Comparative and Efficacy Study of ACTHar Gel Alone or in Combination With Tacrolimus in Fibrillary Glomerulopathy (FACT)
Primary Purpose
Renal Disease
Status
Withdrawn
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Acthar 80 UNT/ML Injectable Solution
Oral Tab Tacrolimus
Sponsored by
About this trial
This is an interventional treatment trial for Renal Disease
Eligibility Criteria
Histologic Inclusion Criteria:
All patients with a diagnosis of The Fibrillary GN wbe classified according to the Nasr nomenclature:
- Renal biopsy demonstrating JB9 Positive staining within 3 years of study randomization
- Mesangial expansion with/without glomerular sclerosis diffuse sclerosis
4) Crescents or capillary proliferation Note: Patients with > 50% interstitial fibrosis will not be eligible for study
Inclusion Criteria:
- Female ag
- Biopsy proven Fibrillary GN within 3 years of study randomization
- Stable Maximum RAAS inhibition X 40 weeks prior to randomization Note: Maximum inhibition will be the discretion of the site PI
- eGFR > 25 mls/min
- UP/Cr ratio > 2000 mg/gm 5 Note: IF UP/Cr less than 2000 mg/gm, a formal urine collection for total protein can be performed. The total 24-hour will need to >/= 2000mg.
- Blood pressure targeted to < 140 at the time of randomization
- Patients with MGUS without history of myeloma WILL be eligible.
- Patients with monoclonal staining for fibrillary fibers will be excluded
- Patients with Type II non-insulin dependent diabetes WILL be eligible provided the renal biopsy does not show nodular Kimmelstiel Wilson lesions
Exclusion
- Patients with MGUS and history of myeloma WILL be eligible
- Patients with active viral production of either B or C as evidence by historical PCR test positive for active viral shedding
- HIV seropositivity
- Renal biopsy data with > 5Interstitialxxxx Fibrosis
- Patient with active or a known history
- Patients with insulin Dependent diabetes mellitus will be excluded Note: Patients diabetes and are well controlled without the need for insulin WILL be eligible for the study.
- Patients with Type non-insulin diabetes WILL be eligible provided the renal biopsy does not s nodular Kimmelstiel Wilson lesions.
- Patients receiving steroids, MMF, cyc, Azathioprine or other immunosuppressive agent with of study random Note: Wash medications will be allowed at the screening visit
- Patients having received Rituximab or cell modifying biologic bbtherapy within 60 months of randomiza
Sites / Locations
- Georgia Nephrology Research Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
ACTHar gel combined with Tacrolimus
ACTHar gel
Arm Description
ACTHar Gel units 2 times per week plus oral Tacrolimus (1.0 mg BID) titrating to a trough level of 4-6 ng/ml for 52 weeks
ACTHar Gel units 2 times per week for 52 weeks
Outcomes
Primary Outcome Measures
change in UP/Cr ratio in patients with biopsy proven Fibrillary after treated with ACTHar gel alone OR in combination with oral Tacrolimus
The change in UP/Cr ratio in patients with biopsy proven Fibrillary after 12 months of treatment with ACTHar gel (80 units SQ 2X/week) alone OR in combination with oral Tacrolimus (1.0 mg PO BID). The change in UP/Cr for each group will also be compared to baseline UP/Cr ratios prior to randomization
Secondary Outcome Measures
relative change in UP/Cr
The relative change in UP/Cr at 24 months (12 months after stopping both ACTH and Tacrolimus) in the ACTHar gel group and the ACTHar gel + Tacrolimus group.
T that achieves complete, partial or clinical responses
The percentage of patients in the ACTHar gel alone ACTHar gel + Tacrolimus group that achieves complete, partial or clinical responses after 12 months of therapy
Full Information
NCT ID
NCT04080076
First Posted
June 28, 2019
Last Updated
September 20, 2022
Sponsor
NephroNet, Inc.
Collaborators
Mallinckrodt
1. Study Identification
Unique Protocol Identification Number
NCT04080076
Brief Title
Comparative and Efficacy Study of ACTHar Gel Alone or in Combination With Tacrolimus in Fibrillary Glomerulopathy
Acronym
FACT
Official Title
A Multicenter Comparative and Efficacy Study of ACTHar Gel Alone or in Combination With Tacrolimus in Fibrillary Glomerulopathy
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Withdrawn
Why Stopped
Study was updated and issued a new NCT number.
Study Start Date
January 12, 2019 (Actual)
Primary Completion Date
September 6, 2024 (Anticipated)
Study Completion Date
September 6, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NephroNet, Inc.
Collaborators
Mallinckrodt
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
No
5. Study Description
Brief Summary
Treatment with combination ACTHar gel and Tacrolimus therapy or ACTHar gel therapy alone in lowering urinary protein to creatinine (UP/Cr) ratios
Detailed Description
This is a multicenter, Phase 4, prospective, open labeled study to compare the safety, tolerability, and efficacy of a 12month course of ACTHar Gel and Tacrolimus therapy or ACTHar gel therapy alone in lowering urinary protein to creatinine (UP/Cr) ratios.
The addition of tacrolimus patients exhiba partial to ACTH resulted in a further reduction in Fibrillary.
