Sickle Cell Disease (SCD)Phase 2NCT03474965
Study of Dose Confirmation and Safety of Crizanlizumab in Pediatric Sickle Cell Disease Patients
A Phase 2 study testing Crizanlizumab in people with Sickle Cell Disease (SCD), run by Novartis Pharmaceuticals at 35 sites in 14 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Sickle Cell Disease (SCD)
- What is being tested?
- Crizanlizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 117 participants
- Where
- 35 sitesin 14 countries
- Study dates
- 1 Oct 2018to 6 Nov 2024
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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.
Show all 22Show fewer
- 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.
Trial locations and contacts
35 sites in 14 countries.
35 sites in 14 countries
United States12 sites
Childrens Healthcare of Atlanta
Atlanta, Georgia, 30342
University Of Alabama
Birmingham, Alabama, 35233
Childrens Hosp Boston Dept of Hematology
Boston, Massachusetts, 02115
Medical Uni of South Carolina
Charleston, South Carolina, 29425
Duke University Medical Center
Durham, North Carolina, 27710
Cook Childrens Medical Center
Fort Worth, Texas, 76104
University of Florida
Gainesville, Florida, 32610
East Carolina University
Greenville, North Carolina, 27834
Joe DiMaggio Childrens Hospital
Hollywood, Florida, 33021
Childrens Hospital Of Philadelphia
Philadelphia, Pennsylvania, 19104-4399
Childrens Hospital at Montefiore
The Bronx, New York, 10467
Childrens National Hospital
Washington D.C., District of Columbia, 20010
Belgium3 sites
Novartis Investigative Site
Brussels, 1000
Novartis Investigative Site
Laken, 1020
Novartis Investigative Site
Liège, 4000
Brazil3 sites
Novartis Investigative Site
Ribeirão Preto, São Paulo, 14048-900
Novartis Investigative Site
Salvador, Estado de Bahia, 41253-190
Novartis Investigative Site
São Paulo, São Paulo, 01232-010
Spain3 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Madrid, 28009
Novartis Investigative Site
Palma de Mallorca, Balearic Islands, 07120
Colombia2 sites
Novartis Investigative Site
Cali, Valle del Cauca Department, 760012
Novartis Investigative Site
Montería, 230004
Italy2 sites
Novartis Investigative Site
Orbassano, TO, 10043
Novartis Investigative Site
Padova, PD, 35128
Lebanon2 sites
Novartis Investigative Site
Beirut, 1107 2020
Novartis Investigative Site
Tripoli, 1434
Turkey (Türkiye)2 sites
Novartis Investigative Site
Adana, 01330
Novartis Investigative Site
Mersin, 33110
About this study
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
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.
Read the 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
- Sickle Cell Disease (SCD)
- Being tested
- Crizanlizumab
- Keywords
- SEG101, Sickle cell disease, SCD, crizanlizumab, pediatric, pharmacokinetic, P-selectin, Covid-19, Coronavirus disease 2019
- Medical subject headings
- Anemia, Sickle Cell, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CrizanlizumabDrug
Also called SEG101
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Crizanlizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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)
Measured: 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.
Measured: 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.
Measured: Week 15 - Steady state
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
Measured: 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.
Secondary outcomes (21)
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)
Measured: 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)
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: up to Year 2
Notable On-treatment Findings From the Electrocardiogram (ECG) Assessments
QTcF = QT interval corrected by Fridericia's formula QTcB = Corrected QT interval Bazett's Formula QT = QT interval PR = PR interval QRS = QRS interval RR = RR interval HR = heart rate
Measured: Baseline, up to Year 2
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.
Measured: 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.
Measured: Week 51
PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Part A
Measured: Week 3, Week 7, Week 11, Week 15, Week 19, Week 23, Week 27, Week 31, Week 35, Week 39, Week 43, Week 47 and Week 51 (Day 1, 0 hr (pre-dose))
PK Pre-dose Concentrations of Crizanlizumab Prior to Each Study Drug Dose - Parts A and B
Measured: Week 3, Week 7, Week 11, Week 15, Week 19, Week 23, Week 27, Week 31, Week 35, Week 39, Week 43, Week 47 and Week 51 (0 hr (pre-dose))
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.
Measured: Weeks 3, 7, 11,15, 19, 23, 27, 31, 35, 39, 43,47,51 (Day 1, 0 hr (pre-dose))
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.
Measured: Weeks 3, 7, 11,15, 19, 23, 27, 31, 35, 39, 43,47,51 (Day 1, 0 hr (pre-dose))
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
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2018
- Study start1 Oct 2018
- Primary completion6 Nov 2024
- Study completion6 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell Disease (SCD)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03474965
- Sponsor's protocol ID
- CSEG101B2201
- Other IDs
- 2017-001747-12, 2017
- Status last verified
- Oct 2025
- First submitted
- 16 Mar 2018
- Last updated
- 16 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
Publications
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.
PubMed 34922648