A Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Crovalimab for the Management of Acute Uncomplicated Vaso-Occlusive Episodes in Patients with Sickle Cell Disease

Phase 1

Conditions: Sickle cell disease (SCD)
vaso-occlusive episodes (VOE) in SCD
MedDRA version: 21.0Level: PTClassification code 10040644Term: Sickle cell diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 20.0Level: LLTClassification code 10072397Term: Vaso-occlusive crisisSystem Organ Class: 100000004851
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2020-004840-27-FR

Lead Sponsor: F.Hoffmann-La Roche Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 30

Inclusion Criteria

• Signed ICF or Assent Form (as determined by patient’s age and individual site and country standards)
• Age >=12 to =<55 years
• Body weight >=40 kg
• Confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSß0 (SCD genotype of sickle cell beta zero thalassemia)
• Vaccination against Neisseria meningitidis
• Vaccinations against H. influenzae type B and S. pneumoniae
• Diagnosis of an acute uncomplicated VOE, that requires admission to a hospital/acute medical facility and treatment with parenteral opioid analgesics
• 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
• For female patients of childbearing potential, an agreement to remain abstinent or use contraception for 6 months after the dose of study treatment

Are the trial subjects under 18? yes
Number of subjects for this age range: 8
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 22
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• More than 10 VOEs within the last 12 months prior to presentation, that have required a medical facility visit
• Pain related to the current VOE ongoing for >48 hours
• Acute pain related to avascular necrosis, hepatic or splenic sequestration, or priapism
• Pain atypical of an acute uncomplicated VOE
• Evidence of or suspicion of ACS
• Evidence or high suspicion of a severe systemic infection
• Major surgery and/or hospitalization for any reason within 30 days prior to VOE presentation
• History of Neisseria meningitidis infection within 6 months prior
• Known HIV infection with a documented CD4 count <200 cells/µL
• Transfusion or receipt of blood products within 3 months or current participation in a chronic transfusion protocol
• Immunized with a live attenuated vaccine within 30 days
• History of hematopoietic stem cell transplant
• Known or suspected hereditary complement deficiency
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 6 months after the study drug administration
• Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within the prior 28 days or within five half-lives of that investigational product, whichever was greater

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • To evaluate the safety of crovalimab compared with placebo;Secondary Objective: • To evaluate the pharmacokinetics (PK) of crovalimab<br>• To evaluate the pharmacodynamics (PD) of crovalimab <br>• To evaluate the efficacy of crovalimab compared with placebo<br>• To evaluate the immune response to crovalimab<br>;Primary end point(s): 1. Incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0)<br>2. Change from baseline in targeted vital signs and clinical laboratory test results<br>3. Incidence and severity of infusion-related reactions and hypersensitivity<br>;Timepoint(s) of evaluation of this end point: 1-3. Up to 84 days

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Serum concentrations of crovalimab over time<br>2. Relationships between drug exposure and pharmacodynamics, efficacy or safety endpoints of crovalimab<br>3. Change over time in PD markers (CH50, free C5, sC5b-9)<br>4. Time to improvement of the primary acute uncomplicated VOE from baseline<br>5. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study <br>;Timepoint(s) of evaluation of this end point: 1-3. Baseline to Day 84<br>4. Baseline to hospital discharge (up to 84 days)<br>5. Baseline to Day 84<br>

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