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A Study of Acthar Gel Alone or With Tacrolimus to Reduce Proteinuria in Fibrillary Glomerulopathy Patients (FACT)

Primary Purpose

Fibrillary Glomerulonephritis

Status
Active
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Acthar Gel 80 UNT/ML Injectable Solution
Sponsored by
NephroNet, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fibrillary Glomerulonephritis

Eligibility Criteria

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

Inclusion Criteria:

  • Male/Female age > 18
  • Biopsy proven Fibrillary glomerulonephritis within 3 years of study randomization
  • Stable Maximum Renin-Angiotensin-Aldosterone System inhibition times 4 weeks prior to randomization Note: Maximum RAAS inhibition will be left to the discretion of the site Principal Investigator
  • Estimated Glomerular Filtration Rate > 25 mls/min calculate by the Chronic Kidney Disease-EPI formula
  • Protein/creatinine ratio > 2000 mg/gm 5) Note: If protein/creatinine less than 2000 mg/gm, a formal 24- hour urine collection for total protein can be performed. The total 24-hour protein will need to >/= 2000mg.
  • Blood pressure targeted to < 140/90 at the time of randomization
  • Patients with Monoclonal Gammopathy 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 Criteria:

  • Patients with MGUS and history of myeloma will not be eligible
  • Patients with active viral production of either hepatitis B or C as evidence by historical polymerase chain reaction test positive for active viral shedding
  • HIV seropositivity
  • Renal biopsy data with > 50% Interstitial Fibrosis
  • Patient with active or a known history lymphoma
  • Patients with insulin dependent diabetes mellitus will be excluded Note: patients with Type II diabetes mellitus that are well controlled without the need for insulin will be eligible for the study.
  • Patients with Type II non-insulin dependent diabetes will be eligible provided the renal biopsy does not show nodular Kimmelstiel Wilson lesions.
  • Patients receiving steroids, mycophenolate mofetil, cyclophosphamide, Azathioprine or other immunosuppressive agent with 4 weeks of study randomization Note: Washout of these medications will be allowed at the screening visit
  • Patients having received Rituximab or B cell modifying biologic therapy within 6 months of randomization

Sites / Locations

  • Stanford University
  • University of Colorado Anschutz Medical Department of Medicine Division of Renal Diseases and Hypertension
  • Georgia Nephrology DBA Georgia Nephrology Research Institute
  • Columbia University Research Dept of Nephrology
  • Northeast Clinical Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Treatment with Acthar gel

Treatment with combination Acthar gel and Tacrolimus therapy

Arm Description

Group 1 - (17 patients) Acthar gel 80 units 2 times a week alone for 12 months of therapy.

Group 2 - (17 patients) Acthar get 80 units 2 times a week plus oral Tacrolimus 1.0 mg two times a day titrated to trough Tacrolimus levels between 4-6 ng/ml

Outcomes

Primary Outcome Measures

The change in UP/CR ratio with treatment of Acthar gel 80 units subcutaneous 2 times a week alone
The change in protein/creatinine ratio in patients with biopsy proven Fibrillary after 12 months of treatment with treated with Acthar gel (80 units subcutaneous 2 times a week) alone
The change in UP/CR ratio with treatment of Acthar gel 80 units subcutaneous 2 times a week in combination with oral Tacrolimus
The change in protein/creatinine ratio in patients with biopsy proven Fibrillary after 12 months of treatment with treated with Acthar gel 80 units 2 times a week subcutaneous week in combination with oral Tacrolimus 1.0 mg orally two times a day.

Secondary Outcome Measures

The relative change in protein/creatinine ratio at 24 months
The relative change in protein/creatinine at 24 months (12 months after stopping both Acthar and Tacrolimus) in the Acthar gel group and the Acthar gel plus Tacrolimus group.
Percentage of patients complete or partial response
The percentage of patients in the Acthar gel alone versus Acthar gel + Tacrolimus group that achieves complete, partial or clinical responses after 12 months of therapy
The change in Estimated Glomerular Filtration Rate
The change in Estimated Glomerular Filtration Rate between the Acthar gel and Acthar Gel plus Tacrolimus groups after 24 months of treatment with Acthar gel alone or in combination with oral Tacrolimus. In addition, we will also compare the relative change in eGFR between those patients receiving Acthar gel alone with those randomized to combination therapy.
To compare the change in urinary biomarkers of Urinary VEGF 121, 165 189, and206, Urinary MCP-1, Urinary Synaptopodin, Urinary TGF-beta, Urinary Podocalyxin, and Urinary Nephrin
To compare the change in urinary biomarkers at baseline and after 12 months of treatment with Acthar gel alone or in combination with Tacrolimus. The patients urinary biomarker levels after 12 months of therapy will be compared between the Acthar gel alone group and Acthar gel plus Tacrolimus group. Urinary VEGF 121, 165 189, and206 Urinary MCP-1 Urinary Synaptopodin Urinary TGF-beta Urinary Podocalyxin Urinary Nephrin

Full Information

First Posted
August 23, 2022
Last Updated
October 27, 2022
Sponsor
NephroNet, Inc.
Collaborators
Mallinckrodt
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1. Study Identification

Unique Protocol Identification Number
NCT05546047
Brief Title
A Study of Acthar Gel Alone or With Tacrolimus to Reduce Proteinuria in Fibrillary Glomerulopathy Patients
Acronym
FACT
Official Title
A Multicenter, Comparative Safety and Efficacy Study of ACTHar Gel Alone or in Combination With Oral Tacrolimus to Reduce Urinary Proteinuria in Patients With Idiopathic DNAJB9 Positive Fibrillary Glomerulopathy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 14, 2019 (Actual)
Primary Completion Date
October 27, 2023 (Anticipated)
Study Completion Date
October 27, 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
A Multicenter, Comparative Safety and Efficacy Study of Acthar gel alone or in combination with oral Tacrolimus to reduce urinary proteinuria in patients with idiopathic DNAJB9 Positive Fibrillary glomerulopathy.
Detailed Description
A Multicenter, Comparative Safety and Efficacy Study of Acthar gel alone or in combination with oral Tacrolimus to reduce urinary proteinuria in patients with idiopathic DNAJB9 Positive Fibrillary glomerulopathy. This study will be a multi-center, prospective, randomized, open-labeled intervention trial of 34 patients randomized to 52 weeks of ACTHar gel alone or Acthar gel plus oral Tacrolimus.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fibrillary Glomerulonephritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
A 12-month treatment with combination Acthar gel and Tacrolimus therapy will be superior to Acthar gel therapy alone in lowering urinary protein to creatinine ratios in patients with Fibrillary glomerulonephritis
Masking
None (Open Label)
Allocation
Randomized
Enrollment
34 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment with Acthar gel
Arm Type
Active Comparator
Arm Description
Group 1 - (17 patients) Acthar gel 80 units 2 times a week alone for 12 months of therapy.
Arm Title
Treatment with combination Acthar gel and Tacrolimus therapy
Arm Type
Active Comparator
Arm Description
Group 2 - (17 patients) Acthar get 80 units 2 times a week plus oral Tacrolimus 1.0 mg two times a day titrated to trough Tacrolimus levels between 4-6 ng/ml
Intervention Type
Drug
Intervention Name(s)
Acthar Gel 80 UNT/ML Injectable Solution
Other Intervention Name(s)
Tacrolimus 1.0 mg
Intervention Description
Follow up and observation for 12 months off Acthar gel or Acthar gel and Tacrolimus
Primary Outcome Measure Information:
Title
The change in UP/CR ratio with treatment of Acthar gel 80 units subcutaneous 2 times a week alone
Description
The change in protein/creatinine ratio in patients with biopsy proven Fibrillary after 12 months of treatment with treated with Acthar gel (80 units subcutaneous 2 times a week) alone
Time Frame
12 months
Title
The change in UP/CR ratio with treatment of Acthar gel 80 units subcutaneous 2 times a week in combination with oral Tacrolimus
Description
The change in protein/creatinine ratio in patients with biopsy proven Fibrillary after 12 months of treatment with treated with Acthar gel 80 units 2 times a week subcutaneous week in combination with oral Tacrolimus 1.0 mg orally two times a day.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
The relative change in protein/creatinine ratio at 24 months
Description
The relative change in protein/creatinine at 24 months (12 months after stopping both Acthar and Tacrolimus) in the Acthar gel group and the Acthar gel plus Tacrolimus group.
Time Frame
24 months
Title
Percentage of patients complete or partial response
Description
The percentage of patients in the Acthar gel alone versus Acthar gel + Tacrolimus group that achieves complete, partial or clinical responses after 12 months of therapy
Time Frame
12 months
Title
The change in Estimated Glomerular Filtration Rate
Description
The change in Estimated Glomerular Filtration Rate between the Acthar gel and Acthar Gel plus Tacrolimus groups after 24 months of treatment with Acthar gel alone or in combination with oral Tacrolimus. In addition, we will also compare the relative change in eGFR between those patients receiving Acthar gel alone with those randomized to combination therapy.
Time Frame
24 months
Title
To compare the change in urinary biomarkers of Urinary VEGF 121, 165 189, and206, Urinary MCP-1, Urinary Synaptopodin, Urinary TGF-beta, Urinary Podocalyxin, and Urinary Nephrin
Description
To compare the change in urinary biomarkers at baseline and after 12 months of treatment with Acthar gel alone or in combination with Tacrolimus. The patients urinary biomarker levels after 12 months of therapy will be compared between the Acthar gel alone group and Acthar gel plus Tacrolimus group. Urinary VEGF 121, 165 189, and206 Urinary MCP-1 Urinary Synaptopodin Urinary TGF-beta Urinary Podocalyxin Urinary Nephrin
Time Frame
12 months
Other Pre-specified Outcome Measures:
Title
To determine if patients with concurrent Type II diabetes mellitus resulted in hyperglycemia, increased proteinuria, loss of renal function or led to immunosuppressive therapies
Description
To determine whether Acthar gel therapy resulted in hyperglycemia in patients with concurrent Diabetes and whether that led to early termination from the study. We will also determine whether the presence of diabetes led to increased proteinuria over time, led to more rapid decline in renal function and altered the response to immunosuppressive therapy.
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male/Female age > 18 Biopsy proven Fibrillary glomerulonephritis within 3 years of study randomization Stable Maximum Renin-Angiotensin-Aldosterone System inhibition times 4 weeks prior to randomization Note: Maximum RAAS inhibition will be left to the discretion of the site Principal Investigator Estimated Glomerular Filtration Rate > 25 mls/min calculate by the Chronic Kidney Disease-EPI formula Protein/creatinine ratio > 2000 mg/gm 5) Note: If protein/creatinine less than 2000 mg/gm, a formal 24- hour urine collection for total protein can be performed. The total 24-hour protein will need to >/= 2000mg. Blood pressure targeted to < 140/90 at the time of randomization Patients with Monoclonal Gammopathy 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 Criteria: Patients with MGUS and history of myeloma will not be eligible Patients with active viral production of either hepatitis B or C as evidence by historical polymerase chain reaction test positive for active viral shedding HIV seropositivity Renal biopsy data with > 50% Interstitial Fibrosis Patient with active or a known history lymphoma Patients with insulin dependent diabetes mellitus will be excluded Note: patients with Type II diabetes mellitus that are well controlled without the need for insulin will be eligible for the study. Patients with Type II non-insulin dependent diabetes will be eligible provided the renal biopsy does not show nodular Kimmelstiel Wilson lesions. Patients receiving steroids, mycophenolate mofetil, cyclophosphamide, Azathioprine or other immunosuppressive agent with 4 weeks of study randomization Note: Washout of these medications will be allowed at the screening visit Patients having received Rituximab or B cell modifying biologic therapy within 6 months of randomization
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeremy Whitson, BS
Organizational Affiliation
NephroNet, Inc.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
James Tumlin, MD
Organizational Affiliation
NephroNet, Inc.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Colorado Anschutz Medical Department of Medicine Division of Renal Diseases and Hypertension
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Georgia Nephrology DBA Georgia Nephrology Research Institute
City
Lawrenceville
State/Province
Georgia
ZIP/Postal Code
30046
Country
United States
Facility Name
Columbia University Research Dept of Nephrology
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Northeast Clinical Research Center
City
Bethlehem
State/Province
Pennsylvania
ZIP/Postal Code
18017
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Study of Acthar Gel Alone or With Tacrolimus to Reduce Proteinuria in Fibrillary Glomerulopathy Patients

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