A PHASE IB, RANDOMIZED, PLACEBO-CONTROLLED STUDY EVALUATING THE SAFETY, PHARMACOKINETICS, PHARMACODYNAMICS, AND EFFICACY OF CROVALIMAB FOR THE MANAGEMENT OF ACUTE UNCOMPLICATED VASO*OCCLUSIVE EPISODES (VOE) IN PATIENTS WITH SICKLE CELL DISEASE (SCD)
- Conditions
- sickle cell disease (SCD) / sickle cell anemia1003815810005330
- Registration Number
- NL-OMON53925
- Lead Sponsor
- Roche Nederland B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 3
-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.
- >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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary outcome = safety:<br /><br>- Incidence and severity of adverse events<br /><br>- Change from baseline in targeted vital signs and clinical laboratory test<br /><br>results<br /><br>- Incidence and severity of infusion-related reactions and hypersensitivity</p><br>
- Secondary Outcome Measures
Name Time Method <p>Pharmacokinetics (PK)<br /><br>Serum concentrations of crovalimab over time<br /><br>Pharmacodynamics (PD)<br /><br>Change over time in PD biomarkers<br /><br>Exploratory Biomarker<br /><br>Change over time in exploratory biomarkers<br /><br><br /><br>Efficacy:<br /><br>-Time to VOE improvement<br /><br>-Time to readiness for discharge<br /><br>-Time to hospital discharge<br /><br>-Total cumulative opioid dose (MEU/kg)<br /><br>-Time to discontinuation of all parenteral opioids<br /><br>-Change in pain score at hospital discharge (NRS: 0-10)<br /><br>-Time to confirmed decrease in pain score of at least 2 points sustained for a<br /><br>minimum of 6 hours<br /><br>-Proportion of patients requiring intensive care unit (ICU)<br /><br>-Proportion of patients requiring blood transfusion<br /><br>-Proportion of patients who develop ACS up to Day 28<br /><br>-Re-admission within 28 days of discharge of the primary hospitalization</p><br>