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

Sponsor

Cerium Pharmaceuticals, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05696613

Collaborator

(none)

148

Enrollment

Arms

36.9

Anticipated Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Primary Membranous Nephropathy	Drug: SNP-ACTH (1-39) Gel Drug: Rituximab	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

148 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2025

Anticipated Study Completion Date :

Mar 1, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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) [24 months]
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

Secondary Outcome Measures

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]
Adverse events [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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.