ACTHAR GEL in Patients With Membranous (Class V) Lupus Nephritis
| Status: | Withdrawn |
|---|---|
| Conditions: | Lupus, Lupus, Nephrology |
| Therapuetic Areas: | Immunology / Infectious Diseases, Nephrology / Urology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 5/13/2018 |
| Start Date: | July 2013 |
| End Date: | February 28, 2018 |
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.
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.
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)
We found this trial at
1
site
Columbus, Ohio 43210
Principal Investigator: Brad Rovin, MD
Phone: 614-293-3942
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