Purpose

The purpose of this study is to compare the efficacy and safety of 2 doses of crizanlizumab (5.0 mg/kg and 7.5 mg/kg) versus placebo in adolescent and adult sickle cell disease (SCD) patients with history of vaso-occlusive crisis (VOC) leading to healthcare visit.

Condition

Eligibility

Eligible Ages
Over 12 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Written informed consent must be obtained prior to any screening procedures
  2. Male or female patients aged 12 years and older on the day of signing informed consent. Adolescent include patients aged 12 to 17 years old and adults ≥ 18 years
  3. Confirmed diagnosis of SCD by hemoglobin electrophoresis or high performance liquid chromatography (HPLC) [performed locally]. All SCD genotypes are eligible, genotyping is not required for study entry
  4. Experienced at least 2 VOCs leading to healthcare visit within the 12 months prior to screening visit as determined by medical history. Prior VOC leading to healthcare visit must resolve at least 7 days prior to Week 1 Day 1 and must include:
  5. Pain crisis defined as an acute onset of pain for which there is no other medically determined explanation other than vaso- occlusion -
  6. which requires a visit to a medical facility and/or healthcare professional,
  7. and receipt of oral/parenteral opioids or parenteral nonsteroidal anti-inflammatory drug (NSAID) analgesia Acute chest syndrome (ACS), priapism and hepatic or splenic sequestration will be considered VOC in this study
  8. If receiving HU/HC or L-glutamine (local HA approved medicinal product), must have been receiving the drug for at least 6 months and at a stable dose for at least 3 months prior to Screening visit and plan to continue taking it at the same dose and schedule until the subject has reached one year of study treatment. Patients who have not been receiving such drug must not have received it for at least 6 months prior to Screening visit to be included. Patients must have evidence of insufficient control of acute pain, such as at least one VOC leading to healthcare visit while on HU/HC or L-Glutamine treatment. If receiving erythropoietin stimulating agent, must have been receiving the drug for at least 6 months prior to Screening visit and plan to continue taking the treatment to maintain stable Hb levels at least until the subject has reached one year of study treatment
  9. Patients must meet the following central laboratory values prior to Week 1 Day 1:
  10. Absolute Neutrophil Count ≥1.0 x 109/L
  11. Platelet count ≥75 x 109/L
  12. Hemoglobin: for adults (Hb) ≥4.0 g/dL and for adolescents (Hb) ≥5.5 g/dL
  13. Glomerular filtration rate ≥ 45 mL/min/1.73 m2 using CKD-EPI formula in adults, and Shwartz formula in adolescents
  14. Direct (conjugated) bilirubin < 2.0 x ULN
  15. Alanine transaminase (ALT) < 3.0 x ULN
  16. ECOG performance status ≤2.0 for adults and Karnofsky ≥ 50% for adolescents

Exclusion Criteria

  1. History of stem cell transplant.
  2. Participating in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes) and/or planning on undergoing an exchange transfusion during the duration of the study; episodic transfusion in response to worsened anemia or VOC is permitted.
  3. Contraindication or hypersensitivity to any drug or metabolites from similar class as study drug or to any excipients of the study drug formulation. 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.
  4. Received active treatment on another investigational trial within 30 days (or 5 half-lives of that agent, whichever is greater) prior to Screening visit or plans to participate in another investigational drug trial.
  5. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant unless they are using highly effective methods of contraception during dosing and for 15 weeks after stopping treatment.
  6. Concurrent severe and/or uncontrolled medical conditions which, in the opinion of the Investigator, could cause unacceptable safety risks or compromise participation in the study.
  7. History or current diagnosis of ECG abnormalities indicating significant risk of safety such as:
  8. Concomitant clinically significant cardiac arrhythmias (e.g ventricular tachycardia), and clinically significant second or third degree AV block without a pacemaker
  9. History of familial long QT syndrome or know family history of Torsades de Pointes
  10. Not able to understand and to comply with study instructions and requirements.
  11. Received prior treatment with crizanlizumab or other selectin targeting agent

Other protocol-defined Inclusion/Exclusion may apply.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Double-blind Study

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Crizanlizumab (SEG101) at 5.0 mg/kg
Participants will receive Crizanlizumab (SEG101) at 5.0 mg/kg
  • Drug: Crizanlizumab (SEG101)
    Crizanlizumab will be supplied in single use 10 mL glass vials at a concentration of 10 mg/mL. One vial contains 100 mg of crizanlizumab. This is a concentrate for solution for infusion IV.
    Other names:
    • SEG101
Experimental
Crizanlizumab (SEG101) at 7.5 mg/kg
Participants will receive Crizanlizumab (SEG101) at 7.5 mg/kg
  • Drug: Crizanlizumab (SEG101)
    Crizanlizumab will be supplied in single use 10 mL glass vials at a concentration of 10 mg/mL. One vial contains 100 mg of crizanlizumab. This is a concentrate for solution for infusion IV.
    Other names:
    • SEG101
Placebo Comparator
Placebo
Participants will receive the placebo drug.
  • Drug: Placebo
    Placebo will be supplied in single use 10 mL glass vials at a concentration of 10 mg/mL. One vial contains 100 mg of placebo. This is a concentrate for solution for infusion IV.

Recruiting Locations

Boston Medical Center
Boston, Massachusetts 02118
Contact:
Anthony Akinbami
617-638-9136
Anthony.Akinbami@bmc.org

More Details

Status
Recruiting
Sponsor
Novartis Pharmaceuticals

Study Contact

Novartis Pharmaceuticals
1-888-669-6682
novartis.email@novartis.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.