Acthar for Treatment of Proteinuria in Membranous Nephropathy Patients
Trial ID or NCT#
Status
Purpose
The purpose of this study is to provide nephrologists with additional clinical evidence regarding the efficacy and safety of Acthar in subjects with treatment-resistant idiopathic membranous nephropathy. Approximately sixty (60) subjects will be randomized in this double-blind, parallel-group, placebo-controlled, multicenter study comparing Acthar and Placebo administered 2 times per week for a 24-week treatment period followed by a 24-week observation period. The primary objective of this study is to assess the proportion of treatment-resistant subjects (defined as subjects who either have had no response or have suffered a relapse after achieving a partial response to their most recent standard treatment regimen) who have a complete or partial remission of proteinuria in nephrotic syndrome due to idiopathic membranous nephropathy after 24 weeks of treatment.
Official Title
A Randomized, Placebo-Controlled, Parallel-Group, Double-Blind Study of H.P. Acthar Gel (Acthar) in Treatment-Resistant Subjects With Persistent Proteinuria and Nephrotic Syndrome Due to Idiopathic Membranous Nephropathy (iMN)
Eligibility Criteria
- * Male or female subjects ≥18 years of age, at screening Visit 1:
- a. If potential subjects are \>75 years of age, discussion between the investigator and the Medical Monitor must take place;* Body mass index ≤40 kg/m2, at screening Visit 1;* 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:
- 1. Total urine protein of ≥3.0g (≥3000mg) from the 24-hour urine returned at Visit 1A, AND. 2. An estimated glomerular filtration rate (eGFR) value \>25mL/min/1.73m2 at Visit 1A (as calculated using the abbreviated Modification of Diet in Renal Disease \[MDRD\] equation.* Any prior course of at least 1 month of treatment with ≥1 of an immunosuppressant therapy(ies) for iMN:
- 1. Subjects must be followed for at least 3 months after treatment prior to screening with the exception of rituximab or a cytotoxic based therapy, where the follow-up period is 6 months after treatment. If after follow-up 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. If in the investigator's opinion, the subject should be enrolled prior to meeting the follow-up period criteria and the decrease in proteinuria is no longer occurring, discussion between the investigator and the Medical Monitor must take place for approval to enter screening.* History of treatment-resistant iMN defined as either having had no remission or having suffered a relapse after achieving a partial remission to their most recent standard treatment regimen as defined in the Definition of Response Status Table despite treatment with at least 1 month of treatment with a prior therapy for iMN. Note the following:
- a. If the subject has been treated with prior standard therapy and can no longer be re-treated with any component of that therapy, regardless of whether a complete or partial remission was achieved, then the subject may be eligible, but approval from the Medical Monitor is required.
- i. For example, if early discontinuation of standard therapy occurred because of a serious adverse event (Grade 3 or 4) during the treatment, regardless of whether a partial or complete remission was achieved, then the subject may be eligible.
- b. If (a) does not apply, and the subject did not have either a partial or complete remission to the most recent treatment regimen, then the subject is eligible.
- c. If (a) does not apply, and the subject achieved a partial remission from the most recent treatment regimen, and later relapse occurred, then the subject is eligible.* Antihypertensive treatment including use of ACE inhibitors and/or ARB:
- a. Unless there is a history of intolerance to ACE inhibitors or ARB therapy, the subject must be treated with at least one of these agents.
- b. 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.
- c. 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.
- * Therapies and/or medications:
- 1. History of previous use of Acthar for treatment of nephrotic syndrome; 2. Prior sensitivity to Acthar or other porcine protein products; or 3. Planned treatment with live or live attenuated vaccines once enrolled in the study.* Contraindication to Acthar per Prescribing Information: scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, or adrenocortical hyperfunction.
- a. 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).* History of Deep Vein Thrombosis (DVT) ≤6 months prior to screening Visit 1A.* Presence of renal vein thrombosis:
- 1. Known current diagnosis by ultrasound, magnetic resonance imaging (MRI) or computed tomography scan; 2. Signs or symptoms consistent with occurrence of acute renal vein thrombosis (hematuria in combination with flank pain and \>30% unexplained acute rise in serum creatinine) with renal vein thrombosis confirmed by ultrasound, MRI or computed tomography scan.* Cardiovascular exclusions:
- 1. History of or active congestive heart failure (NYHA Functional Classification of CHF Class II through Class IV), or. 2. History of known dilated cardiomyopathy with left ventricular ejection fraction ≤40%, or. 3. 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. v. unstable arrhythmia.
Investigator(s)
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