A Study to Evaluate Crovalimab in People With Antiphospholipid Syndrome (APS)

A Phase II, Randomized, Double-blind, Placebo-controlled, Multicenter Study Evaluating Efficacy, Safety, and Pharmacokinetics of Crovalimab in Patients With Antiphospholipid Syndrome (APS)

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.

Study Overview

• Status: Withdrawn
• Conditions: Antiphospholipid Syndrome
• Intervention / Treatment: Drug: Crovalimab; Drug: VKA; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Crovalimab + 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.	Drug: Crovalimab; 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.; Other Names: RO7112689; SKY59; PIASKY; Drug: VKA; 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).
Placebo Comparator: Placebo + 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.	Drug: VKA; 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).; Drug: Placebo; Placebo matching crovalimab will be administered as per the schedule specified in the respective arm.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Estimated): March 16, 2026
• Primary Completion (Estimated): March 11, 2030
• Study Completion (Estimated): December 2, 2030

Study Registration Dates

• First Submitted: September 11, 2025
• First Submitted That Met QC Criteria: September 11, 2025
• First Posted (Actual): September 15, 2025

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Autoimmune Diseases; Immune System Diseases; Antiphospholipid Syndrome; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: BO46107; 2025-522980-14-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No