Study of Dose Confirmation and Safety of Crizanlizumab in... | NCT03474965 | Trialant
NCT03474965
Sponsor
Novartis Pharmaceuticals
Status
Completed
Last Update Posted
Oct 16, 2025Actual
Enrollment
117Actual
Phase
Phase 2
Conditions
Sickle Cell Disease (SCD)
Interventions
Crizanlizumab
Countries
United States
Belgium
Brazil
Canada
Colombia
France
Germany
India
Italy
Lebanon
Oman
Spain
Turkey (Türkiye)
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT03474965
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CSEG101B2201
Secondary IDs
ID
Type
Description
Link
2017-001747-12
EudraCT Number
Brief Title
Study of Dose Confirmation and Safety of Crizanlizumab in Pediatric Sickle Cell Disease Patients
Official Title
A Phase 2,Multicenter,Open-Label Study to Assess Appropriate Dosing and to Evaluate Safety of Crizanlizumab,With or Without Hydroxyurea/Hydroxycarbamide,in Sequential,Descending Age Groups of Pediatric Sickle Cell Disease Patients With Vaso-Occlusive Crisis
Acronym
Not provided
Organization
NovartisINDUSTRY
Status Module
Record Verification Date
Oct 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
Not provided
Start Date
Oct 1, 2018Actual
Primary Completion Date
Nov 6, 2024Actual
Completion Date
Nov 6, 2024Actual
First Submitted Date
Mar 16, 2018
First Submission Date that Met QC Criteria
Mar 16, 2018
First Posted Date
Mar 23, 2018Actual
Results Waived
Not provided
Results First Submitted Date
May 1, 2025
Results First Submitted that Met QC Criteria
Jul 1, 2025
Results First Posted Date
Jul 20, 2025Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Oct 8, 2025
Last Update Posted Date
Oct 16, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Novartis PharmaceuticalsINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The purpose of this study was to confirm and to establish appropriate dosing and to evaluate the safety in pediatric participants ages 2 to <18 years with a history of Vaso-Occlusive Crisis (VOC) with or without Hydroxyurea/Hydroxycarbamide (HU/HC), receiving crizanlizumab for 2 years. The efficacy and safety of crizanlizumab was previously demonstrated in adults with sickle cell disease. The approach was to extrapolate from the pharmacokinetics (PK)/pharmacodynamics (PD) already established in the adult population. The study was designed as a Phase II, multicenter, open-label study.
Detailed Description
This was an open-label, single-arm study of crizanlizumab in sickle-cell disease (SCD) pediatric participants.
This study consisted of 2 parts, Part A and Part B. In Part A, the dose for 3 age groups (see groups below), was first confirmed on the basis of single and multiple dose (steady state) PK data and key safety data from an initial subgroup of participants. In Part B, safety and efficacy were collected from additional participants from 6 to <18 years (Groups 1 and 2, only).
At least 100 participants were planned to be enrolled in the trial in total, split in 3 age groups:
Group 1 (age 12 to <18 years): at least 26 participants (≥8 in Part A and ≥18 in Part B),
Group 2 (age 6 to <12 years): at least 26 participants (≥8 in Part A and ≥18 in Part B),
Group 3 (age 2 to <6 years): at least 8 participants (≥8 Part A). Crizanlizumab was administered every 4 weeks with a loading dose 2 weeks after the first dosing (i.e., by i.v. infusion) on Week 1 Day 1, Week 3 Day 1, and then day 1 of every fourth week) for up to 2 years. The initial dose of crizanlizumab was 5 mg/kg dose for Group 1 and Group 2 Part A. It was later adjusted to 8.5 mg/kg for Group 2 and 3 based on final dose confirmation from emerging PK data analysis and safety considerations determined in Part A of the study.
Conditions Module
Conditions
Sickle Cell Disease (SCD)
Keywords
SEG101
Sickle cell disease
SCD
crizanlizumab
pediatric
pharmacokinetic
P-selectin
Covid-19
Coronavirus disease 2019
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
117Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Crizanlizumab
Experimental
SEG101 (crizanlizumab) 5 mg/kg or 8 mg/kg i.v. administered on Week 1 Day 1, Week3 Day 1 and Day 1 of every 4-week cycle for up to 2 years. The initial dose of crizanlizumab was 5 mg/kg dose for Group 1 and Group 2 Part A. It was later adjusted to 8.5 mg/kg for Group 2 and 3 based on final dose confirmation from emerging PK data analysis and safety considerations determined in Part A of the study.
Drug: Crizanlizumab
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Crizanlizumab
Drug
Crizanlizumab (SEG101) is a concentrate for solution for infusion, i.v. use. Supplied in single use 10 mL vials at a concentration of 10 mg/mL. One vial contains 100 mg of crizanlizumab.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Pharmacokinetics (PK): AUCd15 of Crizanlizumab After First Dose - Part A
The area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) following the first dose. AUCd15 was calculated based on serum concentrations of crizanlizumab.
Day 1 to Day 15
Pharmacokinetics (PK) - AUCtau for Serum Crizanlizumab After Multiple Doses - Part A - Steady State
The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1).
Week 15 - Steady state
Pharmacokinetics (PK) - Cmax for Crizanlizumab After First Dose and Multiple Doses - Part A - Steady State
The maximum (peak) observed, serum, drug concentration after single or multiple dose administration (mass x volume-1)
Week 1 (after first dose) and Week 15 (steady state)
Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab After First Dose - Part A - AUCd15
The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) following the first dose. AUCd15 was calculated based on P-selectin inhibition curves.
Day 1 to Day 15
Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab - Part A - AUCtau After Multiple Dose - Steady State
The AUC of %inhibition calculated to the end of a dosing interval (tau) after multiple dose. AUCtau was calculated based on P-selectin inhibition curves.
Week 15 - Steady state
Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability
Secondary Outcomes
Measure
Description
Time Frame
Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
The baseline annualized rate of VOC was defined as the number of VOCs leading to healthcare visit occurring within the last 12 months prior to screening until first dose.
This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B)
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Male or female patients ages 2 to <18 years
Confirmed diagnosis of SCD (any genotype including HbSS, HbSC, HbSβ0-thalassemia, HbSβ+-thalassemia patients, and others) by hemoglobin electrophoresis or/and high-performance liquid chromatography (HPLC) [performed locally]. Confirmation of diagnosis by two accepted methods is recommended.
Experienced at least 1 VOC within the preceding 12 months prior to screening, as determined by medical history. Prior VOC must have resolved at least 7 days prior to the first dose in the study and must include all the following: a.the occurrence of appropriate symptoms (see VOC definition in Section 7.2.1.1), b.either a visit to a medical facility or healthcare professional, c.receipt of oral/parenteral opioid or parenteral NSAIDs
If receiving HU/HC, L-glutamine or erythropoietin stimulating agent, must have been receiving the drug consistently for at least 6 months prior to screening and plan to continue taking it at the same dose and schedule during the trial. Patients who have not been receiving such drugs must have been off them for at least 6 months prior to screening. . Dose alterations of HU/HC, L-glutamine or erythropoietin stimulating agent during Part A are not allowed, and if this occurs, the participant will enter directly to Part B.
Received standard age-appropriate care for SCD, including penicillin prophylaxis, pneumococcal immunization, and parental education.
Performance status: Karnofsky ≥ 50% for patients >10 years of age, and Lansky ≥ 50 for patients ≤ 10 years of age.
Patient must meet the following laboratory values prior to Week 1 Day 1: Absolute Neutrophil Count ≥1.0 x 109/L , Platelets ≥75 x 109/L, Hemoglobin (Hgb) > 5.5 g/dL
Patient must have adequate renal and hepatic function as defined:Estimated Glomerular filtration rate (eGFR) ≥ 75 mL/min/1.73 m2 using Schwartz formula, Direct (conjugated) bilirubin ≤ 2.0 x ULN, Alanine transaminase (ALT) ≤ 3.0 x ULN,
Transcranial Doppler (TCD) for patients aged 2 to < 16 years at time of screening, with HbSS, HbSβ0-thalassemia, and HbSD disease indicating low risk for stroke (per investigator). Please refer to Section 7.2.2.6 for details
Written informed consent/assent, according to local guidelines, signed by the patient and / or by the parents or legal guardian prior to any study related screening procedures are performed.
Female of non-childbearing potential or with negative serum pregnancy test on Screening and a negative urine pregnancy test (dipstick) prior to dosing on Day 1.
Exclusion Criteria:
History of stem cell transplant.
Received any blood products within 30 days prior to Week 1 Day 1 dosing.
Plan to participate in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes) or undergo exchange transfusions/plasmapheresis during the study. Patients requiring episodic transfusion (simple or exchange) in response to worsened anemia or VOC are permitted.
Patients with bleeding disorders
6.Contraindication or hypersensitivity to any drug from similar class as study drug or to any excipients of the study drug formulation.
7.History of severe hypersensitivity reaction to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction 8.Received a monoclonal antibody or immunoglobulin-based therapy within 6 months of Screening, or has documented immunogenicity to a prior monoclonal antibody.
9.Received active treatment on another investigational trial within 30 days (or 5 half -lives of that agent, whichever is greater) prior to Screening or plans to participate in another investigational drug trial.
10.Pregnant females or females who have given birth within the past 90 days or who are breastfeeding.
11. Any documented history of a clinical stroke or intracranial hemorrhage, or an uninvestigated neurologic finding within the past 12 months. Silent infarcts (only present on imaging) are not excluding patients from study participation 12.Any abnormal TCD within the past 12 months. 13.Use of therapeutic anticoagulation (prophylactic doses permitted) or antiplatelet therapy (other than aspirin) within the 10 days prior to Week 1 Day 1 dosing.
14.Hospitalized within 7 days prior to Week 1 Day 1 dosing. 15.Planning to undergo a major surgical procedure during the duration of the study.
16.Planning to initiate or terminate HU/HC or L-glutamine while on study (except if needed to terminate for safety reasons).
17.Patient with active human immunodeficiency virus (HIV) infection (detectable viral load).
18.Patients with known active Hepatitis B infection. 19.Patients with known Hepatitis C history. 20.Significant active infection or immune deficiency (including chronic use of immunosuppressive drugs) in the opinion of the investigator.
21.Malignant disease. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; any completely resected carcinoma in situ.
22.Has a serious mental or physical illness, which, in the opinion of the Investigator would compromise participation in the study.
23.Any condition which, in the opinion of the investigator, is likely to interfere with the successful collection of the measurements required for the study 24.Resting QTcF ≥450 msec at pretreatment (baseline) for patients under 12 years of age and ≥450 msec for males and ≥460 msec for female patients 12 years and older.
25.Cardiac or cardiac repolarization abnormality, including any of the following: a. History of myocardial infarction (MI), uncontrolled congestive heart failure, unstable angina, or coronary bypass graft (CABG) within 6 months prior to starting study treatment, b. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (bifascicular block, Mobitz Type II, and third degree AV block), c. Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome ( Risk factors for Torsade de Pointes (TdP), including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/ symptomatic bradycardia, Inability to determine the QTcF).
26. Sexually active females who are unwilling to comply with reliable method of birth control until 15 weeks following last dose of study drug.
28.Not able to understand and to comply with study instructions and requirements.
29.Patients who are an employee of the sponsor or investigator or otherwise dependent on them.
30.Patients who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
31.Patients who received prior crizanlizumab treatment and/or other selectin targeting agents are not allowed 32.Patients having taken voxelotor less than 30 days prior to Screening, or planning to take voxelotor while on study are not allowed.
Del Pozo Martin Y. 2021 ASH annual meeting. Lancet Haematol. 2022 Feb;9(2):e92-e93. doi: 10.1016/S2352-3026(21)00384-7. Epub 2021 Dec 16. No abstract available.
See Also Links
Label
URL
A Plain Language Trial Summary is available on www.novctrd.com
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent 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.
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject
Adverse events are reported from the first dose of study treatment until end of study treatment Week 103 plus 105 days post-treatment follow-up, up to a maximum timeframe of approximately 2 years and 3.25 months.
Baseline, Year 1 and Year 2
Annualized Rate Vaso Occlusive Crisis (VOC) Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With the Patient)
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B)
Up to Year 2
Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Uncomplicated Pain Crisis
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B)
Uncomplicated pain crisis is defined as an acute episode of pain with no known cause for pain other than a vaso-occlusive event; and requiring treatment with a parenteral or oral opioids or other parenteral analgesic; but is NOT classified as an acute chest syndrome, hepatic sequestration, splenic sequestration or priapism. The end of an uncomplicated pain crisis will be considered the resolution of acute pain, such that residual pain (or absence of any pain) is considered to be chronic, and the current pain medication regimen is considered to be for this chronic pain.
Up to Year 2
Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Acute Chest Syndrome
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B)
Acute Chest Syndrome (ACS) is defined on the basis of the finding of a new pulmonary infiltrate involving at least one complete lung segment that was consistent with alveolar consolidation, but excluding atelectasis (as indicated by chest X-ray). At least one of the following additional signs or symptoms needs to be present as well: chest pain, a temperature of more than 38.5°C, tachypnea, wheezing or cough. ACS will be considered resolved when the patient is no longer hospitalized (unless for reason other than the ACS episode) and none of the additional signs or symptoms above are present (unless for reason other than the ACS).
Up to Year 2
Annualized Rate Vaso Occlusive Crisis (VOC) Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With the Patient) - Hepatic Sequestration
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B)
Hepatic sequestration is defined on the basis of findings of right upper quadrant pain, an enlarged liver, and an acute decrease in hemoglobin concentration (e.g. a decrease in hemoglobin of ~ 2 g/dL). Acute hepatic sequestration will be considered resolved when right upper quadrant pain has returned to baseline (pre-event) levels and hemoglobin has been stable for 24 hrs.
There were no patients with VOC events of hepatic sequestration treated at home. Therefore, there were no observations which met the report criteria.
Up to Year 2
Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Splenic Sequestration
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B)
Splenic sequestration if defined on the basis of findings of left upper quadrant pain, an enlarged spleen, and an acute decrease in hemoglobin concentration (e.g., a decrease in hemoglobin of ~ 2 g/dL). Acute splenic sequestration will be considered resolved when left upper quadrant pain has returned to baseline (pre-event) levels and hemoglobin has been stable for 24 hrs.
Up to Year 2
Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Priapism
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B)
Priapism is defined as an unwanted or painful penile erection lasting at least 30 minutes. The end of an acute priapism event will be when the unwanted erection has resolved for at least 2 hours.
Up to Year 2
Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (VOC-related)
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
This rate was calculated by multiplying the number of hospitalizations and ER visits (VOC-related) by 365 and dividing by the number of days in the observation period.
Units would be something like: hospitalizations and ER visits per year. (Parts A and B)
Up to Year 2
Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (Total)
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
The baseline annualized rate of VOC was defined as the number of VOCs leading to healthcare visit occurring within the last 12 months prior to screening until first dose.
This rate was calculated by multiplying the number of hospitalizations and ER visits (VOC-related) by 365 and dividing by the number of days in the observation period.
Units would be something like: hospitalizations and ER visits per year. (Parts A and B)
Up to Year 2
Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related)
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
The baseline annualized rate of VOC was defined as the number of VOCs leading to healthcare visit occurring within the last 12 months prior to screening until first dose.
This rate was calculated by multiplying the number of days of ER/hospitalizations (both overall and VOC-related) by 365 and dividing by the number of days in the observation period. (Parts A and B)
Years 1 and 2
Annualized Rate of Dactylitis Events
Dactylitis, also known as 'hand-foot syndrome', is a complication of acute vaso-occlusive disease characterized by pain and edema of the digits as well as the dorsum of the hands or feet, or both simultaneously, often accompanied by increased local temperature and erythema.
There were no patients with dactylitis events. Therefore, there were no observations which met the report criteria.
On Treatment, up to Year 2
Absolute Change From Baseline in Hemoglobin
Hemoglobin is a protein that carries oxygen through the body. It attaches to red blood cells, delivers oxygen throughout the body, and transports carbon dioxide back to the lungs. In sickle cell disease, red blood cells are crescent or sickle-shaped due to a genetic mutation, and those sickled red blood cells can clog blood flow, causing debilitating pain and even organ damage.
Baseline, Week 27, Year 2
Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab
Anti-drug antibodies (ADA) are antibodies elicited from therapeutics and they are used to measure immunogenicity.
up to Year 2
Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments
Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Female Participants at Risk of Delayed Puberty at Start Date of Study Treatment
As assessed per Tanner criteria.
The number of Participants Analyzed row refer to participants who have not started puberty and have not had delayed puberty prior to start date of study treatment.
Delayed puberty in females is defined as failure to attain Tanner Stage 2 (for both breast development and pubic hair) by age 13, or absence of menarche by age 15 or within 5 years of attainment of Tanner Stage 2.
Week 51
Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Male Participants at Risk of Delayed Puberty at Start Date of Study Treatment
As assessed per Tanner criteria.
The number of Participants Analyzed row refer to participants who have not started puberty and have not had delayed puberty prior to start date of study treatment.
Delayed puberty in males is defined as failure to attain Tanner Stage 2 (for both genitalia and pubic hair) by age 14.
Week 51
PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A
Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A
A PD marker of crizanlizumab is the ex vivo P-selectin inhibition measured by a surface plasmon resonance assay using human serum samples. Crizanlizumab in serum samples binds to spiked Psel-Ig (P-selectin coupled to Ig) and inhibits its binding to a PSGL1 peptide.
Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B
A PD marker of crizanlizumab is the ex vivo P-selectin inhibition measured by a surface plasmon resonance assay using human serum samples. Crizanlizumab in serum samples binds to spiked Psel-Ig (P-selectin coupled to Ig) and inhibits its binding to a PSGL1 peptide.
Adverse Events by Preferred Term Related to Study Treatment
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject
Adverse events are reported from the first dose of study treatment until end of study treatment Week 103 plus 105 days post-treatment follow-up, up to a maximum timeframe of approximately 2 years and 3.25 months.
Washington D.C.
District of Columbia
20010
United States
University of Florida
Gainesville
Florida
32610
United States
Joe DiMaggio Childrens Hospital
Hollywood
Florida
33021
United States
Childrens Healthcare of Atlanta
Atlanta
Georgia
30342
United States
Childrens Hosp Boston Dept of Hematology
Boston
Massachusetts
02115
United States
Childrens Hospital at Montefiore
The Bronx
New York
10467
United States
Duke University Medical Center
Durham
North Carolina
27710
United States
East Carolina University
Greenville
North Carolina
27834
United States
Childrens Hospital Of Philadelphia
Philadelphia
Pennsylvania
19104-4399
United States
Medical Uni of South Carolina
Charleston
South Carolina
29425
United States
Cook Childrens Medical Center
Fort Worth
Texas
76104
United States
Novartis Investigative Site
Brussels
1000
Belgium
Novartis Investigative Site
Laken
1020
Belgium
Novartis Investigative Site
Liège
4000
Belgium
Novartis Investigative Site
Salvador
Estado de Bahia
41253-190
Brazil
Novartis Investigative Site
Ribeirão Preto
São Paulo
14048-900
Brazil
Novartis Investigative Site
São Paulo
São Paulo
01232-010
Brazil
Novartis Investigative Site
Montreal
Quebec
H3T 1C5
Canada
Novartis Investigative Site
Cali
Valle del Cauca Department
760012
Colombia
Novartis Investigative Site
Montería
230004
Colombia
Novartis Investigative Site
Paris
75015
France
Novartis Investigative Site
Heidelberg
69120
Germany
Novartis Investigative Site
Nagpur
Maharashtra
440009
India
Novartis Investigative Site
Padova
PD
35128
Italy
Novartis Investigative Site
Orbassano
TO
10043
Italy
Novartis Investigative Site
Beirut
1107 2020
Lebanon
Novartis Investigative Site
Tripoli
1434
Lebanon
Novartis Investigative Site
Muscat
123
Oman
Novartis Investigative Site
Palma de Mallorca
Balearic Islands
07120
Spain
Novartis Investigative Site
Barcelona
Catalonia
08035
Spain
Novartis Investigative Site
Madrid
28009
Spain
Novartis Investigative Site
Adana
01330
Turkey (Türkiye)
Novartis Investigative Site
Mersin
33110
Turkey (Türkiye)
Novartis Investigative Site
London
SE1 7EH
United Kingdom
FG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
FG003
Age 2 to <6 Years, 8.5 mg/kg
Age 2 to <6 years, 8.5 mg/kg
FG00050 subjects
FG00113 subjects
FG00240 subjects
FG00314 subjects
COMPLETED
FG00033 subjects
FG00110 subjects
FG00229 subjects
FG00311 subjects
NOT COMPLETED
FG00017 subjects
FG0013 subjects
FG00211 subjects
FG0033 subjects
Type
Comment
Reasons
Pregnancy
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
Death
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Adverse Event
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
Physician Decision
FG0003 subjects
FG0011 subjects
FG0022 subjects
FG0030 subjects
Participant Decision
FG0007 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
Guardian Decision
FG0004 subjects
FG0012 subjects
FG0027 subjects
FG0032 subjects
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
BG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
BG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
BG003
Age 2 to <6 Years, 8.5 mg/kg
Age 2 to <6 years, 8.5 mg/kg
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00050
BG00113
BG00240
BG00314
BG004117
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG00050
BG00113
BG00240
BG003
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00015.00± 1.921
BG0018.87± 1.745
BG002
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
0 - <28 d
Title
Measurements
BG0000
BG0010
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00029
BG0015
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
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
Pharmacokinetics (PK): AUCd15 of Crizanlizumab After First Dose - Part A
The area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) following the first dose. AUCd15 was calculated based on serum concentrations of crizanlizumab.
Pharmacokinetic analysis set 1 - for treated participants with a valid measurement without a protocol deviation with impact.
Posted
Mean
Standard Deviation
hr*ug/mL
Day 1 to Day 15
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
OG003
Age 2 to <6 Years, 8.5 mg/kg
Age 2 to <6 years, 8.5 mg/kg
Units
Counts
Participants
OG00010
OG00111
OG00213
OG003
Title
Denominators
Categories
Title
Measurements
OG00010500± 2290
OG0018180± 1620
OG00220600± 4530
OG003
Primary
Pharmacokinetics (PK) - AUCtau for Serum Crizanlizumab After Multiple Doses - Part A - Steady State
The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1).
Pharmacokinetic analysis set 1 - for treated participants with a valid measurement without a protocol deviation with impact.
Posted
Mean
Standard Deviation
hr*ug/mL
Week 15 - Steady state
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
OG003
Age 2 to <6 Years, 8.5 mg/kg
Age 2 to <6 years, 8.5 mg/kg
Units
Primary
Pharmacokinetics (PK) - Cmax for Crizanlizumab After First Dose and Multiple Doses - Part A - Steady State
The maximum (peak) observed, serum, drug concentration after single or multiple dose administration (mass x volume-1)
Pharmacokinetic analysis set 1 - for treated participants with a valid measurement without a protocol deviation with impact.
Posted
Mean
Standard Deviation
ug/mL
Week 1 (after first dose) and Week 15 (steady state)
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
OG003
Age 2 to <6 Years, 8.5 mg/kg
Age 2 to <6 years, 8.5 mg/kg
Primary
Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab After First Dose - Part A - AUCd15
The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) following the first dose. AUCd15 was calculated based on P-selectin inhibition curves.
Pharmacodynamic analysis set 1 - for treated participants with a valid measurement above the limit of quantitation without a protocol deviation with impact and for measurements that were above the limit of quantitation. (Age 2 to <6 years, 8.5 mg/kg has n = '0' since the values were below the limit of quantitation (BLQ).)
Posted
Mean
Standard Deviation
hr*{Percent} inhibition P-selectin
Day 1 to Day 15
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
OG003
Age 2 to <6 Years, 8.5 mg/kg
Primary
Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab - Part A - AUCtau After Multiple Dose - Steady State
The AUC of %inhibition calculated to the end of a dosing interval (tau) after multiple dose. AUCtau was calculated based on P-selectin inhibition curves.
Pharmacokinetic analysis set 1 - for treated participants with a valid measurement without a protocol deviation with impact.
Posted
Mean
Standard Deviation
hr*{Percent} inhibition P-selectin
Week 15 - Steady state
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
OG003
Age 2 to <6 Years, 8.5 mg/kg
Age 2 to <6 years, 8.5 mg/kg
Primary
Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject
Safety analysis set - all treated participants
Posted
Count of Participants
Participants
Adverse events are reported from the first dose of study treatment until end of study treatment Week 103 plus 105 days post-treatment follow-up, up to a maximum timeframe of approximately 2 years and 3.25 months.
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
OG003
Age 2 to <6 Years, 8.5 mg/kg
Age 2 to <6 years, 8.5 mg/kg
Secondary
Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
The baseline annualized rate of VOC was defined as the number of VOCs leading to healthcare visit occurring within the last 12 months prior to screening until first dose.
This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B)
Full analysis set - for treated participants with a valid measurement without a protocol deviation with impact who had VOC events leading to healthcare visit in clinic/ER/hospital.
Posted
Median
Full Range
VOC events per year
Baseline, Year 1 and Year 2
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
OG003
Secondary
Annualized Rate Vaso Occlusive Crisis (VOC) Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With the Patient)
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B)
Full analysis set - for treated participants with a valid measurement without a protocol deviation with impact who had VOC events treated at home (based on documentation by health care provider following phone contact with the patient.
Posted
Median
Full Range
VOC events per year
Up to Year 2
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
OG003
Age 2 to <6 Years, 8.5 mg/kg
Secondary
Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Uncomplicated Pain Crisis
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B)
Uncomplicated pain crisis is defined as an acute episode of pain with no known cause for pain other than a vaso-occlusive event; and requiring treatment with a parenteral or oral opioids or other parenteral analgesic; but is NOT classified as an acute chest syndrome, hepatic sequestration, splenic sequestration or priapism. The end of an uncomplicated pain crisis will be considered the resolution of acute pain, such that residual pain (or absence of any pain) is considered to be chronic, and the current pain medication regimen is considered to be for this chronic pain.
Full analysis set - for treated participants with uncomplicated pain crisis without a protocol deviation with impact who had VOC events leading to healthcare visit - uncomplicated pain crisis.
Posted
Median
Full Range
VOC events per year
Up to Year 2
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
Secondary
Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Acute Chest Syndrome
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B)
Acute Chest Syndrome (ACS) is defined on the basis of the finding of a new pulmonary infiltrate involving at least one complete lung segment that was consistent with alveolar consolidation, but excluding atelectasis (as indicated by chest X-ray). At least one of the following additional signs or symptoms needs to be present as well: chest pain, a temperature of more than 38.5°C, tachypnea, wheezing or cough. ACS will be considered resolved when the patient is no longer hospitalized (unless for reason other than the ACS episode) and none of the additional signs or symptoms above are present (unless for reason other than the ACS).
Full analysis set - for treated participants with acute chest syndrome without a protocol deviation with impact who had VOC events leading to healthcare visit - acute chest syndrome.
Posted
Median
Full Range
VOC events per year
Up to Year 2
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
Secondary
Annualized Rate Vaso Occlusive Crisis (VOC) Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With the Patient) - Hepatic Sequestration
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B)
Hepatic sequestration is defined on the basis of findings of right upper quadrant pain, an enlarged liver, and an acute decrease in hemoglobin concentration (e.g. a decrease in hemoglobin of ~ 2 g/dL). Acute hepatic sequestration will be considered resolved when right upper quadrant pain has returned to baseline (pre-event) levels and hemoglobin has been stable for 24 hrs.
There were no patients with VOC events of hepatic sequestration treated at home. Therefore, there were no observations which met the report criteria.
Full analysis set - for treated participants with hepatic sequestration without a protocol deviation with impact who had VOC events treated at home (based on documentation by health care provider following phone contact with the patient) - hepatic sequestration. There were no observations which met this criteria.
Posted
Up to Year 2
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Secondary
Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Splenic Sequestration
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B)
Splenic sequestration if defined on the basis of findings of left upper quadrant pain, an enlarged spleen, and an acute decrease in hemoglobin concentration (e.g., a decrease in hemoglobin of ~ 2 g/dL). Acute splenic sequestration will be considered resolved when left upper quadrant pain has returned to baseline (pre-event) levels and hemoglobin has been stable for 24 hrs.
Full analysis set - for treated participants with splenic sequestration with a valid measurement and without a protocol deviation with impact who had VOC events leading to healthcare visit - splenic sequestration. (No patients in the 4th group met this criteria.)
Posted
Median
Full Range
VOC events per year
Up to Year 2
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Secondary
Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Priapism
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
This annualized rate of VOC was calculated by multiplying the number of VOCs by 365 and dividing by the number of days in the observation period. (Parts A and B)
Priapism is defined as an unwanted or painful penile erection lasting at least 30 minutes. The end of an acute priapism event will be when the unwanted erection has resolved for at least 2 hours.
Full analysis set - for treated participants with priapism and with a valid measurement above the limit of quantitation without a protocol deviation with impact who had VOC events leading to healthcare visit - priapism. (No patients in the 1st and 4th group met this criteria.)
Posted
Median
Full Range
VOC events per year
Up to Year 2
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
Secondary
Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (VOC-related)
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
This rate was calculated by multiplying the number of hospitalizations and ER visits (VOC-related) by 365 and dividing by the number of days in the observation period.
Units would be something like: hospitalizations and ER visits per year. (Parts A and B)
Full analysis set - for treated participants with a valid measurement without a protocol deviation with impact who had hospitalizations and ER visits (VOC-related).
Posted
Median
Full Range
hospitalizations and ER visits per year
Up to Year 2
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
OG003
Age 2 to <6 Years, 8.5 mg/kg
Secondary
Annualized Rate of Hospitalizations and Emergency Room (ER) Visits (Total)
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
The baseline annualized rate of VOC was defined as the number of VOCs leading to healthcare visit occurring within the last 12 months prior to screening until first dose.
This rate was calculated by multiplying the number of hospitalizations and ER visits (VOC-related) by 365 and dividing by the number of days in the observation period.
Units would be something like: hospitalizations and ER visits per year. (Parts A and B)
Full analysis set - for treated participants with a valid measurement without a protocol deviation with impact who had hospitalizations and ER visits.
Posted
Median
Full Range
hospitalizations and ER visits per year
Up to Year 2
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
Secondary
Annualized Days of Emergency Room (ER) / Hospitalization (Both Overall and VOC-related)
VOC is defined as pain crises as well as other complicated crises, such as acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration.
The baseline annualized rate of VOC was defined as the number of VOCs leading to healthcare visit occurring within the last 12 months prior to screening until first dose.
This rate was calculated by multiplying the number of days of ER/hospitalizations (both overall and VOC-related) by 365 and dividing by the number of days in the observation period. (Parts A and B)
Full analysis set - for treated participants with a valid measurement without a protocol deviation with impact who had ER/hospitalizations.
Posted
Median
Full Range
Days per year
Years 1 and 2
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
OG003
Age 2 to <6 Years, 8.5 mg/kg
Secondary
Annualized Rate of Dactylitis Events
Dactylitis, also known as 'hand-foot syndrome', is a complication of acute vaso-occlusive disease characterized by pain and edema of the digits as well as the dorsum of the hands or feet, or both simultaneously, often accompanied by increased local temperature and erythema.
There were no patients with dactylitis events. Therefore, there were no observations which met the report criteria.
Safety analysis set - all treated participants who had dactylitis events. There were no observations which met the report criteria.
Posted
On Treatment, up to Year 2
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
OG003
Age 2 to <6 Years, 8.5 mg/kg
Age 2 to <6 years, 8.5 mg/kg
Secondary
Absolute Change From Baseline in Hemoglobin
Hemoglobin is a protein that carries oxygen through the body. It attaches to red blood cells, delivers oxygen throughout the body, and transports carbon dioxide back to the lungs. In sickle cell disease, red blood cells are crescent or sickle-shaped due to a genetic mutation, and those sickled red blood cells can clog blood flow, causing debilitating pain and even organ damage.
Safety analysis set - for treated participants with a valid measurement without a protocol deviation with impact.
Posted
Mean
Standard Deviation
g/L
Baseline, Week 27, Year 2
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
OG003
Age 2 to <6 Years, 8.5 mg/kg
Age 2 to <6 years, 8.5 mg/kg
Secondary
Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab
Anti-drug antibodies (ADA) are antibodies elicited from therapeutics and they are used to measure immunogenicity.
Full analysis set - for treated participants with a valid measurement without a protocol deviation with impact.
Posted
Count of Participants
Participants
up to Year 2
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
OG003
Age 2 to <6 Years, 8.5 mg/kg
Age 2 to <6 years, 8.5 mg/kg
Units
Counts
Secondary
Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments
Safety analysis set - for treated participants with a valid measurement without a protocol deviation with impact
Posted
Count of Participants
Participants
Baseline, up to Year 2
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
OG003
Age 2 to <6 Years, 8.5 mg/kg
Age 2 to <6 years, 8.5 mg/kg
Secondary
Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Female Participants at Risk of Delayed Puberty at Start Date of Study Treatment
As assessed per Tanner criteria.
The number of Participants Analyzed row refer to participants who have not started puberty and have not had delayed puberty prior to start date of study treatment.
Delayed puberty in females is defined as failure to attain Tanner Stage 2 (for both breast development and pubic hair) by age 13, or absence of menarche by age 15 or within 5 years of attainment of Tanner Stage 2.
Full analysis set - only for participants at risk of delayed puberty, (i.e., excludes participants who already reached puberty at study start.)
Posted
Count of Participants
Participants
Week 51
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
OG003
Age 2 to <6 Years, 8.5 mg/kg
Secondary
Growth and Sexual Maturation Assessments (Tanner Stage) - Abnormalities - for Male Participants at Risk of Delayed Puberty at Start Date of Study Treatment
As assessed per Tanner criteria.
The number of Participants Analyzed row refer to participants who have not started puberty and have not had delayed puberty prior to start date of study treatment.
Delayed puberty in males is defined as failure to attain Tanner Stage 2 (for both genitalia and pubic hair) by age 14.
Full analysis set - only for participants at risk of delayed puberty, (i.e., excludes participants who already reached puberty at study start.)
Posted
Count of Participants
Participants
Week 51
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
OG003
Age 2 to <6 Years, 8.5 mg/kg
Secondary
PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A
Pharmacokinetic analysis set 1 - for treated participants with a valid measurement without a protocol deviation with impact.
Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A
A PD marker of crizanlizumab is the ex vivo P-selectin inhibition measured by a surface plasmon resonance assay using human serum samples. Crizanlizumab in serum samples binds to spiked Psel-Ig (P-selectin coupled to Ig) and inhibits its binding to a PSGL1 peptide.
Pharmacodynamic analysis set 1 - for treated participants with a valid measurement without a protocol deviation with impact.
Percent P-selectin Inhibition of Crizanlizumab Prior to Dosing - Part A and B
A PD marker of crizanlizumab is the ex vivo P-selectin inhibition measured by a surface plasmon resonance assay using human serum samples. Crizanlizumab in serum samples binds to spiked Psel-Ig (P-selectin coupled to Ig) and inhibits its binding to a PSGL1 peptide.
Pharmacodynamic analysis set 2 - for treated participants with a valid measurement without a protocol deviation with impact.
Adverse Events by Preferred Term Related to Study Treatment
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject
Safety analysis set - all treated participants
Posted
Count of Participants
Participants
Adverse events are reported from the first dose of study treatment until end of study treatment Week 103 plus 105 days post-treatment follow-up, up to a maximum timeframe of approximately 2 years and 3.25 months.
ID
Title
Description
OG000
Age 12 to <18 Years, 5 mg/kg
Age 12 to <18 years, 5 mg/kg
OG001
Age 6 to <12 Years, 5 mg/kg
Age 6 to <12 years, 5 mg/kg
OG002
Age 6 to <12 Years, 8.5 mg/kg
Age 6 to <12 years, 8.5 mg/kg
OG003
Age 2 to <6 Years, 8.5 mg/kg
Age 2 to <6 years, 8.5 mg/kg
Time Frame
Adverse events are reported from the first dose of study treatment until end of study treatment Week 103 plus 105 days post-treatment follow-up, up to a maximum timeframe of approximately 2 years and 3.25 months.
Description
Not provided
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
Age 12 to < 18 Years, 5 mg/kg
Age 12 to < 18 years, 5 mg/kg
1
50
18
50
46
50
EG001
Age 6 to < 12 Years, 5 mg/kg
Age 6 to < 12 years, 5 mg/kg
0
13
9
13
13
13
EG002
Age 6 to < 12 Years, 8.5 mg/kg
Age 6 to < 12 years, 8.5 mg/kg
0
40
20
40
36
40
EG003
Age 2 to < 6 Years, 8.5 mg/kg
Age 2 to < 6 years, 8.5 mg/kg
0
14
12
14
13
14
EG004
All Participants
All Participants / All arms combined / Total
1
117
59
117
108
117
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (27.1)
Systematic Assessment
EG0002 affected50 at risk
EG0011 affected13 at risk
EG0025 affected40 at risk
EG0031 affected14 at risk
EG0049 affected117 at risk
Bone marrow failure
Blood and lymphatic system disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Mesenteric lymphadenitis
Blood and lymphatic system disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Sickle cell anaemia with crisis
Blood and lymphatic system disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Hyperthermia
General disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Pain
General disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0022 affected40 at risk
EG003
Pyrexia
General disorders
MedDRA (27.1)
Systematic Assessment
EG0002 affected50 at risk
EG0012 affected13 at risk
EG0021 affected40 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0012 affected13 at risk
EG0020 affected40 at risk
EG003
Cholecystitis acute
Hepatobiliary disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0022 affected40 at risk
EG003
Cholelithiasis
Hepatobiliary disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0021 affected40 at risk
EG003
Jaundice
Hepatobiliary disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Anaphylactic reaction
Immune system disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
COVID-19
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0004 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Cellulitis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0023 affected40 at risk
EG003
Cystitis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Device related infection
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Encephalitis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Escherichia urinary tract infection
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Influenza
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Meningitis bacterial
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Metapneumovirus infection
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Parainfluenzae virus infection
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Parvovirus B19 infection
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0021 affected40 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0011 affected13 at risk
EG0024 affected40 at risk
EG003
Pneumonia bacterial
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Pneumonia viral
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Pyelonephritis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Respiratory tract infection viral
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Sepsis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Septic shock
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Thrombophlebitis septic
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Tonsillitis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Viral infection
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0022 affected40 at risk
EG003
Brain herniation
Injury, poisoning and procedural complications
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Infusion related reaction
Injury, poisoning and procedural complications
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Post procedural haemorrhage
Injury, poisoning and procedural complications
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Human rhinovirus test positive
Investigations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Arthritis
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Costochondritis
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Fasciitis
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Myositis
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Brain oedema
Nervous system disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Status migrainosus
Nervous system disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Syncope
Nervous system disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Acute chest syndrome
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Asthma
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Respiratory distress
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Superficial vein thrombosis
Vascular disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (27.1)
Systematic Assessment
EG0008 affected50 at risk
EG0011 affected13 at risk
EG0024 affected40 at risk
EG0033 affected14 at risk
EG00416 affected117 at risk
Leukocytosis
Blood and lymphatic system disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Lymphocytosis
Blood and lymphatic system disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0023 affected40 at risk
EG003
Sickle cell anaemia with crisis
Blood and lymphatic system disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0012 affected13 at risk
EG0022 affected40 at risk
EG003
Thrombocytosis
Blood and lymphatic system disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0024 affected40 at risk
EG003
Bundle branch block right
Cardiac disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Right ventricular enlargement
Cardiac disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Cerumen impaction
Ear and labyrinth disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Ear pain
Ear and labyrinth disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0021 affected40 at risk
EG003
Xerophthalmia
Eye disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (27.1)
Systematic Assessment
EG00010 affected50 at risk
EG0015 affected13 at risk
EG00212 affected40 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0023 affected40 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (27.1)
Systematic Assessment
EG0009 affected50 at risk
EG0013 affected13 at risk
EG0026 affected40 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (27.1)
Systematic Assessment
EG0005 affected50 at risk
EG0011 affected13 at risk
EG0025 affected40 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA (27.1)
Systematic Assessment
EG0002 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Gastrointestinal disorder
Gastrointestinal disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (27.1)
Systematic Assessment
EG0009 affected50 at risk
EG0010 affected13 at risk
EG0025 affected40 at risk
EG003
Odynophagia
Gastrointestinal disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (27.1)
Systematic Assessment
EG00014 affected50 at risk
EG0012 affected13 at risk
EG0024 affected40 at risk
EG003
Chest pain
General disorders
MedDRA (27.1)
Systematic Assessment
EG0003 affected50 at risk
EG0012 affected13 at risk
EG0024 affected40 at risk
EG003
Device related thrombosis
General disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Fatigue
General disorders
MedDRA (27.1)
Systematic Assessment
EG0003 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Hyperthermia
General disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Influenza like illness
General disorders
MedDRA (27.1)
Systematic Assessment
EG0002 affected50 at risk
EG0010 affected13 at risk
EG0022 affected40 at risk
EG003
Malaise
General disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Pain
General disorders
MedDRA (27.1)
Systematic Assessment
EG0002 affected50 at risk
EG0013 affected13 at risk
EG0024 affected40 at risk
EG003
Pyrexia
General disorders
MedDRA (27.1)
Systematic Assessment
EG00012 affected50 at risk
EG0015 affected13 at risk
EG00216 affected40 at risk
EG003
Biliary colic
Hepatobiliary disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Cholelithiasis
Hepatobiliary disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0011 affected13 at risk
EG0023 affected40 at risk
EG003
Hypertransaminasaemia
Hepatobiliary disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Jaundice
Hepatobiliary disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0021 affected40 at risk
EG003
COVID-19
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG00011 affected50 at risk
EG0011 affected13 at risk
EG0024 affected40 at risk
EG003
Conjunctivitis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Eye infection
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0003 affected50 at risk
EG0010 affected13 at risk
EG0023 affected40 at risk
EG003
Influenza
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0002 affected50 at risk
EG0012 affected13 at risk
EG0028 affected40 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0022 affected40 at risk
EG003
Oral candidiasis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Otitis media
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0003 affected50 at risk
EG0010 affected13 at risk
EG0025 affected40 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Rhinitis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Sinusitis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0012 affected13 at risk
EG0021 affected40 at risk
EG003
Suspected COVID-19
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0003 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Tonsillitis
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0012 affected13 at risk
EG0022 affected40 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0009 affected50 at risk
EG0011 affected13 at risk
EG0022 affected40 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0006 affected50 at risk
EG0011 affected13 at risk
EG0021 affected40 at risk
EG003
Viral infection
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0021 affected40 at risk
EG003
Viral upper respiratory tract infection
Infections and infestations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0022 affected40 at risk
EG003
Eye contusion
Injury, poisoning and procedural complications
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Eye injury
Injury, poisoning and procedural complications
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Femur fracture
Injury, poisoning and procedural complications
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Infusion related reaction
Injury, poisoning and procedural complications
MedDRA (27.1)
Systematic Assessment
EG0004 affected50 at risk
EG0012 affected13 at risk
EG0023 affected40 at risk
EG003
Joint injury
Injury, poisoning and procedural complications
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0021 affected40 at risk
EG003
Limb injury
Injury, poisoning and procedural complications
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0022 affected40 at risk
EG003
Nasal injury
Injury, poisoning and procedural complications
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Penis injury
Injury, poisoning and procedural complications
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Skeletal injury
Injury, poisoning and procedural complications
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Vascular access complication
Injury, poisoning and procedural complications
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (27.1)
Systematic Assessment
EG0002 affected50 at risk
EG0011 affected13 at risk
EG0022 affected40 at risk
EG003
Amylase increased
Investigations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Anti factor Xa activity decreased
Investigations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Arterial flow velocity increased
Investigations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (27.1)
Systematic Assessment
EG0003 affected50 at risk
EG0012 affected13 at risk
EG0021 affected40 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA (27.1)
Systematic Assessment
EG0003 affected50 at risk
EG0011 affected13 at risk
EG0021 affected40 at risk
EG003
Blood creatinine increased
Investigations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
C-reactive protein increased
Investigations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Cardiac murmur
Investigations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0021 affected40 at risk
EG003
Epstein-Barr virus test positive
Investigations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Influenza A virus test negative
Investigations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Influenza virus test negative
Investigations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
International normalised ratio increased
Investigations
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Lymphocyte count decreased
Investigations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Polymerase chain reaction negative
Investigations
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
SARS-CoV-2 test negative
Investigations
MedDRA (27.1)
Systematic Assessment
EG00012 affected50 at risk
EG0013 affected13 at risk
EG0020 affected40 at risk
EG003
SARS-CoV-2 test positive
Investigations
MedDRA (27.1)
Systematic Assessment
EG0003 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (27.1)
Systematic Assessment
EG0002 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA (27.1)
Systematic Assessment
EG0003 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Iron deficiency
Metabolism and nutrition disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Vitamin D deficiency
Metabolism and nutrition disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG00011 affected50 at risk
EG0011 affected13 at risk
EG0027 affected40 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG00011 affected50 at risk
EG0012 affected13 at risk
EG0029 affected40 at risk
EG003
Bone infarction
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Mobility decreased
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0012 affected13 at risk
EG0021 affected40 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0003 affected50 at risk
EG0011 affected13 at risk
EG0022 affected40 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0002 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Osteonecrosis
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0004 affected50 at risk
EG0010 affected13 at risk
EG0023 affected40 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG00011 affected50 at risk
EG0013 affected13 at risk
EG00210 affected40 at risk
EG003
Spinal pain
Musculoskeletal and connective tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0021 affected40 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (27.1)
Systematic Assessment
EG0005 affected50 at risk
EG0011 affected13 at risk
EG0021 affected40 at risk
EG003
Headache
Nervous system disorders
MedDRA (27.1)
Systematic Assessment
EG00019 affected50 at risk
EG0014 affected13 at risk
EG00210 affected40 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (27.1)
Systematic Assessment
EG0004 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (27.1)
Systematic Assessment
EG0003 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Suicidal ideation
Psychiatric disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Dysuria
Renal and urinary disorders
MedDRA (27.1)
Systematic Assessment
EG0003 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA (27.1)
Systematic Assessment
EG0003 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Dysmenorrhoea
Reproductive system and breast disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Adenoidal hypertrophy
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Asthma exercise induced
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Bronchospasm
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0005 affected50 at risk
EG0012 affected13 at risk
EG0029 affected40 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0003 affected50 at risk
EG0013 affected13 at risk
EG0021 affected40 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0002 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0003 affected50 at risk
EG0011 affected13 at risk
EG0022 affected40 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0004 affected50 at risk
EG0011 affected13 at risk
EG0021 affected40 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Rhinitis allergic
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected13 at risk
EG0021 affected40 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA (27.1)
Systematic Assessment
EG0005 affected50 at risk
EG0011 affected13 at risk
EG0022 affected40 at risk
EG003
Nail dystrophy
Skin and subcutaneous tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0004 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0001 affected50 at risk
EG0011 affected13 at risk
EG0022 affected40 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Hypertension
Vascular disorders
MedDRA (27.1)
Systematic Assessment
EG0002 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 at risk
EG003
Pallor
Vascular disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected13 at risk
EG0020 affected40 at risk
EG003
Phlebitis
Vascular disorders
MedDRA (27.1)
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected13 at risk
EG0020 affected40 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 (i.e., data from all sites) in the clinical trial.