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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: SLE Glomerulonephritis Syndrome, WHO Class V
• Intervention / Treatment: Drug: Acthar gel

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center, Nephrology Clinical Trials Unit

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:

• 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)

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: Acthar Gel 80 IU SC BIW; 80 IU administered subcutaneously BIW for 6 months	Drug: Acthar gel
Active Comparator: Acthar Gel 80 IU SC TIW; 80 IU administered subcutaneously TIW for 6 months	Drug: Acthar gel

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
reduction of urine protein to creatinine ratio	To determine if a reduction of the urine protein-to-creatinine ratio (uPCR) of an intended 24-hour of ≥25% at 8 weeks predicts complete or partial response at 6 months	week 8 and month 6
change urine monocyte chemotactic protein-1 and urine vascular endothelial growth factor	To determine change from baseline of urine monocyte chemotactic protein-1 (uMCP1) and urine vascular endothelial growth factor (uVEGF) at 3 and 6 months	Baseline and 6 month
percent of patients who have renal and non renal flares	To determine the % of patients who have renal flares during treatment and during follow-up	baseline and month 12

Collaborators and Investigators

• Sponsor: Ohio State University
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Brad H Rovin, MD, The Ohio State University Wexner Medical Center, Division of Nephrology

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): February 28, 2018

Study Registration Dates

• First Submitted: July 15, 2013
• First Submitted That Met QC Criteria: August 16, 2013
• First Posted (Estimate): August 20, 2013

Study Record Updates

• Last Update Posted (Actual): May 11, 2018
• Last Update Submitted That Met QC Criteria: May 5, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Glomerulonephritis; Nephritis; Lupus Nephritis
• Other Study ID Numbers: 2013H0121