Clinical trial NCT05696613: A Study of SNP-ACTH (1-39) Gel in Patients With Primary Membranous Nephropathy
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Primary Membranous Nephropathy
Keywords: Kidney disease
Rituximab
Nephritis
Melanocortin
Hormones
Glucocorticoids
Glomerular Disease
ACTH
PMN
Lead sponsor: Cerium Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-25
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in urinary protein (Phase 3a)
timeFrame: Change from baseline, months 1, 2, 3, 4, 5, 6, 9, and 12
measure: Change in Anti-phospholipase A2 receptor (PLA2R) auto-antibody levels (Phase 3a)
timeFrame: Change from baseline, months 1, 2, 3, 4, 6, and 12
measure: Complete response of PMN (Phase 3b)
timeFrame: 24 months
Secondary outcomes:
measure: Relapse rate at month 12 and month 24.
timeFrame: 12 and 24 months
measure: Anti-PLA2R (or Anti-THSD7A) auto-antibody levels.
timeFrame: 12 and 24 months
measure: Estimated glomerular filtration rate (eGFR) with proteinuria levels.
timeFrame: 12 and 24 months
measure: Adverse events
timeFrame: 24 months
measure: Incidence of ADAs
timeFrame: 24 months
measure: Number of patients who achieved a complete remission (CR) or partial remission (PR) at month 12.
timeFrame: 12 months
measure: Number of patients who achieved a Immunological Response (IR) at month 12.
timeFrame: 12 months
measure: Assessment of time to achieving CR, PR, IR.
timeFrame: 24 months
measure: Assessment of time to relapse for patients who achieved CR, PR, IR.
timeFrame: 12 and 24 months
measure: Duration of time between initial achievement of CR to latest date of observed remission.
timeFrame: 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Academic Medical Research Institute
state: California
city: San Dimas
country: United States
facility: North America Research Institute
state: California
city: Tarzana
country: United States
facility: Valiance Clinical Research
state: California
city: Boynton Beach
country: United States
facility: RecioMed Clinical Research Network, Inc.
state: Florida
city: Coral Springs
country: United States
facility: South Florida Nephrology Research
state: Florida
city: Fort Lauderdale
country: United States
facility: Therafirst Medical Center
state: Florida
city: Miami
country: United States
facility: Reliant Medical Research, LLC
state: Florida
city: Miami
country: United States
facility: Vista Health Research, LLC
state: Florida
city: Tampa
country: United States
facility: Genesis Clinical Research
state: Florida
city: Atlanta
country: United States
facility: Fides Clinical Research
state: Georgia
city: Brunswick
country: United States
facility: Costal Medical Research
state: Georgia
city: Chicago
country: United States
facility: Insight Hospital and Medical Center Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Saint Clair Shores
country: United States
facility: Center for Advanced Kidney Research, PLC
state: Michigan
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Houston
country: United States
facility: Prolato Clinical Research Center
state: Texas
city: Lufkin
country: United States
facility: P&I Clinical Research LLC
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Fairfax
country: United States
facility: Nephrology Associates of Northern Virginia
state: Virginia
city: Brampton
country: Canada
facility: Regional Kidney Wellness Centre
state: Ontario
city: Guntur
country: India
facility: Vedanta Hospitals
state: Andhra Pradesh
city: Nellore
country: India
facility: Vijaya Super Speciality Hospital
state: Andhra Pradesh
city: Raipur
country: India
facility: AIIMS
state: Chhattisgarh
city: New Delhi
country: India
facility: Sir Ganga Ram Hospital
state: Delhi
city: Nadiād
country: India
facility: Muljibhai Patel Urological Hospital
state: Gujarat
city: Belgaum
country: India
facility: KLE Hospital
state: Karnataka
city: Nagpur
country: India
facility: Saraswati Kidney Care Center
state: Maharashtra
city: Chandigarh
country: India
facility: PGIMER
state: Punjab
city: Jaipur
country: India
facility: SMS Medical College and Hospital
state: Rajasthan
city: Jaipur
country: India
facility: Apex Hospitals
state: Rajasthan
city: Varanasi
country: India
facility: Galaxy Hospital
state: Uttar Pradesh
Study officials:
References: