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

Cerium Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Primary Membranous Nephropathy

Treatments: Drug: SNP-ACTH (1-39) Gel; Drug: Rituximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05696613

ACTH-PMN-301

Details and patient eligibility

About

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.

Full 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.

Enrollment: 148 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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148 participants in 4 patient groups

Phase 3a Cohort 1

Experimental group

Description:

3 mg SNP-ACTH Gel sc injection 3 times per week

Treatment:

Drug: SNP-ACTH (1-39) Gel

Phase 3a Cohort 2

Experimental group

Description:

5 mg SNP-ACTH Gel sc injection 3 times per week

Treatment:

Drug: SNP-ACTH (1-39) Gel

Phase 3b Cohort 1

Experimental group

Description:

Dose level to be confirmed once Phase 3a part is completed

Treatment:

Drug: SNP-ACTH (1-39) Gel

Phase 3b Cohort 2

Active Comparator group

Description:

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.

Treatment:

Drug: Rituximab