Antiphospholipid Syndrome
Conditions
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.
Interventions
DRUGCrovalimab
Crovalimab will be administered at a dose of 680 mg (for participants with BW ≥ 40 kilograms \[kg\] to \< 100 kg) or 1020 mg (for participants with BW ≥ 100 kg), as a SC injection, at Weeks 1, 2, and 3 and Q4W from Week 5 onwards.
DRUGPlacebo
Placebo matching crovalimab will be administered as per the schedule specified in the respective arm.
DRUGVKA
Dose administration of VKA will be in accordance with the local prescribing information for the respective product. The VKA regimen will be titrated to a therapeutic target INR based on investigator discretion and local standard of care (SOC).
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time From Randomization to First Occurrence of Objectively Confirmed Arterial Thrombosis, Venous Thromboembolism or Cardiovascular Death | Up to approximately 4.5 years |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Time From Randomization to the First Occurrence of Objectively Confirmed Venous Thromboembolism | Up to approximately 4.5 years |
| Serum Concentrations of Crovalimab Over Time | Up to approximately 4.5 years |
| Time From Randomization to the First Occurrence of Objectively Confirmed Arterial Thrombosis | Up to approximately 4.5 years |
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed