NCT07268521: CRYOBI

A Multicenter Phase 2 Single-arm Proof-of-concept Trial Assessing the Efficacy and Safety of Obinutuzumab in the Treatment of Non-infectious Active Cryoglobulinemia Vasculitis Refractory or Intolerant to Rituximab

Not yet recruiting Phase 2 Last updated 5 December 2025

What this trial tests

Phase 2 trial testing Obinutuzumab in Cryoglobulinemic Vasculitis (CV) in 30 participants. Not yet recruiting.

Timeline

1 December 2025

Primary endpoint
1 April 2028

1 September 2028

Quick facts

Lead sponsor	Assistance Publique - Hôpitaux de Paris
Phase	Phase 2
Status	Not yet recruiting
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	30
Start date	1 December 2025
Primary completion	1 April 2028
Estimated completion	1 September 2028

Drugs / interventions tested

• Obinutuzumab — full drug profile →

Conditions studied

• Cryoglobulinemic Vasculitis (CV) — all drugs for Cryoglobulinemic Vasculitis (CV) →

Sponsor

Assistance Publique - Hôpitaux de Paris — full company profile →

Who can join

18 and older, any sex, with Cryoglobulinemic Vasculitis (CV). Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Cryoglobulinemic vasculitis (CV) is a rare life threatening systemic immune-complex-mediated vasculitic syndrome. Symptoms range from arthralgia, purpura to more severe manifestations such as peripheral neuropathy, glomerulonephritis, and skin necrosis.1 CV is associated with significant morbidity and mortality. The management of non-infectious mixed CV is currently based on steroids, and anti-CD20 monoclonal antibody Rituximab (RTX). Infectious complications of immunosuppressants (IS) remain the main cause of death in CV. During the last decade, studies reported efficacy of RTX in patients with CV in 65-70% of patients as compared to 30% for other IS (azathioprine…). However, CV relapse is noted in up to 40% patients within few days to 19 months after the last RTX infusion2. Following RTX, serum levels of B lymphocyte stimulator (BLyS) significantly increased and may favour the survival of autoreactive B cell clones and relapses of CV. A recent study has shown that RTX does not reset defective early B cell tolerance checkpoints. Incomplete B cell depletion following treatment with RTX may be associated with poor clinical response.

Moreover, some patients develop a serum sickness reaction to RTX that contraindicate further use of the medication2. Thus, there are important therapeutic unmet needs in CV patients that are refractory or intolerant to RTX.

Obinutuzumab (OBZ) is a type II anti-CD20 monoclonal antibody with a glycomodified Fc, approved in 2013 for the treatment of chronic lymphocytic leukemia. Reddy et al. found that OBZ was at least 2-fold more efficient than RTX at inducing B-cell cytotoxicity in in vitro whole blood assays of patients with rheumatoid arthritis and systemic lupus erythematosus. In lupus nephritis, OBZ resulted in increased complete and partial renal responses compared with placebo when added to mycophenolate mofetil and steroids for the treatment of lupus nephritis. There is a strong rationale for using OBZ in CV. OBZ is currently used off label in CV patients intolerant to RTX and case reports pointed out its effectiveness in CV4.5. CRYOBI is the first prospective multicenter phase 2 proof-of-concept trial assessing efficacy of OBZ in CV refractory or intolerant to RTX.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.