The purpose of this study is to provide the clinician with placebo-controlled safety and efficacy data for the indicated use of Acthar in the treatment of idiopathic membranous nephropathy. Questcor has chosen to evaluate Acthar in those who are treatment-resistant with a low probability of spontaneous remission. The dose regimens selected are designed to be within the FDA approved package insert, and to provide clinically-actionable data consistent with the clinical practice of dose titration.
For complete list of inclusion and exclusion criteria, please refer to contact below.
- Male or female subjects ≥18 years of age, at screening Visit 1. If potential subjects are >75 years of age, discussion between the investigator and the Medical Monitor must take place.
- A history of nephrotic syndrome due to iMN as confirmed by documented results from a renal biopsy performed within 4 years prior to screening Visit 1.
a. If a biopsy has been performed between 4-8 years prior to screening, and if the subject has no signs or symptoms of diabetes or other clinical diagnoses that could suggest a change in renal histology in the opinion of the investigator and the Medical Monitor, the subject is eligible.
- Renal target disease requirements:
a. Total urine protein of >4.0g from the 24-hour urine returned at Visit 1A, AND b. An estimated glomerular filtration rate (eGFR) value >40mL/min/1.73m2 at Visit 1A (as calculated using the abbreviated Modification of Diet in Renal Disease [MDRD] equation, AND c. In order to prevent inclusion of "rapid progressors": i. Screening serum creatinine value no more than 25% higher than the value obtained between 1 to 2 years prior to screening Visit 1A, ii. For subjects that do not have a 1 to 2 year history of serum creatinine data, the following applies: Screening serum creatinine value no more than 15% higher than the value obtained >6 months but <1 year prior to screening Visit 1A, OR Screening serum creatinine value no more than 10% higher than the value obtained ≤6 months prior to screening Visit 1A.
- Any prior course of at least 3 months of treatment with ≥1 of the following standard therapies for iMN: alkylating agents (for example, cyclophosphamide or chlorambucil), rituximab, or calcineurin inhibitors (for example, cyclosporine or tacrolimus).
1. For all therapies except rituximab: a subject must be followed off treatment for ≥3 months and if after follow up period, it was determined that the subject did not achieve a complete or partial remission or suffered a relapse after achieving a partial remission, the subject will be eligible for the study.
2. For subjects whose prior course of treatment was rituximab or a cytotoxic based therapy, a subject must be followed off treatment for ≥6 months and if after the follow up period, it was determined that the subject did not achieve a complete or partial remission or suffered a relapse after achieving a partial remission, the subject will be eligible for the study.
- History of treatment-resistant iMN defined as either having had no remission or having suffered a relapse after achieving either a complete or partial remission to their most recent standard treatment regimen.
- Antihypertensive treatment including use of ACE inhibitors and/or ARB:
1. Unless there is a history of intolerance to ACE inhibitors or ARB therapy, the subject must be treated with at least of these agents,
2. Treatment with ACE inhibitor and/or ARB for ≥3 months prior to screening Visit 1A, with stable maintenance dose for ≥30 days prior to randomization,
3. If treated with other antihypertensive therapies, treatment duration of ≥30 days and stable maintenance dose for ≥7 days prior to screening Visit 1A
- Blood pressure determined by the average of ≥3 seated readings taken ≥5 minutes apart during the screening period at Visit 1A:
1. Mean systolic blood pressure ≤140 mmHg and
2. Mean diastolic blood pressure ≤80 mmHg.
- Use of glucocorticoids or mycophenolate mofetil (MMF) within one month prior to randomization.
- Therapies and/or medications: (a) History of previous use of Acthar for treatment of nephrotic syndrome; (b) Prior sensitivity to Acthar or other porcine protein products; (c) Chronic systemic corticosteroid use, defined as any dose of systemic corticosteroid taken for more than 4 consecutive weeks within 1 month prior to randomization visit (the use of topical, inhaled, or intra-articular corticosteroids is allowed); or (d) Planned treatment with live or live attenuated vaccines once enrolled in the study
- Contraindication to Acthar per package insert: scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenal insufficiency, or adrenocortical hyperfunction. For the purpose of this study: "history" of peptic ulcer is defined as ≤6 months prior to Visit 1A.
- Renal target disease exclusions:
1. Subjects with known diabetic nephropathy or nephrotic syndrome due to a disease or process other than idiopathic membranous nephropathy, or
2. Subjects requiring diagnostic or interventional procedure requiring a contrast agent must delay screening/randomization for at least 7 days.
- History of Systemic Lupus Erythematosus
- Type 1 or Type 2 diabetes mellitus (prior diagnosis of gestational diabetes mellitus is not an exclusion)
- Cardiovascular exclusions:
a. History of or active congestive heart failure (NYHA Functional Classification of CHF Class II through Class IV), or b. History of known dilated cardiomyopathy with left ventricular ejection fraction ≤40%, or c. Occurrence of any of the following within 3 months of screening Visit 1A: i. Unstable angina, ii. Myocardial infarction iii. Coronary artery bypass graft or percutaneous transluminal coronary angioplasty iv. Transient ischemic attack or cerebrovascular disease, or v. unstable arrhythmia.
Last updated: 11/19/2012
NCT ID: NCT01386554