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

Primary Membranous Nephropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05696613
• Other study ID #: ACTH-PMN-301
• Status: Recruiting
• Phase: Phase 3
• Start date: March 13, 2023
• Est. completion date: March 1, 2026

Study information

• Verified date: April 2024
• Source: Cerium Pharmaceuticals, Inc.
• Contact: Nancy Klett, MPH
• Phone: 703-395-0629
• Email: Nancy.Klett[@]ceriumpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 148
• Est. completion date: March 1, 2026
• Est. primary completion date: March 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glomerulonephritis, Membranous
• Kidney Diseases
• Primary Membranous Nephropathy

Intervention

Drug:
• SNP-ACTH (1-39) Gel
Subjects will be randomly assigned in 1:1 treatment allocation ratio to receive the test and reference product.
• Rituximab
Subjects will be randomly assigned in 1:1 treatment allocation ratio to receive the test and reference product.

Locations

Country	Name	City	State
Canada	Regional Kidney Wellness Centre	Brampton	Ontario
India	KLE Hospital	Belgaum	Karnataka
India	PGIMER	Chandigarh	Punjab
India	Vedanta Hospitals	Guntur	Andhra Pradesh
India	Apex Hospitals	Jaipur	Rajasthan
India	SMS Medical College and Hospital	Jaipur	Rajasthan
India	Muljibhai Patel Urological Hospital	Nadiad	Gujarat
India	Saraswati Kidney Care Center	Nagpur	Maharashtra
India	Vijaya Super Speciality Hospital	Nellore	Andhra Pradesh
India	Sir Ganga Ram Hospital	New Delhi	Delhi
India	AIIMS	Raipur	Chhattisgarh
India	Galaxy Hospital	Varanasi	Uttar Pradesh
United States	Fides Clinical Research	Atlanta	Georgia
United States	RecioMed Clinical Research Network, Inc.	Boynton Beach	Florida
United States	Costal Medical Research	Brunswick	Georgia
United States	University of Virginia	Charlottesville	Virginia
United States	Insight Hospital and Medical Center Chicago	Chicago	Illinois
United States	South Florida Nephrology Research	Coral Springs	Florida
United States	Nephrology Associates of Northern Virginia	Fairfax	Virginia
United States	Therafirst Medical Center	Fort Lauderdale	Florida
United States	Prolato Clinical Research Center	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	Academic Medical Research Institute	Los Angeles	California
United States	P&I Clinical Research LLC	Lufkin	Texas
United States	Reliant Medical Research, LLC	Miami	Florida
United States	Vista Health Research, LLC	Miami	Florida
United States	NYU Langone Health	New York	New York
United States	Center for Advanced Kidney Research, PLC	Saint Clair Shores	Michigan
United States	North America Research Institute	San Dimas	California
United States	Genesis Clinical Research	Tampa	Florida
United States	Valiance Clinical Research	Tarzana	California

Sponsors (1)

Lead Sponsor	Collaborator
Cerium Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in urinary protein (Phase 3a)		Change from baseline, months 1, 2, 3, 4, 5, 6, 9, and 12
Primary	Change in Anti-phospholipase A2 receptor (PLA2R) auto-antibody levels (Phase 3a)		Change from baseline, months 1, 2, 3, 4, 6, and 12
Primary	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	Relapse rate at month 12 and month 24.		12 and 24 months
Secondary	Anti-PLA2R (or Anti-THSD7A) auto-antibody levels.		12 and 24 months
Secondary	Estimated glomerular filtration rate (eGFR) with proteinuria levels.		12 and 24 months
Secondary	Adverse events		24 months
Secondary	Incidence of ADAs		24 months
Secondary	Number of patients who achieved a complete remission (CR) or partial remission (PR) at month 12.		12 months
Secondary	Number of patients who achieved a Immunological Response (IR) at month 12.		12 months
Secondary	Assessment of time to achieving CR, PR, IR.		24 months
Secondary	Assessment of time to relapse for patients who achieved CR, PR, IR.		12 and 24 months
Secondary	Duration of time between initial achievement of CR to latest date of observed remission.		24 months