Obinutuzumab in Primary FSGS
Primary Purpose
Primary Focal Segmental Glomerulosclerosis
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Obinutuzumab
Sponsored by
About this trial
This is an interventional treatment trial for Primary Focal Segmental Glomerulosclerosis
Eligibility Criteria
Inclusion Criteria:
- ≥ 18 years of age.
- Biopsy proven Focal Segmental Glomerulosclerosis (FSGS) lesion
- Foot process effacement ≥ 80% on electron microscopy.
- Presence of nephrotic syndrome (proteinuria > 3.5g/24hrs and serum albumin < 3.5 g/dl) prior to initiation of immunosuppressive therapy.
- Resistant or dependent on therapy, including corticosteroids or calcineurin inhibitors or who have failed rituximab. Patient who have contraindication to or refuse to take high dose corticosteroids are allowed.
Exclusion Criteria:
- Genetic or secondary forms of FSGS.
- Hepatitis B, C or HIV positive.
- Pregnant or breast-feeding.
- Active infection.
- Kidney transplant.
- Anemia with Hgb < 8.0 g/dL.
- Thrombocytopenia with platelet count < 100'000.
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complication.
- Patients who have received cyclophosphamide in the last 6 months.
- Patients who received rituximab previously with CD20 count of < 5 cells/microliter at the time of enrollment.
- For women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of less than (<) 1 percent (%) per year, during the treatment period and for at least 18 months after the last dose of study drug.
- For men: agreement to remain abstinent or use two adequate methods for contraception, including at least one method with failure rate of less than 1% per year during the treatment period and for at least 6 months (180 days) after the last dose of drug.
Sites / Locations
- Mayo Clinic in Rochester
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Primary Focal Segmental Glomerulosclerosis (FSGS)
Arm Description
Subjects with immunosuppression-dependent or immunosuppression/treatment-resistant primary FSGS or contraindication/patient refusal to take high dose corticosteroids, will receive obinutuzumab 1 gram on day 1 and 1 gram on day 15, given intravenously and then an identical course at 6 months.
Outcomes
Primary Outcome Measures
Change in proteinuria
Measured using 24 hour urine collection reported in mg/24h
Secondary Outcome Measures
Remission status at 6 months
The number of subjects to reach either complete remission or partial remission at 12 months after infusion. Complete remission defined as proteinuria < 0.3g/24 hrs. and no more than 20% decline in eGFR. Partial remission defined as 50% reduction in proteinuria and proteinuria < 3.5 g/24hrs and no more than 20% decline in eGFR.
Remission status at 12 months
The number of subjects to reach either complete remission or partial remission at 12 months after infusion. Complete remission defined as proteinuria < 0.3g/24 hrs. and no more than 20% decline in eGFR. Partial remission defined as 50% reduction in proteinuria and proteinuria < 3.5 g/24hrs and no more than 20% decline in eGFR.
Change in serum albumin
Blood serum collected and reported in g/dL
Serious Adverse Events (SAEs)
Number of subjects to experience serious adverse events including serious infection defined as severe UTI or pyelonephritis, pneumonias or other systemic infections requiring hospitalization
Proteinuria at 18 months
Measured using 24 hour urine collection reported in mg/24h
Proteinuria at 24 months
Measured using 24 hour urine collection reported in mg/24h
Full Information
NCT ID
NCT04983888
First Posted
July 21, 2021
Last Updated
June 13, 2023
Sponsor
Mayo Clinic
Collaborators
Genentech, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04983888
Brief Title
Obinutuzumab in Primary FSGS
Official Title
A Single-center, Phase 2 Open-label Trial Evaluating the Efficacy and Safety of OBINUTUZUMAB in Treatment of Immunosuppression-dependent or Immunosuppression/Treatment-resistant Primary FSGS, or Contraindication/Patient Refusal to Take High Dose Corticosteroids
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 17, 2021 (Actual)
Primary Completion Date
June 2025 (Anticipated)
Study Completion Date
September 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
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and efficacy of Obinutuzumab in inducing complete or partial remission of proteinuria.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Focal Segmental Glomerulosclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Primary Focal Segmental Glomerulosclerosis (FSGS)
Arm Type
Experimental
Arm Description
Subjects with immunosuppression-dependent or immunosuppression/treatment-resistant primary FSGS or contraindication/patient refusal to take high dose corticosteroids, will receive obinutuzumab 1 gram on day 1 and 1 gram on day 15, given intravenously and then an identical course at 6 months.
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab
Intervention Description
1g IV on day one and 1 g IV on day 15, followed by identical course at month 6
Primary Outcome Measure Information:
Title
Change in proteinuria
Description
Measured using 24 hour urine collection reported in mg/24h
Time Frame
Baseline, 6 months, 12 months
Secondary Outcome Measure Information:
Title
Remission status at 6 months
Description
The number of subjects to reach either complete remission or partial remission at 12 months after infusion. Complete remission defined as proteinuria < 0.3g/24 hrs. and no more than 20% decline in eGFR. Partial remission defined as 50% reduction in proteinuria and proteinuria < 3.5 g/24hrs and no more than 20% decline in eGFR.
Time Frame
6 months
Title
Remission status at 12 months
Description
The number of subjects to reach either complete remission or partial remission at 12 months after infusion. Complete remission defined as proteinuria < 0.3g/24 hrs. and no more than 20% decline in eGFR. Partial remission defined as 50% reduction in proteinuria and proteinuria < 3.5 g/24hrs and no more than 20% decline in eGFR.
Time Frame
12 months
Title
Change in serum albumin
Description
Blood serum collected and reported in g/dL
Time Frame
Baseline, 6 months, 12 months
Title
Serious Adverse Events (SAEs)
Description
Number of subjects to experience serious adverse events including serious infection defined as severe UTI or pyelonephritis, pneumonias or other systemic infections requiring hospitalization
Time Frame
24 months
Title
Proteinuria at 18 months
Description
Measured using 24 hour urine collection reported in mg/24h
Time Frame
18 months
Title
Proteinuria at 24 months
Description
Measured using 24 hour urine collection reported in mg/24h
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
≥ 18 years of age.
Biopsy proven Focal Segmental Glomerulosclerosis (FSGS) lesion
Foot process effacement ≥ 80% on electron microscopy.
Presence of nephrotic syndrome (proteinuria > 3.5g/24hrs and serum albumin < 3.5 g/dl) prior to initiation of immunosuppressive therapy.
Resistant or dependent on therapy, including corticosteroids or calcineurin inhibitors or who have failed rituximab. Patient who have contraindication to or refuse to take high dose corticosteroids are allowed.
Exclusion Criteria:
Genetic or secondary forms of FSGS.
Hepatitis B, C or HIV positive.
Pregnant or breast-feeding.
Active infection.
Kidney transplant.
Anemia with Hgb < 8.0 g/dL.
Thrombocytopenia with platelet count < 100'000.
Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complication.
Patients who have received cyclophosphamide in the last 6 months.
Patients who received rituximab previously with CD20 count of < 5 cells/microliter at the time of enrollment.
For women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of less than (<) 1 percent (%) per year, during the treatment period and for at least 18 months after the last dose of study drug.
For men: agreement to remain abstinent or use two adequate methods for contraception, including at least one method with failure rate of less than 1% per year during the treatment period and for at least 6 months (180 days) after the last dose of drug.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fernando Fervenza, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials
Learn more about this trial
Obinutuzumab in Primary FSGS
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