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PR3-AAV Resilient Remission or PRRR

Primary Purpose

Granulomatosis With Polyangiitis, Microscopic Polyangiitis, ANCA Associated Vasculitis

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Obinutuzumab
Rituximab
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Granulomatosis With Polyangiitis focused on measuring Granulomatosis with Polyangiitis, Microscopic Polyangiitis, PR3-ANCA, ANCA-associated Vasculitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital
  • Mayo Clinic RochesterRecruiting
  • University of PennsylvaniaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Intravenous dose of obinutuzumab

Intravenous dose of rituximab

Arm Description

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

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Number of patients to achieve sustained complete remission 6 months
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.
Number of patients to achieve sustained complete remission 12 months
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.
Number of patients to achieve sustained complete remission 18 months
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.

Full Information

First Posted
May 11, 2022
Last Updated
October 18, 2023
Sponsor
Mayo Clinic
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05376319
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 30, 2023 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
July 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
Genentech, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Granulomatosis With Polyangiitis, Microscopic Polyangiitis, ANCA Associated Vasculitis
Keywords
Granulomatosis with Polyangiitis, Microscopic Polyangiitis, PR3-ANCA, ANCA-associated Vasculitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intravenous dose of obinutuzumab
Arm Type
Experimental
Arm Description
Subjects who have clinical diagnoses of either granulomatosis with polyangiitis or microscopic polyangiitis will receive two intravenous doses of obinutuzumab
Arm Title
Intravenous dose of rituximab
Arm Type
Active Comparator
Arm Description
Subjects who have clinical diagnoses of either granulomatosis with polyangiitis or microscopic polyangiitis will receive two intravenous doses of rituximab
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab
Intervention Description
1000 mg per infusion given approximately two weeks apart, on day 1 and on day 15
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
1000 mg per infusion given approximately two weeks apart, on day 1 and on day 15
Primary Outcome Measure Information:
Title
Number of patients to achieve both complete remission and seronegativity for ANCA.
Description
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).
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Number of patients to achieve sustained complete remission 6 months
Description
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.
Time Frame
6 months
Title
Number of patients to achieve sustained complete remission 12 months
Description
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.
Time Frame
12 months
Title
Number of patients to achieve sustained complete remission 18 months
Description
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.
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ulrich Specks, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Colebrooke Johnson
Phone
617-643-9627
Email
cjohnson110@mgh.harvard.edu
First Name & Middle Initial & Last Name & Degree
John Stone, MD, MPH
Facility Name
Mayo Clinic Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael C. Stachowitz
Phone
507-284-4862
Email
stachowitz.michael@mayo.edu
First Name & Middle Initial & Last Name & Degree
Ulrich Specks, MD
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alison Keenan
Phone
215-614-4406
Email
rheumatologyresearch@uphs.upenn.edu
First Name & Middle Initial & Last Name & Degree
Peter Merkel, MD

12. IPD Sharing Statement

Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

Learn more about this trial

PR3-AAV Resilient Remission or PRRR

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