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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Fibrillary Glomerulonephritis

Intervention / Treatment
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* Drug: Acthar Gel 80 UNT/ML Injectable Solution


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment with Acthar gel<br>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<br>* Follow up and observation for 12 months off Acthar gel or Acthar gel and Tacrolimus<br>* Other names: Tacrolimus 1.0 mg;|
| Active Comparator: Treatment with combination Acthar gel and Tacrolimus therapy<br>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<br>* Follow up and observation for 12 months off Acthar gel or Acthar gel and Tacrolimus<br>* Other names: Tacrolimus 1.0 mg;|

What is the study measuring?
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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 |