OBI-WAN : Obinutuzumab for remission induction in patients with relapsing PR3-ANCA granulomatosis with polyangiitis (Wegener’s). Phase 2 prospective, open-label study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

19 Dec 2025 → ongoing

Decision date (initial)

2025-03-27

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Direction Générale de l’Offre des Soins du Ministère de la santé et de la prévention, PHRC-N 2020

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To determine the efficacy of obinutuzumab in patients with relapsing PR3-ANCA positive patients at week 24 (month 6), defined by:
1) the percentage of patients who achieved a BVAS of 0,
2) a negativation of PR3-ANCA, and
3) successful discontinuation of corticoids treatment after completion of the prednisone taper.

Secondary objectives 7

1. To determine the safety of obinutuzumab by analyzing the proportion of participants experiencing adverse events and severe adverse events
2. To determine the rate of mortality
3. To determine the rate of disease flares, including minor and major relapses
4. To determine the rate of BVAS of 0 during treatment with prednisone at a dose of less than 10 mg per day at 6 months
5. To determine the duration of B-cell depletion after obinutuzumab
6. To evaluate the impact on the quality of life and other patient-reported outcomes (PRO) of obinutuzumab at week 24 and 52
7. To determine sequelae assessed by the Vasculitis Damage Index at week 24 and 52

Conditions and MedDRA coding

PR3-ANCA granulomatosis with polyangiitis (Wegener’s)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patient aged of 18 years or older
2. Patients with relapsing granulomatosis with polyangiitis positive for PR3-ANCA at inclusion, according to the ACR/EULAR 2022 classification criteria, and/or the 2012 revised Chapel Hill Consensus Conference definition.
3. Patients with an active disease defined as a Birmingham Vasculitis Activity Score (BVAS) ≥ 3
4. Patients within the first 21 days following initiation/increase of glucocorticoids at a dose ≤1 mg/kg/day
5. Patient able to give written informed consent prior to participation in the study
6. Affiliation with a mode of social security (profit or being entitled)

Exclusion criteria 21

1. Patients with MPO-positive AAV, or other vasculitis, defined by the ACR criteria and/or the Chapel Hill Consensus Conference,
2. Patients with hypersensitivity to obinutuzumab or to its excipients,
3. Contra-indications to auxiliary medicinal products (methylprednisolone, paracetamol, prednisone, dexchlorpheniramine),
4. Patients with other uncontrolled diseases that could interfere with participation in the trial according to the protocol,
5. Patients suspected not to be observant to the proposed treatments,
6. Pregnant women and lactation,
7. Men who refuse to use effective method of contraception (condom) from the date of consent through the end of the study and at least 18 months after stopping obinutuzumab,
8. Patient participating in another investigational therapeutic study,
9. Protected adults (including individual under legal guardianship by court order or curatorship) or adults deprived of liberty,
10. Patients unable to give written informed consent prior to participation in the study.
11. Patients with vasculitis in remission of the disease defined as a BVAS < 3,
12. Patients with a newly-diagnosis of GPA
13. Patients treated with rituximab within the last 6 months before inclusion,
14. Patients treated with cyclophosphamide within the last 6 months before inclusion,
15. Patients with severe cardiac failure defined as class IV in New York Heart Association
16. Subject known to be seropositive for human immunodeficiency virus (HIV), hepatitis B (included history of previous infection) or hepatitis C,
17. Patients with active cancer or recent cancer (< 5 years), except basocellular carcinoma and prostatic cancer of low activity controlled by hormonal treatment,
18. Patients with hypersensitivity to a monoclonal antibody or biologic agent,
19. Patients with severe liver insufficiency (prothrombin time <50% and total bilirubin >50 micrmol/L) or pulmonary insufficiency requiring nasal oxygen
20. Patients with an active infection or a history of chronic or recurrent infections
21. Vaccination with live virus vaccines in the 4 weeks before study enrolment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The percentage of patients who achieved clinical and serological remission at week 24 (month 6), defined by: 1) a BVAS of 0; 2) a negativation of PR3-ANCA; 3) a successful completion of the prednisone taper

Secondary endpoints 7

1. The number of adverse events, expressed as adverse events according to the CTCAE toxicity grading system per patient-year at week 24 and 52 for the following adverse events combined: death (all causes), grade 2 or higher leukopenia or thrombocytopenia, grade 3 or higher infections, hemorrhagic cystitis, malignancies, venous thromboembolic events, hospitalization resulting either from the disease or from a complication due to the study treatment, infusion reactions (within 24 hours of infusion
2. Number and causes of deaths over the 12 months study period
3. Proportion of participants who had vasculitis relapses (BVAS > 0), including minor and major relapses over the 12 months study period
4. Proportion of participants who remain with a BVAS of 0 during the treatment period with prednisone at a dose of less than 10 mg per day
5. The time to B-cell repopulation defined by detectable CD19+ B cells in peripheral blood over the 12 months study period
6. The patient-reported outcomes (PRO) including HAQ and SF-36, patient-reported disease activity, anxiety and depression, burden of the disease and treatment and adherence to treatment, at week 24 and 52
7. The Vasculitis Damage Index at week 24 and 52

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Benjamin TERRIER, Coordinating investigator

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Benjamin TERRIER, Coordinating investigator

Locations

1 EU/EEA country · 28 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications