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-NL

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 serotypes A, C, W, and Y
• 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 322 days (approximately 10.5 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
• 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 322 days (approximately 10.5 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. Up to 322 days<br>2. Baseline to 84 days<br>3. Up to 84 days<br><br>

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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