A Study of SNP-ACTH (1-39) Gel in Patients With Primary Membranous Nephropathy

A Phase 3 Superiority Study Comparing the Safety and Efficacy of SNP-ACTH (1-39) Gel Compared to Rituximab and FDA Approved Biosimilars in Adults With Primary Membranous Nephropathy (PMN) in a Two-Phase Adaptive Trial Design

The goal of the Phase 3a part of this clinical trial is to determine the optimal dose that will be used in the Phase 3b part of this clinical trial. The goal of the Phase 3b part is to assess the efficacy of SNP-ACTH (1-39) Gel relative to rituximab in patients with primary membranous nephropathy (PMN) at month 24.

Study Overview

• Status: Recruiting
• Conditions: Primary Membranous Nephropathy
• Intervention / Treatment: Drug: SNP-ACTH (1-39) Gel; Drug: Rituximab

Detailed Description

This head-to-head, open-label, 2-phase superiority trial compares SNP-ACTH (1-39) Gel to rituximab in the treatment of PMN that commences with an adaptive trial design for dose finding. The trial will be divided into 2 parts: Phase 3a and Phase 3b.

Dose finding Phase 3a part of the study will enroll a total of 16 patients randomized to 2 different dose levels of SNP-ACTH (1-39) Gel treatment for 12 months. Dose levels will be:

• 8 patients at 3mg SNP-ACTH Gel subcutaneous (sc) injection 3 times per week;
• 8 patients at 5mg SNP-ACTH Gel sc injection 3 times per week

Data from the Phase 3a part of the study will be assessed at regular intervals (at months 2, 3, 4, 5, 6, 9, 12) and will inform the dose selection for the Phase 3b. The optimal dose will be determined based on a risk/benefit assessment from data obtained from the Phase 3a part of the study, with the earliest assessment being conducted after all patients have completed at least 2 months of therapy.

The Phase 3b part of the study will enroll 132 patients randomized 1:1 to either 12 months of 1g Rituximab therapy (2 treatment cycles at month 1 and month 6) or 12 months of SNP-ACTH (1-39) Gel treatment at the dose level determined in the Phase 3a.

• Study Type: Interventional
• Enrollment (Estimated): 148
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Nancy Klett, MPH; Phone Number: 703-395-0629; Email: Nancy.Klett@ceriumpharma.com

Study Locations

• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6T 0H9
      • Recruiting
      • Regional Kidney Wellness Centre
• India
  • Andhra Pradesh
    • Guntur, Andhra Pradesh, India, 522001
      • Recruiting
      • Vedanta Hospitals
    • Nellore, Andhra Pradesh, India, 524001
      • Recruiting
      • Vijaya Super Speciality Hospital
  • Chhattisgarh
    • Raipur, Chhattisgarh, India, 492099
      • Recruiting
      • AIIMS
  • Delhi
    • New Delhi, Delhi, India, 10060
      • Recruiting
      • Sir Ganga Ram Hospital
  • Gujarat
    • Nadiād, Gujarat, India
      • Recruiting
      • Muljibhai Patel Urological Hospital
  • Karnataka
    • Belgaum, Karnataka, India, 590010
      • Recruiting
      • KLE Hospital
  • Maharashtra
    • Nagpur, Maharashtra, India, 440015
      • Recruiting
      • Saraswati Kidney Care Center
  • Punjab
    • Chandigarh, Punjab, India, 160012
      • Recruiting
      • PGIMER
  • Rajasthan
    • Jaipur, Rajasthan, India, 302004
      • Recruiting
      • SMS Medical College and Hospital
    • Jaipur, Rajasthan, India, 302017
      • Recruiting
      • Apex Hospitals
  • Uttar Pradesh
    • Varanasi, Uttar Pradesh, India, 221010
      • Recruiting
      • Galaxy Hospital
• United States
  • California
    • Los Angeles, California, United States, 90022
      • Recruiting
      • Academic Medical Research Institute
    • San Dimas, California, United States, 91773
      • Recruiting
      • North America Research Institute
    • Tarzana, California, United States, 91356
      • Recruiting
      • Valiance Clinical Research
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • Recruiting
      • Reciomed Clinical Research Network, Inc.
    • Coral Springs, Florida, United States, 33071
      • Recruiting
      • South Florida Nephrology Research
    • Fort Lauderdale, Florida, United States, 33308
      • Recruiting
      • Therafirst Medical Center
    • Miami, Florida, United States, 33165
      • Recruiting
      • Reliant Medical Research, LLC
    • Miami, Florida, United States, 33176
      • Recruiting
      • Vista Health Research, LLC
    • Tampa, Florida, United States, 33603
      • Recruiting
      • Genesis Clinical Research
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Recruiting
      • Fides Clinical Research
    • Brunswick, Georgia, United States, 31520
      • Recruiting
      • Costal Medical Research
  • Illinois
    • Chicago, Illinois, United States, 60615
      • Recruiting
      • Insight Hospital and Medical Center Chicago
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
  • Michigan
    • Saint Clair Shores, Michigan, United States, 48080
      • Recruiting
      • Center for Advanced Kidney Research, PLC
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
      • Contact: Nancy Klett
  • Texas
    • Houston, Texas, United States, 77054
      • Recruiting
      • Prolato Clinical Research Center
    • Lufkin, Texas, United States, 75904
      • Recruiting
      • P&I Clinical Research LLC
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia
    • Fairfax, Virginia, United States, 22033
      • Recruiting
      • Nephrology Associates of Northern Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Biopsy-proven membranous glomerulonephritis or a diagnosis of MN in patients with Nephrotic Syndrome and a positive anti PLA2R antibody test.
• Patients classified to be at a High Risk for progressive loss of kidney function, as defined by Kidney Disease Improving Global Outcomes (KDIGO) 2021-Glomerular Diseases Guideline.
• eGFR by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula ≥40 mL/min/1.73 m^2
• Patients who have had CR or PR in response to immunosuppressive therapy, but then relapsed can participate in the study if it has been more than 3 months since their last dose of high dose glucocorticoids, calcineurin inhibitors or mycophenolate mofetil
• Patients who have had CR or PR in response to IS therapy, but then relapsed can participate in the study if it has been more than 6 months since their last dose of chlorambucil or cyclophosphamide
• Patients who have had CR or PR in response to immunosuppressive therapy, but then relapsed can participate in the study if it has been more than 12 months since their last dose of rituximab.
• Life expectancy > 24 months.
• Other inclusion criteria may apply.

