ACTHAR GEL in Patients With Membranous (Class V) Lupus Nephritis

Study Overview
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Brief Summary
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This is an open-label, randomized, multi-center, Phase IV study of Acthar Gel in patients with biopsy-proven membranous (Class V) lupus nephritis (LN) aimed at providing proof-of-concept data that Acthar is a safe and effective therapy for membranous LN. Class V LN is a secondary form of membranous nephropathy, and occurs in 8-20% of patients with LN. Two different doses of Acthar Gel will be tested. The active intervention phase of this study will take place over 6 months, and follow-up will occur over the following 6 months. Efficacy and safety of the use of Acthar Gel for treatment of membranous LN will be assessed and analyzed throughout the course of the study by laboratory testing, physical exams, and other evaluation tools. Subjects will be closely monitored for adverse effects associated with the use of Acthar gel and if necessary study drug dosing will be reduced. The anticipated benefits to subjects are a complete renal response rate of 40% at 6 months showing superiority over the published complete remission rates of the currently used immunosuppressive therapies, and no unexpected toxicity signals. Pure Class V LN affects a significant number of systemic lupus erythematosus (SLE) patients and although it is less aggressive than proliferative forms of LN it still causes important renal and non-renal morbidity and mortality over time, especially in patients who remain nephrotic. The therapy of Class V LN is not clear, and currently used therapies are highly toxic because of immunosuppression, risk of infertility, and risk of future malignancy. Additionally, these therapies are only modestly effective in inducing remissions of Class V LN. There is thus an unmet need for a more effective and less toxic treatment for Class V LN.

Official Title
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An Open Label Randomized Phase IV Study of the Safety and Efficacy of ACTHAR GEL in Patients With Membranous (Class V) Lupus Nephritis

Conditions
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SLE Glomerulonephritis Syndrome, WHO Class V

Intervention / Treatment
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* Drug: Acthar gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years of age who have pure Class V LN or Class V+II LN diagnosed by a kidney biopsy within 4 months of screening. If a patient has segmental glomerular scarring indicative of previous Class III or IV lesions, but no evidence of current Class III or IV activity, and only the Class V component is active, they can be enrolled, despite having a mandatory ISN/RPA classification of Class V + III or IV Proteinuria ≥ 3 g/d despite adequate blood pressure control defined as systolic blood pressure ≤ 130 mm Hg 75% of the time, per the clinical judgment of the site investigator. Serum creatinine < 2 mg/dl or eGFR > 30 ml/minute Exclusion Criteria: Patients < 18 years of age Pregnancy or planning to become pregnant anytime throughout their participation in the trial, up until 30 days after last dose of study drug. Kidney biopsy with active Class III or IV LN More than 50% interstitial fibrosis and/or glomerulosclerosis on kidney biopsy Patients with hepatitis B, C, HIV, TB or other active and chronic infections at the time of screening Patients with liver disease and transaminases greater than 2.5 times the upper limit of normal of the laboratory, patients with diabetes mellitus type I or II, patients with refractory hypokalemia, patients with Cushing's Disease or Syndrome Patients who have been treated with cyclophosphamide, cyclosporine A, tacrolimus, B-cell depleting therapies, or experimental therapies including biologics within 6 months of screening Patients with active neuropsychiatric lupus, lupus pneumonitis, lupus vasculitis at screening Patients with high or very high extra-renal lupus activity defined as an xSLEDAI score greater than 10 at the time of screening Patients who have received high-dose intravenous methylprednisolone (1 g cumulative) within 3 months of screening Patients currently receiving, or who have received MMF or AZA in the 3 months preceding enrollment for extra-renal SLE. Patients who have received methotrexate or who are receiving methotrexate and it can be discontinued will be eligible; if methotrexate cannot be stopped safely, the patient will not be eligible. Patients currently receiving more than 20 mg/d prednisone that cannot be safely reduced to 20mg/d or less beginning at least one month before enrollment on day 0 Patients who are not on a stable dose of Anti-Malarials and/or Anti-hypertensives at least one month preceding baseline visit and during the study. (Refer to allowed medication section)

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Acthar Gel 80 IU SC BIW<br>80 IU administered subcutaneously BIW for 6 months | Drug: Acthar gel<br> <br> |
| Active Comparator: Acthar Gel 80 IU SC TIW<br>80 IU administered subcutaneously TIW for 6 months | Drug: Acthar gel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | Measuring adverse events and serious adverse events taking Acthar Gel in Class V lupus nephritis | Baseline and Month 12 | 
| Change in laboratory data | changes in laboratory parameters, and metabolic side effects such as hyperglycemia, hypokalemia, and hyperlipidemia | Baseline and Month 12 | 
| Renal Response to Acthar Gel | Change in Proteinuria and serum creatinine | Baseline and Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in remission | To determine the duration of complete and partial remission after study drug is stopped | Month 6 and Month 12 | 
| Change baseline SLE laboratory | To determine the effect of Acthar Gel on baseline levels of anti-double stranded DNA (dsDNA) antibodies and complement components C3 and C4 | Baseline and month 6 | 
| Change in extra-renal systemic lupus erythematosus disease activity index | To determine the effect of Acthar Gel on the patients global assessment score, the physicians global assessments score and xSLEDAI | Baseline and Month 6 |