Haematological Disorders
Conditions
Interventions
Crizanlizumab SEG101 at 5 mg per kg
Placebo Comparator
Crizanlizumab SEG101 at 7.5 mg per kg
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
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 and older 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 include: a. Pain crisis defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion, b. a visit to a medical facility and/or healthcare professional, c. and receipt of oral/parenteral opioids or parenteral nonsteroidal anti-inflammatory drug (NSAID) analgesia As well as other complicated crises, such as acute chest syndrome, priapism, and hepatic or splenic sequestration (see Section 8.3.1 for further definition) 5. If receiving HU/HC or L-glutamine or erythropoietin stimulating agent , must have been receiving the drug for at least 6 months prior to Screening visit and plan to continue taking 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 6. Patients must meet the following central laboratory values at the screening visit: Absolute Neutrophil Count =1.0 x 109/L, Platelet count =75 x 109/L, Hemoglobin: for adults (Hb) =4.0 g/dL and for adolescents (Hb) =5.5 g/dL, Glomerular filtration rate = 45 mL/min/1.73 m2 using CKD-EPI formula in adults, and Shwartz formula in adolescents, Direct (conjugated) bilirubin < 2.0 x ULN, Alanine transaminase (ALT) < 3.0 x ULN 7. ECOG performance status =2.0 for adults and Karnofsky = 50% for adolescents 8. Received standard age-appropriate care for SCD, including an up-to-date record of immunizations, as per local requirements
Exclusion criteria
Exclusion criteria: 1. History of stem cell transplant 2. Received blood products within 30 days of Week 1 Day 1 dosing 3. Participating in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes) and/or planning on undergoing an exchange transfusion and/or plasmapheresis during the duration of the study; episodic transfusion in response to worsened anemia or VOC is permitted 4. 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 5. Use of therapeutic anticoagulation or antiplatelet therapy (other than aspirin or NSAIDs) within the 10 days prior to Week 1 Day 1 dosing. Note: Prophylactic anticoagulant dose is permitted, as per local guidelines 6. 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 7. Pregnant females or females who have given birth within the past 90 days or who are breastfeeding 8. 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. Highly effective contraception methods include: • Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment • Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that patient • Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment 9. Any documented history of a clinical stroke or intracranial hemorrhage, or an uninvestigated neurologic finding within the past 12 months before screening visit. Silent infarct only present on imaging is allowed 10. Clinically significant bleeding disorder 11. Planning to undergo a major surgical procedure during the duration of the study 12. Hospitalized at Screening 13. Patient with active HIV infection (detectable viral load) 14. Patients with active Hepatitis B infection (HBsAg positive) will be excluded Note: Patients with antecedent but no active Hepatitis B (i.e. anti-HBc positive, HBsAg and HBV-DNA negative) are eligible 15. Positive test for hepatitis C ribonucleic acid (HCV RNA) Note: Patients in whom HCV infection resolved spontaneously (positive HCV antibodies without detectable HC
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare the efficacy of 7.5 mg/kg of crizanlizumab versus placebo on the annualized rate of VOC leading to healthcare visit, in addition to standard of care To compare the efficacy of 5.0 mg/kg of crizanlizumab versus placebo on the annualized rate of VOC leading to healthcare visit, in addition to standard of care | — |
Secondary
| Measure | Time frame |
|---|---|
| Key secondary objective: To compare the efficacy of 7.5 mg/kg versus placebo on the annualized rate of all VOCs (managed at home + leading to healthcare visit) To compare the efficacy of 5.0 mg/kg versus placebo on the annualized rate of all VOCs (managed at home + leading to healthcare visit) To assess the number of days with VOC leading to healthcare visit in each group To assess rate of subjects free from VOC leading to healthcare visit in each group To assess the time to first and second VOC leading to healthcare visit in each group Healthcare resource utilization (visits to clinic, Emergency room (ER) and hospitalizations) in each group versus placebo To assess SCD-related renal damage in each group To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg To characterize the pharmacodynamic (PD) (P-selectin inhibition) of crizanlizumab at 5.0 and 7.5 mg/kg To assess efficacy, safety and immunogenicity of crizanlizumab over the study period (treatment of 5 years + 105 days of follow-up) (taking into account potential treatment switch after primary analysis) | — |
Countries
Ghana, Kenya, South Africa
Contacts
Public ContactClinical Disclosure Officer Clinical Disclosure Officer
Clinical Disclosure Officer
Outcome results
None listed