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

This study is currently recruiting participants.
Verified February 2014 by Ohio State University
Sponsor:
Collaborator:
Questcor Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Brad Rovin, MD, Ohio State University
ClinicalTrials.gov Identifier:
NCT01926054
First received: July 15, 2013
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
SLE Glomerulonephritis Syndrome, WHO Class V
Drug: Acthar gel
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Randomized Phase IV Study of the Safety and Efficacy of ACTHAR GEL in Patients With Membranous (Class V) Lupus Nephritis

Resource links provided by NLM:


Further study details as provided by Ohio State University:

Primary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: Yes ]
    Measuring adverse events and serious adverse events taking Acthar Gel in Class V lupus nephritis

  • Change in laboratory data [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: Yes ]
    changes in laboratory parameters, and metabolic side effects such as hyperglycemia, hypokalemia, and hyperlipidemia

  • Renal Response to Acthar Gel [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    Change in Proteinuria and serum creatinine


Secondary Outcome Measures:
  • Change in remission [ Time Frame: Month 6 and Month 12 ] [ Designated as safety issue: No ]
    To determine the duration of complete and partial remission after study drug is stopped

  • Change baseline SLE laboratory [ Time Frame: Baseline and month 6 ] [ Designated as safety issue: No ]
    To determine the effect of Acthar Gel on baseline levels of anti-double stranded DNA (dsDNA) antibodies and complement components C3 and C4

  • Change in extra-renal systemic lupus erythematosus disease activity index [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    To determine the effect of Acthar Gel on the patients global assessment score, the physicians global assessments score and xSLEDAI


Other Outcome Measures:
  • reduction of urine protein to creatinine ratio [ Time Frame: week 8 and month 6 ] [ Designated as safety issue: No ]
    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

  • change urine monocyte chemotactic protein-1 and urine vascular endothelial growth factor [ Time Frame: Baseline and 6 month ] [ Designated as safety issue: No ]
    To determine change from baseline of urine monocyte chemotactic protein-1 (uMCP1) and urine vascular endothelial growth factor (uVEGF) at 3 and 6 months

  • percent of patients who have renal and non renal flares [ Time Frame: baseline and month 12 ] [ Designated as safety issue: No ]
    To determine the % of patients who have renal flares during treatment and during follow-up


Estimated Enrollment: 25
Study Start Date: July 2013
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01926054

Locations
United States, Ohio
The Ohio State University Wexner Medical Center, Nephrology Clinical Trials Unit Recruiting
Columbus, Ohio, United States, 43210
Contact: Alicia A Lykins    614-293-6205    Alicia.Lykins@osumc.edu   
Contact: Brad H Rovin, MD    614-293-4997    Brad.Rovin@osumc.edu   
Principal Investigator: Brad Rovin, MD         
Sub-Investigator: Samir Parikh, MD         
Sponsors and Collaborators
Ohio State University
Questcor Pharmaceuticals, Inc.
Investigators
Principal Investigator: Brad H Rovin, MD The Ohio State University Wexner Medical Center, Division of Nephrology
  More Information

No publications provided

Responsible Party: Brad Rovin, MD, Principle Investigator, Ohio State University
ClinicalTrials.gov Identifier: NCT01926054     History of Changes
Other Study ID Numbers: 2013H0121
Study First Received: July 15, 2013
Last Updated: February 10, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Glomerulonephritis
Lupus Nephritis
Nephritis
Lupus Erythematosus, Systemic
Kidney Diseases
Urologic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adrenocorticotropic Hormone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014