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

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

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 Overview

• Status: Active, not recruiting
• Conditions: Fibrillary Glomerulonephritis
• Intervention / Treatment: Drug: Acthar Gel 80 UNT/ML Injectable Solution

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.

• Study Type: Interventional
• Enrollment (Anticipated): 34
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Department of Medicine Division of Renal Diseases and Hypertension
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Georgia Nephrology DBA Georgia Nephrology Research Institute
  • New York
    • New York, New York, United States, 10032
      • Columbia University Research Dept of Nephrology
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Northeast Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment with Acthar gel; Group 1 - (17 patients) Acthar gel 80 units 2 times a week alone for 12 months of therapy.	Drug: Acthar Gel 80 UNT/ML Injectable Solution; Follow up and observation for 12 months off Acthar gel or Acthar gel and Tacrolimus; Other Names: Tacrolimus 1.0 mg
Active Comparator: Treatment with combination Acthar gel and Tacrolimus 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	Drug: Acthar Gel 80 UNT/ML Injectable Solution; Follow up and observation for 12 months off Acthar gel or Acthar gel and Tacrolimus; Other Names: Tacrolimus 1.0 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	12 months
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.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	24 months
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	12 months
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.	24 months
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	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine if patients with concurrent Type II diabetes mellitus resulted in hyperglycemia, increased proteinuria, loss of renal function or led to immunosuppressive therapies	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.	24 months

Collaborators and Investigators

• Sponsor: NephroNet, Inc.
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: James Tumlin, MD, NephroNet, Inc.; Study Director: Jeremy Whitson, BS, NephroNet, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2019
• Primary Completion (Anticipated): October 27, 2023
• Study Completion (Anticipated): October 27, 2024

Study Registration Dates

• First Submitted: August 23, 2022
• First Submitted That Met QC Criteria: September 15, 2022
• First Posted (Actual): September 19, 2022

Study Record Updates

• Last Update Posted (Actual): October 31, 2022
• Last Update Submitted That Met QC Criteria: October 27, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Urological Manifestations; Urination Disorders; Nephritis; Proteinuria; Glomerulonephritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: NN-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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