Clinical trial NCT05546047: A Study of Acthar Gel Alone or With Tacrolimus to Reduce Proteinuria in Fibrillary Glomerulopathy Patients
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
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Fibrillary Glomerulonephritis
Lead sponsor: NephroNet, Inc.
Sponsor class: OTHER
Collaborators: name: Mallinckrodt
First posted: 2022-09-19
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The change in UP/CR ratio with treatment of Acthar gel 80 units subcutaneous 2 times a week alone
timeFrame: 12 months
measure: The change in UP/CR ratio with treatment of Acthar gel 80 units subcutaneous 2 times a week in combination with oral Tacrolimus
timeFrame: 12 months
Secondary outcomes:
measure: The relative change in protein/creatinine ratio at 24 months
timeFrame: 24 months
measure: Percentage of patients complete or partial response
timeFrame: 12 months
measure: The change in Estimated Glomerular Filtration Rate
timeFrame: 24 months
measure: 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
timeFrame: 12 months
Other outcomes:
measure: To determine if patients with concurrent Type II diabetes mellitus resulted in hyperglycemia, increased proteinuria, loss of renal function or led to immunosuppressive therapies
timeFrame: 24 months
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Department of Medicine Division of Renal Diseases and Hypertension
state: Colorado
city: Lawrenceville
country: United States
facility: Georgia Nephrology DBA Georgia Nephrology Research Institute
state: Georgia
city: New York
country: United States
facility: Columbia University Research Dept of Nephrology
state: New York
city: Bethlehem
country: United States
facility: Northeast Clinical Research Center
state: Pennsylvania
Study officials:
affiliation: NephroNet, Inc.
name: Jeremy Whitson, BS
role: STUDY_DIRECTOR
affiliation: NephroNet, Inc.
name: James Tumlin, MD
role: PRINCIPAL_INVESTIGATOR
References: