sickle cell disease (SCD) / sickle cell anemia
Conditions
Interventions
The investigational medicinal products for this study are crovalimab IV and
placebo IV (2:1). Patients in this study will receive a single IV dose of
crovalimab or placebo according to a weight-base
Sponsors
Roche Nederland B.V.
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: -Age 12-55 years; >=40 kg at screening -Confirmed diagnosis of SCD (HbSS or HbSβ0) -Diagnosis of an acute uncomplicated VOE defined as an acute episode of pain with no other medically determined cause, requiring admission to a hospital and treatment with parenteral opioids -Ability to receive the first dose of study drug within 12 hours from initial evaluation in the ER/ED -Vaccinations against Neisseria meningitidis, Haemophilus influenzae type B, and Streptococcus pneumoniae -Adequate hepatic and renal function -Hemoglobin >= 5 g/dL; Platelet count >= 100,000/µL -Patients receiving sickle cell therapies must be on a stable dose for 28 days prior to VOE presentation -For women of childbearing potential: agreement to remain abstinent or use contraception Eligibility criteria are split between an Initial Screening (#1) and VOE Screening (#2) in the protocol. If an initial screening is not completed, all criteria listed must be assessed at VOE presentation.
Exclusion criteria
Exclusion criteria: - >10 VOE events in the past 12 months requiring a medical facility/ healthcare provider visit - VOE ongoing for >48 hours prior to presenting to the ER/ED or acute care facility - Pain atypical of an acute uncomplicated VOE or other alternative cause or explanation for pain Evidence of ACS; Acute pain related to avascular necrosis, hepatic or splenic sequestration, or priapism - Evidence or high suspicion of a severe systemic infection; Presence of fever >= 38 °C (100.4 °F) - Transfusion within 3 months or as part of BSC regimen for the current VOE, or participation in a chronic transfusion protocol - Presentation with a critical illness necessitating ICU or critical care admission - History of N. meningitidis infection within 6 months prior to VOE presentation - Major surgery and/or hospitalization for any reason within 30 days prior to VOE presentation - Pregnant or breastfeeding, or intending to become pregnant during the study or within 10.5 months after the study drug administration
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary outcome = safety: - Incidence and severity of adverse events - Change from baseline in targeted vital signs and clinical laboratory test results - Incidence and severity of infusion-related reactions and hypersensitivity | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK) Serum concentrations of crovalimab over time Pharmacodynamics (PD) Change over time in PD biomarkers Exploratory Biomarker Change over time in exploratory biomarkers Efficacy: -Time to VOE improvement -Time to readiness for discharge -Time to hospital discharge -Total cumulative opioid dose (MEU/kg) -Time to discontinuation of all parenteral opioids -Change in pain score at hospital discharge (NRS: 0-10) -Time to confirmed decrease in pain score of at least 2 points sustained for a minimum of 6 hours -Proportion of patients requiring intensive care unit (ICU) -Proportion of patients requiring blood transfusion -Proportion of patients who develop ACS up to Day 28 -Re-admission within 28 days of discharge of the primary hospitalization | — |
Countries
Netherlands
Outcome results
None listed