Discontinuation of rituximab compared with rituximab maintenance in ANCA-associated vasculitis – a randomized non-blinded controlled trial (DISRITUX)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Oestergoetland

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

12 Dec 2024 → ongoing

Decision date (initial)

2024-06-20

Transition trial

No

Low-intervention

Yes

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy

The primary objective is to study the relapse rate after discontinuation of rituximab compared with rituximab maintenance in ANCA-associated vasculitis (AAV) patients in stable remission

Secondary objectives 6

1. Monitor and investigate relapses (both minor and major) according to rate, time, and proportions
2. Evaluate whether the burden of treatment related side effects, including infections, is reduced in the discontinuation arm as compared with the treatment maintenance arm
3. Evaluate adverse event rates
4. Evaluate if quality of life (QOL) is improved in the discontinuation arm compared to the continuation group
5. Explore and identify more reliable and predictive biomarkers for relapse risk in AAV patients in stable remission (no disease activity for the last 6 months)
6. Investigate health economics by comparing previously used and validated QOL measures (RAND-36, EQ-5D, HADS, AAV-PRO) in AAV RCTs during the study in the two groups as well as Quality-adjusted Life Years QALY by assessing treatment costs and complications/AEs

Conditions and MedDRA coding

ANCA-associated vasculitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Informed consent given by patient according to national regulations
2. AAV [granulomatosis with polyangiitis or microscopic polyangiitis], according to the definitions of the Chapel Hill Consensus Conference
3. Current or history of PR3/MPO-ANCA positivity by ELISA
4. A stable remission (BVAS =0) for the last 24 months
5. Has received a minimum of 24 months of RTX maintenance therapy and last dose minimum 6 months prior to screening. A Rituximab dose of 500 mg or 1000 mg 6 months before inclusion will be accepted
6. Females of childbearing potential must agree to avoid pregnancy during treatment with RTX during 12 months after discontinuation of RTX. They also must have a negative urine or serum pregnancy test at the screening visit. Adequate contraception methods must be followed according to clinical routine for these patients

Exclusion criteria 14

1. Significantly abnormal eGFR at screening (≤15 eGFR ml/min/1.73m2)
2. Previous therapy with any of the following: - any biological B cell depleting agent other than rituximab during the last 6 months (i.e Obinutuzumab, Belimumab) - IVIg, infliximab, etanercept, adalimumab, abatacept or plasma exchange in past 3 months - any investigational agent within 28 days of screening, or 5 half-lives of the investigational drug (whichever is longer)
3. Ongoing therapy with any of the following. - disease modifying therapy related for AAV such as methotrexate, azathioprine, and mycophenolate mofetil or glucocorticoid >5 mg daily
4. Recurrent AAV relapses less than 6 months off immunosuppressive medication
5. Significant or uncontrolled medical disease not related to AAV, which in the investigator’s opinion would preclude patient participation
6. Presence of another multisystem autoimmune disease, including Churg Strauss syndrome, systemic lupus erythematosus, anti-GBM disease, or cryoglobulinaemic vasculitis
7. History of severe allergic or anaphylactic reactions to humanized or murine chimeric monoclonal antibodies
8. Past or current history of hepatitis B virus, current active hepatitis C
9. Bone marrow suppression as evidenced by a total white count < 3.0 x109/l and/or neutropenia neutrophil count < 1.5 × 109
10. Hypogammaglobulinemia, IgG <3 g/L
11. History of malignancy within the past five years or any evidence of persistent malignancy. Fully excised basal cell or squamous cell carcinomas of the skin, or cervical carcinoma in situ which has been treated or excised in a curative procedure is allowed
12. Females who are lactating or pregnant at screening (verified with a negative urine or serum pregnancy test at screening visit).
13. Medical, psychiatric, cognitive, or other conditions that, in the investigator's opinion, compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study
14. Participant in another clinical trial with therapeutic intervention or use of any other investigational agent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease relapse rate, from randomization to relapse

Secondary endpoints 13

1. Time to relapse (either minor or major)
2. Proportion of patients who maintain AAV remission at 24 and 36 months.
3. Serological response during study (ANCA positivity vs negativity)
4. Loss of kidney function (eGFR slope from randomization+ fixed points at 12, 24, and 36 months)
5. Start of kidney replacement therapy
6. Duration (number of months) and doses of RTX treatment prior to randomization
7. Duration (number of months) of GC exposure prior to randomization
8. Cumulative GC exposure from randomization to end of study end of study or relapse whichever comes first
9. Cumulative accrual of damage measured by the Vasculitis Damage Index (VDI) scale
10. Health-related quality of life measurements
11. Serious adverse event rate
12. Frequency of AEs of special interest (AESI)
13. Health economics

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Oestergoetland

Sponsor organisation

Region Oestergoetland

Address

Universitetssjukhuset 1

City

Linkoping

Postcode

581 85

Country

Sweden

Scientific contact point

Organisation

Region Oestergoetland

Contact name

Coordinating principle investigator

Public contact point

Organisation

Region Oestergoetland

Contact name

Project coordinator

Third parties 1

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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