Evaluation of Glucocorticoids Plus Rituximab Compared to Glucocorticoids Plus Placebo for the Treatment of Patients With Newly-Diagnosed or Relapsing IgA Vasculitis (RIGA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospital Foch

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2024-11-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-516052-17-01

EudraCT number

2020-000729-13

ClinicalTrials.gov

NCT05329090

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To determine the efficacy of rituximab to induce remission in patients with newly-diagnosed or relapsing adult IgAV.

Secondary objectives 10

1. To determine the duration of efficacy of rituximab-based regimen to induce remission in patients with newly-diagnosed or relapsing adult IgAV
2. To assess the number of relapses
3. To compare the safety profile of rituximab-based regimen and glucocorticoids alone at days 180 and 360
4. To measure the glucocorticoids dose at days 180 and 360 and to compare the glucocorticoid sparing effect of rituximab
5. To assess the proportion of patients in complete or partial renal remission at days 180 and 360
6. To assess renal outcome
7. To compare sequelae assessed by the Vasculitis Damage Index at days 180 and 360 in both arms
8. To compare patient-reported outcomes (PRO) at days 180 and 360 after randomization in both arms, and during long-term follow-up
9. To compare functional disability and quality of life at days 180 and 360 after randomization in both arms
10. To compare the evolution of CD19+ cells in the two treatment groups, and to assess its correlation with clinical events during follow-up

Conditions and MedDRA coding

Patients with a diagnosis of IgAV according to Chapel Hill Consensus Conference definitions. Patients will require having a biopsy-proven diagnosis of IgAV.

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Biopsy-proven diagnosis of IgAV according to Chapel Hill Consensus Conference definitions
2. Patient aged of 18 years or older
3. Patients with newly-diagnosed disease or relapsing disease at the time of screening, with an active disease defined by active manifestations attributable to IgAV
4. Patients with severe involvement of at least one organ
5. Patients within the first 21 days following initiation/increase of corticosteroids at a dose ≤1 mg/kg/day (pulses of methylprednisolone before oral corticosteroids therapy are not mandatory by the protocol but are allowed according to the physician’s discretion )
6. Patients must have signed an informed consent form prior to any study related procedures
7. Patients must be affiliated to the national health insurance

Exclusion criteria 19

1. Patients with ANCA-associated vasculitis, or other vasculitis, defined by the ACR criteria and/or the Chapel Hill Consensus Conference
2. Patients with hypersensitivity to human or chimeric monoclonal antibodies
3. Patients with contraindication to use rituximab
4. Patients treated with any concomitant drugs contraindicated for use with the rituximab according to its SmPC
5. Patients with contraindication to use routine care treatments (Glucocorticoids, Angiotensin-converting-enzyme (ACEis) or angiotensin receptor blockers (ARBs), dexchlorphéniramine)
6. Patients in a severely immunocompromised state
7. Patients with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric disorders, that could interfere with his/her compliance to the protocol requirements
8. Patients currently participating in another clinical study or 3 months prior to randomization
9. Patients suspected not to be observant to the proposed treatments
10. Patients with IgAV in remission of the disease
11. Patients with severe cardiac failure defined as class IV in New York Heart Association
12. Patients with severe, uncontrolled cardiac disease
13. Patients with acute infections or chronic active infections (including HIV, HBV or HCV)
14. Patients with active cancer or recent malignancy (<5 years), except basocellular carcinoma and prostatic cancer of low activity controlled by hormonal treatment
15. Pregnant women and breastfeeding. Patients with childbearing potential must use reliable contraceptive methods throughout the study and at least for 12 months after the last study drug administration
16. Patients with IgAV who have already been treated with rituximab within the previous 12 months
17. New onset of immunosuppressive therapy within the last 3 months
18. Patients unable to give written informed consent prior to participation in the study,
19. Being deprived of liberty or under guardianship.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The proportion of patients alive who achieve remission with a prednisone dose of 0 mg/day at both days 180 and 360.
2. The primary assessment criterion of this trial is the proportion of patients alive who achieved remission with a prednisone dose of 0 mg/day at both days 180 and 360.

Secondary endpoints 18

1. Proportion of patients in remission at days 180
2. Proportion of patients in remission at days 360
3. Proportion of patients in remission both at days 180 and 360
4. Proportion of patients achieving remission for ≥3 consecutive months over the 360 days study period
5. Proportion of patients with BVAS=0 (or BVAS of ≤5 if all scores were due to persistent hematuria or proteinuria) and a prednisone dose ≤5 mg/day at days 180 and 360
6. Mean total accrued duration in weeks in remission of the disease (as previously defined) over the 360 days study period
7. Proportion of patients in complete renal and partial renal remission at days 180 and 360
8. Renal parameters at days 180 and 360 compared with baseline: eGFR, daily proteinuria, hematuria, arterial hypertension, use of angiotensin converting enzyme inhibitor, occurrence of end-stage renal disease
9. Prednisone dosage at days 180 and 360 in the two treatment groups
10. Area under the curve for prednisone dose at days 180 and 360 in the two treatment groups
11. Number of major and minor relapse at 12 months
12. Cumulative incidence of relapse at 12 months
13. Time to first IgAV relapse
14. Adverse events, expressed as adverse events according to the CTCAE toxicity grading system per patient-year at days 180 and 360 for the following adverse events combined: death (all causes), grade 2 or higher leukopenia or thrombocytopenia, grade 3 or higher infections, 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)
15. The Vasculitis Damage Index at days 180 and 360 in the two treatment groups
16. Quality of life as measured by the HAQ and SF-36 questionnaires at days 180 and 360
17. The patient-reported outcomes (PRO) including patient-reported disease activity, anxiety and depression, burden of the disease and treatment and adherence to treatment, at days 180 and 360 after randomization in the two treatment groups, and during the long-term follow-up
18. Patient survival

Investigational products

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

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospital Foch

Sponsor organisation

Hospital Foch

Address

40 Rue Worth

City

Suresnes

Postcode

92150

Country

France

Scientific contact point

Organisation

Hospital Foch

Contact name

Marjolaine NGOLLO

Public contact point

Organisation

Hospital Foch

Contact name

Marjolaine NGOLLO

Locations

1 EU/EEA country · 42 investigational sites

By country

Investigational sites

Results and documents

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

Documents 6 files

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

Application history

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