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

Официальное название

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

Обзор

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.

Подробное описание

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 up to 24 patients randomized to 2 different dose levels of SNP-ACTH (1-39) Gel treatment for 12 months. Dose levels will be:

* approximately 12 patients at 3mg SNP-ACTH Gel subcutaneous (sc) injection 3 times per week; * approximately 12 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.

Вмешательства

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

Первичные конечные точки

• Change in urinary protein (Phase 3a) [Срок оценки: 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) [Срок оценки: Change from baseline, months 1, 2, 3, 4, 6, and 12]
• Complete response of PMN (Phase 3b) [Срок оценки: 24 months]

Вторичные конечные точки (10)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 19 центров

• Academic Medical Research Institute — Los Angeles
• North America Research Institute — San Dimas
• Valiance Clinical Research — Tarzana
• RecioMed Clinical Research Network, Inc. — Boynton Beach
• South Florida Nephrology Research — Coral Springs
• Therafirst Medical Center — Fort Lauderdale
• Reliant Medical Research, LLC — Miami
• Vista Health Research, LLC — Miami
• … и ещё 11 центров

Индия · 11 центров

• Vedanta Hospitals — Guntur
• Vijaya Super Speciality Hospital — Nellore
• AIIMS — Raipur
• Muljibhai Patel Urological Hospital — Nadiād
• KLE Hospital — Belagavi
• Saraswati Kidney Care Center — Nagpur
• Sir Ganga Ram Hospital — New Delhi
• PGIMER — Chandigarh
• … и ещё 3 центра

Канада · 1 центр

• Regional Kidney Wellness Centre — Brampton

Идентификаторы

NCT: NCT05696613 · ACTH-PMN-301

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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