A Study to Evaluate Crovalimab in People With Antiphospholipid Syndrome (APS)
Not Applicable
Not yet recruiting
- Conditions
- Antiphospholipid Syndrome
- Interventions
- Registration Number
- NCT07172022
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
The main purpose of this study is to evaluate the efficacy of crovalimab compared with placebo as an add-on therapy to vitamin K antagonist (VKA) in participants with APS.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 300
Inclusion Criteria
- Age ≥18 years and ≤70 years, and body weight ≥40 kilograms (kg), at the time of signing Informed Consent Form
- Vaccination against N. meningitidis, H. influenzae type B, and S. pneumoniae
- Participants classified with APS who have experienced at least two prior arterial and/or venous thrombotic events, based on the 2023 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) criteria, positive for at least two of the following: lupus anticoagulant (LAC) test, anticardiolipin antibodies (aCL), anti-β2-glycoprotein 1 antibodies (aβ2GP1)
- Participants receiving corticosteroids, antimalarial treatment, non-biologic disease-modifying rheumatic drugs, statins, and low dose aspirin must be on a stable dose prior to the first dose of study treatment
- Willingness and ability to comply with a VKA regimen titrated to a therapeutic target internal normalized ratio (INR)
- Agreement to adhere to the contraception requirements
Exclusion Criteria
- Pregnant or breastfeeding, or intention of becoming pregnant during the study or within the time frame in which contraception is required
- Treatment with investigational therapy, complement inhibitor, and/or other immune-suppressive biologic therapy within 5 half-lives of that agent prior to screening visit, or plans to participate in another investigational trial
- Presence of another systemic autoimmune disease that is unstable and requires additional treatment, and constitutes the principal illness and may impact evaluation of the concurrent APS
- Inadequate renal and hepatic function
- Uncontrolled hyperlipidemia and/or hypertension, known diabetes mellitus, and/or serious infection requiring hospitalization or antibiotics prior to Week 1 Day 1
- History or condition associated with increased bleeding risk
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Crovalimab + VKA Crovalimab Participants will receive 3 loading doses of crovalimab, 680 milligrams (mg) or 1020 mg, as a subcutaneous (SC) injection based on their body weight (BW) at Weeks 1, 2 and 3 followed by maintenance doses, every 4 weeks (Q4W) from Week 5 until arterial thrombosis, venous thromboembolism or cardiovascular death. Participants will also receive VKA with a target internal normalized ratio (INR) based on investigator's discretion and local guidance. Crovalimab + VKA VKA Participants will receive 3 loading doses of crovalimab, 680 milligrams (mg) or 1020 mg, as a subcutaneous (SC) injection based on their body weight (BW) at Weeks 1, 2 and 3 followed by maintenance doses, every 4 weeks (Q4W) from Week 5 until arterial thrombosis, venous thromboembolism or cardiovascular death. Participants will also receive VKA with a target internal normalized ratio (INR) based on investigator's discretion and local guidance. Placebo + VKA Placebo Participants will receive 3 doses of placebo as a SC injection with equal volume dosing as the weight-based crovalimab at Weeks 1, 2, and 3, followed by Q4W doses, as a SC injection, from Week 5 until arterial thrombosis, venous thromboembolism, or cardiovascular death. Participants will also receive VKA with a target INR based on the investigator's discretion and local guidance. Placebo + VKA VKA Participants will receive 3 doses of placebo as a SC injection with equal volume dosing as the weight-based crovalimab at Weeks 1, 2, and 3, followed by Q4W doses, as a SC injection, from Week 5 until arterial thrombosis, venous thromboembolism, or cardiovascular death. Participants will also receive VKA with a target INR based on the investigator's discretion and local guidance.
- Primary Outcome Measures
Name Time Method Time From Randomization to First Occurrence of Objectively Confirmed Arterial Thrombosis, Venous Thromboembolism or Cardiovascular Death Up to approximately 4.5 years
- Secondary Outcome Measures
Name Time Method Time From Randomization to the First Occurrence of Objectively Confirmed Venous Thromboembolism Up to approximately 4.5 years Time From Randomization to the First Occurrence of Objectively Confirmed Arterial Thrombosis Up to approximately 4.5 years Percentage of Participants With Adverse Events (AEs) With Severity Determined According to the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0) Up to approximately 4.5 years Percentage of Participants With Injection Site Reactions and Hypersensitivity Up to approximately 4.5 years Percentage of Participants With Infections and Severity of Infection Up to approximately 4.5 years Percentage of Participants With AEs Leading to Study Drug Discontinuation Up to approximately 4.5 years Serum Concentrations of Crovalimab Over Time Up to approximately 4.5 years