Acthar for Treatment of Proteinuria in Membranous Nephropathy Patients
Condition: Proteinuria; Idiopathic Membranous Nephropathy
MeSH terms: Kidney Diseases; Proteinuria; Nephrotic Syndrome; Glomerulonephritis, Membranous
Intervention: Repository Corticotropin Injection; Placebo
Intervention description: Acthar given SC for 6 months; Placebo contains the same inactive ingredients as that used for H.P. Acthar Gel without the API.
Placebo given SC for 6 months (80 U two times a week).
Intervention MeSH terms: Adrenocorticotropic Hormone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: H.P. Acthar Gel; Acthar; nephrotic syndrome; idiopathic membranous nephropathy; proteinuria

Summary:

      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.
    

Eligibility criteria:

        For complete list of inclusion and exclusion criteria, please refer to contact below.

        Inclusion 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.

        Exclusion Criteria:

          -  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.