PR3-AAV Resilient Remission or PRRR

NCT05376319 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 21-012197
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of obinutuzumab for the treatment of proteinase 3 Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis (PR3-AAV).

Conditions

Granulomatosis With Polyangiitis; Microscopic Polyangiitis; ANCA Associated Vasculitis

Keywords

Granulomatosis with Polyangiitis; Microscopic Polyangiitis; PR3-ANCA; ANCA-associated Vasculitis

Outcome Measures

Primary Outcomes (1)

• Number of Patients to Achieve Both Complete Remission and Seronegativity for ANCA.

  Complete remission is defined as a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) of 0 without glucocorticoids beyond the prescribed prednisone taper. Seronegativity for ANCA is defined as a negative test for antibodies directed against serine proteinase 3 (i.e., a negative PR3-ANCA assay).

  6 months

Secondary Outcomes (3)

• Number of Patients to Achieve Sustained Complete Remission 6 Months

  6 months

• Number of Patients to Achieve Sustained Complete Remission 12 Months

  12 months

• Number of Patients to Achieve Sustained Complete Remission 18 Months

  18 months

Study Arms (2)

Intravenous dose of obinutuzumab

EXPERIMENTAL

Subjects who have clinical diagnoses of either granulomatosis with polyangiitis or microscopic polyangiitis will receive two intravenous doses of obinutuzumab

Drug: Obinutuzumab

Intravenous dose of rituximab

ACTIVE COMPARATOR

Subjects who have clinical diagnoses of either granulomatosis with polyangiitis or microscopic polyangiitis will receive two intravenous doses of rituximab

Drug: Rituximab

Interventions

Obinutuzumab DRUG

1000 mg per infusion given approximately two weeks apart, on day 1 and on day 15

Intravenous dose of obinutuzumab

Rituximab DRUG

1000 mg per infusion given approximately two weeks apart, on day 1 and on day 15

Intravenous dose of rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fulfillment of the definitions of the Second Chapel Hill Consensus Conference for ANCA-associated vasculitis (either granulomatosis with polyangiitis or microscopic polyangiitis).
• Positivity for ANCA, directed against proteinase-3 (PR3)
• Severe newly-diagnosed disease or severe relapsing disease. Severe relapsing disease is defined as at least one major BVAS/WG item or a score ≥ 3 and the investigator deems standard treatment for severe disease is necessary.
• Minimum BVAS/WG of 3
• Relapsing patients must have B cells detectable in the peripheral blood.
• Patients must have completed COVID19 vaccination (including booster if eligible) at least 4 weeks prior to enrollment with a positive spike protein antibody test result. Patients who have recovered from COVID19 prior to screening with a positive spike protein antibody test result but have not been vaccinated are also eligible.
• Female subjects of childbearing potential who are not sterile must agree to use an acceptable method of contraception for 18 months after the last dose of infusion medication. Male subjects who are not sterile whose female partners are of childbearing potential must agree to use an acceptable method of contraception for 180 days after the last dose of infusion medication.
• Females of childbearing potential include any female who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (to be considered postmenopausal, the patient must have had amenorrhea for \>12 consecutive months).
• Acceptable methods of contraception include the use of at least two of the following: 1) intrauterine device; 2) hormonal contraceptives for at least 30 days prior to first dose infusion (oral, injectable, implant or ring); 3) barrier contraceptives (condom or diaphragm) with spermicide; or 4) abstinence.

You may not qualify if:

• Diagnosis with eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome) as defined by the Chapel Hill Consensus Conference.
• Positive serum assays for ANCA directed against myeloperoxidase (MPO-ANCA)
• Non-severe AAV, defined as disease that does not justify treatment with both B cell depletion and a four-month glucocorticoid taper.
• Any of the co-morbidities:
• Allergies: a history of severe allergic reactions to human or chimeric monoclonal antibodies or murine protein.
• Infection (systemic): an active systemic infection at screening visit
• Infection (deep space): have been diagnosed as having a deep-space infection, such as osteomyelitis, septic arthritis, or pneumonia complicated by empyema or lung abscesses, within 6 months prior to the screening visit
• Infection (blood borne): active hepatitis B or active hepatitis C or a documented history of HIV, hepatitis B, or hepatitis C
• Infection (history): History of recurrent significant infection or history of recurrent bacterial infections
• Liver disease: acute or chronic liver disease that is deemed sufficiently severe to impair their ability to participate in the trial.
• Renal disease: a history of documented anti-glomerular basement membrane disease (anti-GBM disease).
• Malignancy: Active or history of malignancy in the last 5 years. Individuals with squamous cell or basal cell skin carcinomas and individuals with cervical carcinoma in situ may be enrolled if they have received curative surgical treatment.
• Active COVID-19 infection.
• Uncontrolled disease: evidence of glucocorticoid dependent disease (such as asthma, COPD, psoriasis or IBD, etc.) requiring consistently greater than 10 mg of prednisone for disease control which might affect endpoint assessment or,
• Other uncontrolled diseases, including any uncontrolled psychiatric disorders, drug and alcohol abuse, that could interfere with participation in the trial according to the protocol.

Sponsors & Collaborators

• Mayo Clinic: lead
• Genentech, Inc.: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Interventions

obinutuzumab; Rituximab

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Study was discontinued early due to funding termination by industry sponsor.

Results Point of Contact

• Title: Ulrich Specks, M.D.
• Organization: Mayo Clinic

specks.ulrich@mayo.edu

507-284-2494

Study Officials

• Ulrich Specks, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 11, 2022
• First Posted: May 17, 2022
• Study Start: June 30, 2023
• Primary Completion: May 7, 2024
• Study Completion: May 7, 2024
• Last Updated: May 6, 2026
• Results First Posted: July 31, 2024

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)