Spe #1-will randomize with biopsy proven DNA-JB9 positive Fibrillary glomerulopathy to receive course of ACTHar gel alone at 80 units per week or in combination with oral Tacrolimus at 1 mg BID
Hypothesis Treatment with ACTHar Gel with oral Tacrolimus will result in a higher eGFR after 24 months of follow up than patients randomized to ACTHar gel therapy alone.
Hy3: Combination therapy of ACTHar Gel and Tacrolimus in patients with DNA-JB9 positive Fibrillary will lead to significant markers of podocyte injury compared ACTHar Gel alone.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
ACTHar gel alone- patients will receive 80units SQ 2X/week for 52 weeks
ACTH gel 80 units 2X per week plus oral Tacrolimus (1.0 mg BID) titrating to a trough level of 4-6 ng/ml for 52 weeks
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ACTHar gel combined with Tacrolimus
Arm Type
Active Comparator
Arm Description
ACTHar Gel units 2 times per week plus oral Tacrolimus (1.0 mg BID) titrating to a trough level of 4-6 ng/ml for 52 weeks
Arm Title
ACTHar gel
Arm Type
Active Comparator
Arm Description
ACTHar Gel units 2 times per week for 52 weeks
Intervention Type
Drug
Intervention Name(s)
Acthar 80 UNT/ML Injectable Solution
Intervention Description
ACTHar 80 Units SQ 1042 x Week
Intervention Type
Drug
Intervention Name(s)
Oral Tab Tacrolimus
Intervention Description
Oral Tab Tacrolimus (1.0 mg PO BID) in combination with ACTHar 80 Units SQ 2 X week
Primary Outcome Measure Information:
Title
change in UP/Cr ratio in patients with biopsy proven Fibrillary after treated with ACTHar gel alone OR in combination with oral Tacrolimus
Description
The change in UP/Cr ratio in patients with biopsy proven Fibrillary after 12 months of treatment with ACTHar gel (80 units SQ 2X/week) alone OR in combination with oral Tacrolimus (1.0 mg PO BID). The change in UP/Cr for each group will also be compared to baseline UP/Cr ratios prior to randomization
Time Frame
12 months
Secondary Outcome Measure Information:
Title
relative change in UP/Cr
Description
The relative change in UP/Cr at 24 months (12 months after stopping both ACTH and Tacrolimus) in the ACTHar gel group and the ACTHar gel + Tacrolimus group.
Time Frame
24 months
Title
T that achieves complete, partial or clinical responses
Description
The percentage of patients in the ACTHar gel alone ACTHar gel + Tacrolimus group that achieves complete, partial or clinical responses after 12 months of therapy
Time Frame
12 months
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Histologic Inclusion Criteria:
All patients with a diagnosis of The Fibrillary GN wbe classified according to the Nasr nomenclature:
Renal biopsy demonstrating JB9 Positive staining within 3 years of study randomization
Mesangial expansion with/without glomerular sclerosis diffuse sclerosis
4) Crescents or capillary proliferation Note: Patients with > 50% interstitial fibrosis will not be eligible for study
Inclusion Criteria:
Female ag
Biopsy proven Fibrillary GN within 3 years of study randomization
Stable Maximum RAAS inhibition X 40 weeks prior to randomization Note: Maximum inhibition will be the discretion of the site PI
eGFR > 25 mls/min
UP/Cr ratio > 2000 mg/gm 5 Note: IF UP/Cr less than 2000 mg/gm, a formal urine collection for total protein can be performed. The total 24-hour will need to >/= 2000mg.
Blood pressure targeted to < 140 at the time of randomization
Patients with MGUS without history of myeloma WILL be eligible.
Patients with monoclonal staining for fibrillary fibers will be excluded
Patients with Type II non-insulin dependent diabetes WILL be eligible provided the renal biopsy does not show nodular Kimmelstiel Wilson lesions
Exclusion
Patients with MGUS and history of myeloma WILL be eligible
Patients with active viral production of either B or C as evidence by historical PCR test positive for active viral shedding
HIV seropositivity
Renal biopsy data with > 5Interstitialxxxx Fibrosis
Patient with active or a known history
Patients with insulin Dependent diabetes mellitus will be excluded Note: Patients diabetes and are well controlled without the need for insulin WILL be eligible for the study.
Patients with Type non-insulin diabetes WILL be eligible provided the renal biopsy does not s nodular Kimmelstiel Wilson lesions.
Patients receiving steroids, MMF, cyc, Azathioprine or other immunosuppressive agent with of study random Note: Wash medications will be allowed at the screening visit
Patients having received Rituximab or cell modifying biologic bbtherapy within 60 months of randomiza
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James A. Tumlin, MD
Organizational Affiliation
NephroNet, Inc.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Georgia Nephrology Research Institute
City
Lawrenceville
State/Province
Georgia
ZIP/Postal Code
30046
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35654563
Citation
Canetta P. Disentangling a Case of Glomerulonephritis with Fibrils. Clin J Am Soc Nephrol. 2022 Jul;17(7):1070-1072. doi: 10.2215/CJN.00630122. Epub 2022 Jun 2. No abstract available.
Results Reference
derived
Learn more about this trial
Comparative and Efficacy Study of ACTHar Gel Alone or in Combination With Tacrolimus in Fibrillary Glomerulopathy
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