PR3-AAV Resilient Remission or PRRR

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Brief Title

PR3-AAV Resilient Remission or PRRR

Official Title

A Randomized, Double-Blind, Active Comparator-Controlled Study to Evaluate the Effect of Obinutuzumab Versus Rituximab in PR3-Patients With Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis

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).
    


Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Number of patients to achieve both complete remission and seronegativity for ANCA.

Secondary Outcome

 Number of patients to achieve sustained complete remission 6 months

Condition

Granulomatosis With Polyangiitis

Intervention

Obinutuzumab

Study Arms / Comparison Groups

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

30

Start Date

July 2022

Completion Date

July 2024

Primary Completion Date

January 2024

Eligibility Criteria

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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.

          -  Diagnosis of human anti-chimeric antibodies (HACA) formation.

          -  Subjects who are premenopausal and are:

               -  Pregnant on the basis of a serum pregnancy test,

               -  Breastfeeding, or

               -  Do not agree to use effective method(s) of contraception

          -  Use of prohibited medications: They have used any of the prohibited medication listed
             in Section 5.9.1.

          -  Plasma exchange: They have been treated with plasma exchange within the 3 months
             preceding the screening visit.

          -  History of intolerance to rituximab or other chimeric monoclonal antibodies (e.g.,
             infliximab).

          -  Recent vaccination: They have had a live vaccine fewer than 4 weeks (28 days) before
             or during randomization (vaccination with live vaccine through the end of study
             participation is contraindicated).

          -  Daily use of non-steroidal anti-inflammatory drugs (NSAIDs)

          -  Exclusion criteria related to laboratory parameters:

               -  Bone marrow suppression as evidenced by a total white count < 4 x10 /l,
                  hemoglobin < 7 gm/dl or platelet count < 100,000/μl

               -  Aspartate aminotransferase or alanine aminotransferase or amylase > 2.5 times the
                  upper limit of normal, unless attributed to vasculitis
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Ulrich Specks, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT05376319

Organization ID

21-012197


Responsible Party

Principal Investigator

Study Sponsor

Mayo Clinic


Study Sponsor

Ulrich Specks, MD, Principal Investigator, Mayo Clinic


Verification Date

May 2022