5 were conducted every 6 weeks (for the first 12 months since start of treatment) and every 12 weeks (after 12 months since start of treatment) until disease progression
FAS in Randomized part: All participants to whom study treatment was assigned by randomization. Number analyzed represents participants with data available at the specified data points
Posted
Mean
Standard Deviation
Score on a scale
Baseline, every 3 weeks from Week 3 until end of treatment, every 6 or 12 weeks post-treatment until progression (post-treatment efficacy visits), 7 and 28 days post progression through final analysis cutoff date of 08Jan2021 (up to approx. 18 months)
ID
Title
Description
OG000
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
Secondary
Safety run-in Part: Maximum Plasma Concentration (Cmax) of Canakinumab
Venous whole blood samples were collected for pharmacokinetics characterization. Cmax of canakinumab was calculated from canakinumab plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Canakinumab pharmacokinetic analysis set (PAS) in safety run-in part: all subjects who received at least one dose of canakinumab in the safety run-in part and have at least one evaluable canakinumab pharmacokinetic (PK) concentration. Only participants with an evaluable PK sample collected at each timepoint were included in this analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
microgram/milliliter (ug/mL)
Cycle 1 Day 1 at pre-dose and end of infusion and 24, 48, 168 and 336 hours (h) post-infusion. Each cycle is 21 days
ID
Title
Description
OG000
Safety run-in Part: Canakinumab+Docetaxel
Participants were treated with full doses of docetaxel 75mg/m^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1).
Units
Counts
Participants
OG000
Secondary
Safety run-in Part: Time of Maximum Plasma Concentration (Tmax) of Canakinumab
Venous whole blood samples were collected for pharmacokinetics characterization. Tmax of canakinumab was calculated from canakinumab plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Actual recorded sampling times were considered for the calculations.
Canakinumab PAS in safety run-in part: all subjects who received at least one dose of canakinumab in the safety run-in part and have at least one evaluable canakinumab PK concentration. Only participants with an evaluable PK sample collected at each timepoint were included in this analysis
Posted
Median
Full Range
Hours (h)
Cycle 1 Day 1 at pre-dose and end of infusion and 24, 48, 168 and 336 hours (h) post-infusion. Each cycle is 21 days
ID
Title
Description
OG000
Safety run-in Part: Canakinumab+Docetaxel
Participants were treated with full doses of docetaxel 75mg/m^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1).
Units
Counts
Participants
OG000
Secondary
Safety run-in Part: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Canakinumab
Venous whole blood samples were collected for pharmacokinetics characterization. AUClast of canakinumab was calculated from canakinumab plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Canakinumab PAS in safety run-in part: all subjects who received at least one dose of canakinumab in the safety run-in part and have at least one evaluable canakinumab PK concentration. Only participants with an evaluable PK sample collected at each timepoint were included in this analysis
Posted
Geometric Mean
Geometric Coefficient of Variation
hour*microgram/mililiter (hr*ug/mL)
Cycle 1 Day 1 at pre-dose and end of infusion and 24, 48, 168 and 336 hours (h) post-infusion. Each cycle is 21 days
ID
Title
Description
OG000
Safety run-in Part: Canakinumab+Docetaxel
Participants were treated with full doses of docetaxel 75mg/m^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1).
Units
Counts
Participants
OG000
Secondary
Safety run-in Part: Cmax of Docetaxel
Venous whole blood samples were collected for pharmacokinetics characterization. Cmax of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Docetaxel PAS in safety run-in part: all subjects who received at least one dose of canakinumab in the safety run-in part and have at least one evaluable docetaxel PK concentration. Number analyzed represents participants evaluable at specified time points
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram/miliLiter (ng/mL)
Cycle 1 Day 1 and Cycle 2 Day 1 at pre-infusion, end of infusion, and 2, 4, 6 and 8 hours post-dose. Each cycle is 21 days
ID
Title
Description
OG000
Safety run-in Part: Canakinumab+Docetaxel
Participants were treated with full doses of docetaxel 75mg/m^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1).
Units
Counts
Participants
OG000
Secondary
Safety run-in Part: Tmax of Docetaxel
Venous whole blood samples were collected for pharmacokinetics characterization. Tmax of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Actual recorded sampling times were considered for the calculations.
Docetaxel PAS in safety run-in part: all subjects who received at least one dose of canakinumab in the safety run-in part and have at least one evaluable docetaxel PK concentration. Number analyzed represents participants evaluable at specified time points
Posted
Median
Full Range
Hour (hr)
Cycle 1 Day 1 and Cycle 2 Day 1 at pre-infusion, end of infusion, and 2, 4, 6 and 8 hours post-dose. Each cycle is 21 days
ID
Title
Description
OG000
Safety run-in Part: Canakinumab+Docetaxel
Participants were treated with full doses of docetaxel 75mg/m^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1).
Units
Counts
Participants
OG000
Secondary
Safety run-in Part: AUClast of Docetaxel
Venous whole blood samples were collected for pharmacokinetics characterization. AUClast of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Docetaxel PAS in safety run-in part: all subjects who received at least one dose of canakinumab in the safety run-in part and have at least one evaluable docetaxel PK concentration. Number analyzed represents participants evaluable at specified time points
Posted
Geometric Mean
Geometric Coefficient of Variation
Hour *nanogram/miliLiter (hr*ng/mL)
Cycle 1 Day 1 and Cycle 2 Day 1 at pre-infusion, end of infusion, and 2, 4, 6 and 8 hours post-dose. Each cycle is 21 days
ID
Title
Description
OG000
Safety run-in Part: Canakinumab+Docetaxel
Participants were treated with full doses of docetaxel 75mg/m^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1).
Units
Counts
Participants
OG000
Secondary
Randomized Part: Pre-dose Plasma Trough Concentration (CTrough) of Canakinumab
Venous whole blood samples were collected for pharmacokinetics characterization. CTrough of canakinumab was calculated from canakinumab plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Canakinumab PAS in randomized part: all subjects who received at least one dose of canakinumab in the randomized part and have at least one evaluable canakinumab pharmacokinetic (PK) concentration. Number analyzed represents participants evaluable at specified time points.
Posted
Geometric Mean
Geometric Coefficient of Variation
microgram/miliLiter (ug/mL)
Pre-dose on Cycle 1 Day 1, Cycle 4 Day 1, Cycle 6 Day 1, Cycle 12 Day 1 and Cycle 18 Day 1. Each cycle is 21 days.
ID
Title
Description
OG000
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
Units
Counts
Participants
OG000
Secondary
Randomized Part: Cmax of Docetaxel
Venous whole blood samples were collected for pharmacokinetics characterization. Cmax of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Docetaxel PAS in randomized part: all subjects who received at least one dose of canakinumab in the randomized part and have at least one evaluable docetaxel PK concentration. Number analyzed represents participants evaluable at specified time points
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram/miliLiter (ng/mL)
Cycle 1 Day 1 and Cycle 4 Day 1 at pre-infusion, end of infusion, and 2, 4 and 6 hours post-dose. Each cycle is 21 days
ID
Title
Description
OG000
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
OG001
Randomized Part: Placebo + Docetaxel
Participants were randomized to receive placebo subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
Units
Counts
Secondary
Randomized Part: Tmax of Docetaxel
Venous whole blood samples were collected for pharmacokinetics characterization. Tmax of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Actual recorded sampling times were considered for the calculations.
Docetaxel PAS in randomized part: all subjects who received at least one dose of canakinumab in the randomized part and have at least one evaluable docetaxel PK concentration. Number analyzed represents participants evaluable at specified time points
Posted
Median
Full Range
Hour
Cycle 1 Day 1 and Cycle 4 Day 1 at pre-infusion, end of infusion, and 2, 4 and 6 hours post-dose. Each cycle is 21 days
ID
Title
Description
OG000
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
OG001
Randomized Part: Placebo + Docetaxel
Participants were randomized to receive placebo subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
Units
Counts
Secondary
Randomized Part: AUClast of Docetaxel
Venous whole blood samples were collected for pharmacokinetics characterization. AUClast of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Docetaxel PAS in randomized part: all subjects who received at least one dose of canakinumab in the randomized part and have at least one evaluable docetaxel PK concentration. Number analyzed represents participants evaluable at specified time points
Posted
Geometric Mean
Geometric Coefficient of Variation
hour*nanogram/miliLiter (h*ng/mL)
Cycle 1 Day 1 and Cycle 4 Day 1 at pre-infusion, end of infusion, and 2, 4 and 6 hours post-dose. Each cycle is 21 days
ID
Title
Description
OG000
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
OG001
Randomized Part: Placebo + Docetaxel
Participants were randomized to receive placebo subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
Units
Counts
Secondary
Randomized Part: Canakinumab Antidrug Antibodies (ADA) at Baseline
ADA prevalence at baseline was calculated as the percentage of participants who had an ADA positive result at baseline
All participants randomized to canakinumab+docetaxel arm
Posted
Count of Participants
Participants
Baseline
ID
Title
Description
OG000
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
Units
Counts
Participants
OG000120
Secondary
Randomized Part: Canakinumab ADA Incidence On-treatment
ADA incidence on-treatment was calculated as the percentage of participants who were treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
All participants randomized to canakinumab+docetaxel arm
Posted
Count of Participants
Participants
Pre-dose at Cycle 1 Day 1, Cycle 4 Day 1, Cycle 6 Day 1, Cycle 12 Day 1 , end of treatment, and 130 days after end of treatment through final analysis data cutoff date of 08-Jan-2021 (assessed up to 18 months). Each cycle is 21 days
ID
Title
Description
OG000
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
Units
Counts
Participants
OG000
Post-Hoc
All Collected Deaths
Pre-treatment deaths were collected from screening to the first day of treatment, for a maximum duration of 28 days.
On-treatment deaths due to any cause were collected from first dose of study treatment to 130 days after the last dose of study treatment.
Post-treatment survival follow-up deaths were collected from day 131 after last dose of study treatment to end of study.
All deaths refer to the sum of pre-treatment, on-treatment and post-treatment deaths.
Safety run-in part: FAS including all subjects to whom study treatment was assigned.
Randomized part: FAS including all participants to whom study treatment was assigned by randomization
Posted
Count of Participants
Participants
Pre-treatment: up to 28 days before Day 1;On-treatment: up to approximately 10 months (safety run-in) or 25 months (randomized); post-treatment survival follow-up deaths: Up to approximately 16 months (safety run in) or 25 months (randomized)
ID
Title
Description
OG000
Safety run-in Part: Canakinumab+Docetaxel
Participants were treated with full doses of docetaxel 75mg/m^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1).
OG001
Randomized Part: Canakinumab + Docetaxel
Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 on Day 1 of each 21-Day cycle
Time Frame
Treatment-emergent Adverse events (AEs) were collected from first administration of study treatment to 130 days after date of last administration, up to approximately 10 months (safety run-in) or 25 months (randomized). Deaths were collected from day of subject's informed consent until end of study, up to approximately 16 months (safety run in) or 25 months (randomized)
Description
Treatment-emergent AEs refer to any signs or symptoms observed during the study treatment and up to 130 days after treatment, considering the Safety Set. This set includes all subjects who were assigned study treatment and received at least one dose, including incomplete infusions.
All-Cause Mortality analysis encompasses the Full Analysis Set, including all subjects who were assigned study treatment
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
All Participants (Pre-treatment)
Deaths were collected in the pre-treatment period (from day of patient's informed consent to the day before first administration of study treatment )
Deaths collected in the post- treatment follow-up period (starting from day 131 post- treatment). No AEs were collected during this period
38
77
0
0
0
0
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG0031 affected120 at risk
EG0040 at risk
EG0050 affected114 at risk
EG0060 at risk
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Cardiac tamponade
Cardiac disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Cardio-respiratory arrest
Cardiac disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Pericardial effusion
Cardiac disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Hypopituitarism
Endocrine disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Colitis ulcerative
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Ileus
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Lower gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Small intestine ulcer
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Asthenia
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Chest pain
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Disease progression
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Fatigue
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Generalised oedema
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Malaise
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Mucosal inflammation
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Oedema peripheral
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Pyrexia
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Abdominal sepsis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Bacteraemia
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Bacterial infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
COVID-19
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
COVID-19 pneumonia
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Clostridium difficile colitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Device related infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Diverticulitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Erysipelas
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Escherichia sepsis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Escherichia urinary tract infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Febrile infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Gastroenteritis viral
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Infectious pleural effusion
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Influenza
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Neutropenic sepsis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0012 affected8 at risk
EG0020 at risk
EG003
Pneumonia pneumococcal
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Pneumonia pseudomonal
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Post procedural sepsis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Pulmonary sepsis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Sepsis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Septic shock
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Spinal cord infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Urosepsis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Vulvovaginitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Femur fracture
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Hip fracture
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Lumbar vertebral fracture
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Procedural pneumothorax
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
White blood cell count decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Diabetic ketoacidosis
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Fistula
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Cancer pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Cerebrovascular accident
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Ischaemic stroke
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Monoplegia
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Syncope
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Balanoposthitis
Reproductive system and breast disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Asthma
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Interstitial lung disease
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Pneumothorax
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Aneurysm
Vascular disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Haematoma
Vascular disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Hypotension
Vascular disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Superior vena cava syndrome
Vascular disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Thrombosis
Vascular disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG00332 affected120 at risk
EG0040 at risk
EG00533 affected114 at risk
EG0060 at risk
Leukopenia
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0012 affected8 at risk
EG0020 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Cushingoid
Endocrine disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0013 affected8 at risk
EG0020 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Odynophagia
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0012 affected8 at risk
EG0020 at risk
EG003
Asthenia
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0012 affected8 at risk
EG0020 at risk
EG003
Chest pain
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Fatigue
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Influenza like illness
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Malaise
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Mucosal inflammation
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Oedema
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Oedema peripheral
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0013 affected8 at risk
EG0020 at risk
EG003
Pyrexia
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Folliculitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0012 affected8 at risk
EG0020 at risk
EG003
Haemoglobin decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
SARS-CoV-2 test negative
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Weight decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
White blood cell count decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0012 affected8 at risk
EG0020 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Steroid diabetes
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Tumour pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Headache
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Neuropathy peripheral
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Taste disorder
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0012 affected8 at risk
EG0020 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0012 affected8 at risk
EG0020 at risk
EG003
Dyspnoea exertional
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Productive cough
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Nail disorder
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Night sweats
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Psoriasis
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0010 affected8 at risk
EG0020 at risk
EG003
Hypotension
Vascular disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 at risk
EG003
Phlebitis
Vascular disorders
MedDRA (23.1)
Systematic Assessment
EG0000 at risk
EG0011 affected8 at risk
EG0020 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. However, 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.