Sickle cell disease (SCD)
Conditions
Interventions
Eligible patients will be randomized 1:1 to receive either crovalimab or placebo in addition to their current SCD therapy. Randomisation is via the IXRS system. Patients in both treatment arms will re
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed ICF or Assent Form (as determined by patient’s age and individual site and country standards) 2. Age =12 to =55 years 3. Body weight =40 kg 4. Male or female with confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSß0 (SCD genotype of sickle cell beta zero thalassemia) 5. Two or more (=2) to =10 documented VOEs in the 12 months prior to randomization 6. If receiving concurrent SCD-directed therapy, the patient must have been on a stable dose for a minimum of 3 months prior to study enrollment. There should be no plans to modify the patients’ dosing throughout the study duration, other than for safety reasons. 7. If receiving erythropoietin, the patient must have been prescribed this medication for the preceding 3 months and be dose-stabilized for at least 3 months prior to study enrollment 8. Vaccination against N. meningitides, vaccinations against H. influenza type B and S. pneumonia 9. Patients who have been vaccinated (partially or in full) against SARS-CoV-2 with a locally approved vaccine are eligible to be enrolled in the study, 3 days or longer after inoculation 10. Adequate hepatic and renal function 11. For women of childbearing potential, agreement to remain abstinent or use contraception during the treatment period and for 6 months after the final dose of study treatment
Exclusion criteria
Exclusion criteria: 1. History of hematopoietic stem cell transplant 2. Participating in a chronic transfusion program and/or planning on undergoing an exchange transfusion during the duration of the study 3. History of hypersensitivity, allergic, or anaphylactic reactions to any ingredient contained in the study treatment 4. Received active treatment on another investigational trial within 28 days (or within five half-lives of that agent, whichever is greater) prior to screening visit, or plans to participate in another investigational drug trial 5. Hemoglobin <6 g/dl 6. Known or suspected hereditary complement deficiency 7. Active systemic bacterial, viral, or fungal infection within 14 days before first drug administration 8. Presence of fever (=38 degrees Celsius) within 7 days before the first drug administration 9. Immunized with a live attenuated vaccine within 1 month before first drug administration 10. Pregnant or breastfeeding, or intending to become pregnant during the study or within 6 months after the final dose of study treatment 11. Known HIV infection with documented CD4 count <200 cells/microliter within 24 weeks prior to screening 12 History of N. meningitidis infection within the prior 6 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures as of 07/03/2023: Annualized rate of medical facility VOEs (AVR) measured using data recorded in the electronic case report forms (eCRFs) from Baseline to Week 49 Previous primary outcome measures: Annualized rate of medical facility VOEs (AVR) up to 48 weeks. A medical facility VOE is defined as: 1. An uncomplicated medical facility VOE (defined as an acute episode of pain lasting at least 2 hours and occurring at least 3 days after return to the patient’s chronic baseline pain levels, with no other medically determined cause other than a VOE that requires a medical facility visit and treatment with oral or parenteral opioids, parenteral nonsteroidal anti-inflammatory drugs [NSAIDs], or ketamine), OR 2. Acute chest syndrome (ACS), hepatic or splenic sequestration, or priapism requiring a visit to a medical facility. Patients complete an e-diary and an HVQ sickle cell pain crisis questionnaire which will be reviewed and analysed by clinical scientists | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 07/03/2023: All outcomes will be measured from data recorded in the electronic case report forms (eCRFs) unless otherwise stated: 1. Annualized rate of home VOEs from Baseline to Week 49 2. Annualized rate of uncomplicated medical facility VOEs from Baseline up to Week 49 3. Annualized rate of acute chest syndrome (ACS) from Baseline up to Week 49 4. Annualized rate of days hospitalized for medical facility VOE from Baseline up to Week 49 5. Annualized rate of days hospitalized for treatment of Non-VOE complications of SCD from Baseline up to Week 49 6. Time to first medical facility VOE from randomization from Baseline up to Week 49 7. Change in urinary albumin-creatinine ratio from Baseline up to Week 49 8. Change in tricuspid regurgitant jet velocity (TRV) from Baseline to Week 49 9. Percentage of participants with TRV >2.5 m/s at Week 49 10. Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Score in adults from Baseline to Week 49 11. Percentage of participants with adverse events (AEs) up to 91 weeks 12. Serum concentrations of crovalimab over time from Baseline up to Week 49 13. Percentage of participants with anti-drug antibodies to crovalimab in serum from Baseline up to Week 49 Previous secondary outcome measures: 1. Annualized rate of home VOE captured on the patient's handheld device provided and questionnaires at baseline to Week 49 2. Annualized rate of uncomplicated medical facility VOE captured in the patients notes at baseline to Week 49 3. Annualized rate of acute chest syndrome (ACS) captured in the patients notes at baseline to Week 49 4. Annualized rate of days hospitalized for medical facility VOE captured in the patients notes at baseline to Week 49 5. Annualized rate of days hospitalized for treatment of non-VOE complications of SCD captured in the patients notes at baseline to Week 49 6. Hematologic measures measured using routine safety bloods from base | — |
Countries
Brazil, England, France, Italy, Spain, Turkey, United Kingdom
Outcome results
None listed