Exclusion Criteria:

• Secondary membranous nephropathy as defined by history, physical exam, kidney biopsy results or serologies.
• Patients who have had a ≥ 50% reduction in serum titers of PLA2R auto-antibody within 1 year before screening.
• Type 1 or 2 diabetes mellitus
• Patients who must be initiated on drugs likely to affect renal function if not properly dosed.
• Surgery within 1 month of study entry
• History of sensitivity to proteins of porcine origin.
• Other exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 3a Cohort 1; 3 mg SNP-ACTH Gel sc injection 3 times per week	Drug: SNP-ACTH (1-39) Gel; Subjects will be randomly assigned in 1:1 treatment allocation ratio to receive the test and reference product.
Experimental: Phase 3a Cohort 2; 5 mg SNP-ACTH Gel sc injection 3 times per week	Drug: SNP-ACTH (1-39) Gel; Subjects will be randomly assigned in 1:1 treatment allocation ratio to receive the test and reference product.
Experimental: Phase 3b Cohort 1; Dose level to be confirmed once Phase 3a part is completed	Drug: SNP-ACTH (1-39) Gel; Subjects will be randomly assigned in 1:1 treatment allocation ratio to receive the test and reference product.
Active Comparator: Phase 3b Cohort 2; Rituximab arm: Patients randomized to the rituximab arm will receive 1 g IV infusion on T0 (after baseline measures are collected) and day 15. A second course of rituximab 1g IV infusion will be administered 6 months after the first rituximab infusion and an additional 1 g IV infusion 14 days following the first 6-month infusion.	Drug: Rituximab; Subjects will be randomly assigned in 1:1 treatment allocation ratio to receive the test and reference product.; Other Names: Rituxan or other biosimilars

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in urinary protein (Phase 3a)		Change from baseline, months 1, 2, 3, 4, 5, 6, 9, and 12
Change in Anti-phospholipase A2 receptor (PLA2R) auto-antibody levels (Phase 3a)		Change from baseline, months 1, 2, 3, 4, 6, and 12
Complete response of PMN (Phase 3b)	Reduction of proteinuria to ≤0.3 g/24 hours as measured by urine protein/creatinine ratio obtained from a 24-hour urine collection with stable renal function defined as a <15% decline in eGFR at the time of endpoint assessment	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events	24 months
Relapse rate at month 12 and month 24.	12 and 24 months
Anti-PLA2R (or Anti-THSD7A) auto-antibody levels.	12 and 24 months
Estimated glomerular filtration rate (eGFR) with proteinuria levels.	12 and 24 months
Incidence of ADAs	24 months
Number of patients who achieved a complete remission (CR) or partial remission (PR) at month 12.	12 months
Number of patients who achieved a Immunological Response (IR) at month 12.	12 months
Assessment of time to achieving CR, PR, IR.	24 months
Assessment of time to relapse for patients who achieved CR, PR, IR.	12 and 24 months
Duration of time between initial achievement of CR to latest date of observed remission.	24 months

Collaborators and Investigators

• Sponsor: Cerium Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: December 29, 2022
• First Submitted That Met QC Criteria: January 13, 2023
• First Posted (Actual): January 25, 2023

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Rituximab; Glucocorticoids; Nephritis; Kidney disease; Glomerular Disease; PMN; ACTH; Hormones; Melanocortin
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Glomerulonephritis, Membranous; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Immunological; Rituximab; Adrenocorticotropic Hormone
• Other Study ID Numbers: ACTH-PMN-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No