CTRI/2023/06/053691 [Registered on: 08/06/2023] Trial Registered Prospectively
Last Modified On:
18/08/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
Head-to-head, open-label, superiority trial compares SNP-ACTH (1-39) Gel to rituximab in treatment of PMN that commences with an adaptive trial design.
Scientific Title of Study
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 Research Department-Basement, 357B, Bengaluru Bellary Road, Near to HDFC bank, Yelahanka Town, Opposite RR Gold Palace Bangalore, Karnataka - 560064, India
Bangalore KARNATAKA
9901996744
drsanjaysri872@gmail.com
Dr Dhananjay Sinha
Galaxy Hospital
4th floor M.S. Chamber, CT room, Galaxy Hospital, Plot No. 4,5,6,7, Dayal Enclave Mahmoorganj Rd, Near Railway Station, Mahmoorganj, Uttar Pradesh - 221010, India.
Varanasi UTTAR PRADESH
9415304564
dksinha15@gmail.com
Dr Shreedhar CG
Institute of Nephro Urology
Room No. 08, Department of Nephrology, Institute of Nephro Urology, XH6F Q47, Victoria Hospital Campus, Alur Venkata Rao Rd, New Tharagupet, Bengaluru- Karnataka 560002, India. Bangalore KARNATAKA
9535246939
drsreedharcg@gmail.com
Dr Ramaswami Sethuraman
KG Hospital and Post Graduate Medical lnstitute and Research Centre
No. 5, Government Arts College Road, Coimbatore, Tamil Nadu, lndia - 641018 Coimbatore TAMIL NADU
9600900078
ramaswami.sethuraman@gmail.com
Dr Ritesh Verneker
KLES Dr. Prabhakar Kore Hospital and Medical Research Centre
G2 Sharavati Floor SMO Office, KLES Dr. Prabhakar Kore Hospital and MRC, Belagavi, Karnataka – 590010, India.
Belgaum KARNATAKA
8312470400
riteshvernekar@gmail.com
Dr Abhijit Konnur
Muljibhai Patel Urological Hospital
1st Floor, main building, Dr. V V, Petlad Rd, Yogiraj Society, Nadiad, Gujarat - 387001, India.
Kheda GUJARAT
9825316112
abhijit@mpuh.org
Dr Raja Ramchandran
Post graduate Institute of medical Education and Research
Department of Nephrology, Ground Floor , C-Block, Nehru Hospital, Sector- 12, Chandigarh - 160012, India. Chandigarh CHANDIGARH
9216958874
drraja980@gmail.com
Dr Dhananjai Agrawal
S.M.S Medical College Hospital
Room No. 507, 5th floor, Department of Nephrology,S.M.S Superspeciality Hospital, Attached to S.M.S medical college, Vivekanand Marg, C-Scheme-302001, Jaipur, Rajasthan, India. Jaipur RAJASTHAN
9414459790
dhananjaynephro@gmail.com
Dr Manas Ranjan Patel
Sanjay Gandhi Post graduate Institute of Medical Sciences
12 patients at 3mg SNP-ACTH Gel sc injection 3 times per week
SNP-ACTH (1-39) Gel administered subcutaneously.
Phase 3 a:
Dose:- 3mg
Frequency:- 3 times per week
Route:- Subcutaneous
Intervention
12 patients at 5mg SNP-ACTH Gel sc injection 3 times per week
SNP-ACTH (1-39) Gel administered subcutaneously.
Phase 3 a:
Dose:- 5mg
Frequency:- 3 times per week
Route:- Subcutaneous
Comparator Agent
1g IV infusions of rituximab on Days 0, 15, 180, 195 (Total 4 g of rituximab)
Rituximab 1 g Intravenous Injection to be administered
Intervention
SNP-ACTH (1-39) Gel treatment at the dose level determined in the Phase 3a.
SNP-ACTH (1-39) Gel administered subcutaneously.
Dose:- to be decided based on 3a study
Frequency:- 3 times per week
Route:- Subcutaneous
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
To be eligible for the study, an individual must meet all the following criteria:
1. ≥ 18 years old
2. Biopsy-proven membranous glomerulonephritis or a diagnosis of MN and a positive anti PLA2R antibody test.
3. Patients classified to be at a High Risk for progressive loss of kidney function, as defined by KDIGO 2021-Glomerular Diseases Guideline
a. eGFR of <60 mL/min/1.73 m2 and/or proteinuria >8 g/d for >6 months or
b. Normal eGFR, proteinuria >3.5 g/d and no decrease >50% after 6 months of conservative therapy with ACEi / ARB and at least one of the following: PLA2R antibody levels >50 RU/ml, serum albumin <25 g/L, urinary α1-microglobin >40 µg/min, urinary β2-microglobin > 250 mg/d
c. Patient meeting above criteria as per PI discretion as High Risk Patient.
4. eGFR by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula ≥40 mL/min/1.73 m2
5. Stable dose of blood pressure (BP) medication for at least 1 month
6. Prophylactic anticoagulation should be employed in patients when the risk of thromboembolism exceeds the estimated patient-specific risks of an anticoagulation
7. Life expectancy > 24 months
8. Vaccinated for coronavirus disease 2019 (Covid-19) before randomization.
9. Vision sufficient to measure a syringe volume or a caretaker who can do the same.
10. Patients who have had CR (Complete Remission) or PR (Partial Remission) in response to immunosuppressive therapy, however if relapsed can participate in the study if they have received high dose glucocorticoids, calcineurin inhibitors, mycophenolate Mofetil (MMF) for more than 3 months since their last dose.
11. Patients who have had CR or PR in response to immunosuppressive therapy, however if relapsed can participate in the study if they have received chlorambucil or CYC (cyclophosphamide) more than 6 months since their last dose.
12. 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.
13. If all Inclusion Points are met but patient has not been on a stable dose of ACEi (angiotensin-converting enzyme inhibitor ) or ARB (angiotensin receptor blocker ) for 90 days, he/she will be asked to return for screening once the dose of ACEi or ARB has not changed in 90 days.
ExclusionCriteria
Details
An individual who meets any of the following criteria will not be enrolled in the study:
1. Secondary membranous nephropathy as defined by history, physical exam, kidney biopsy results or serologies.
2. A confirmed diagnosis of diabetes.
3. Patient with fasting blood glucose >126 mg/dL hemoglobin A1C will be tested, If the A1C level is > 6.5% and the patient will be excluded
4. Renal biopsy showing glomerular disease other than MN or clinical manifestations, history, serology, or biopsy findings
5. Patients who have had a 50% or greater decrease in their baseline proteinuria levels within the last year in the absence of IS or cytotoxic therapy
6. Patients who have had a ≥ 50% reduction in serum titers of PLA2R (phospholipase A2 receptor) auto-antibody within 1 year before screening.
7. Patients who were non responders to previous IS treatments
8. Patients who must be initiated on drugs likely to affect renal function
9. Blood serologies suggestive of lupus nephritis or glomerular diseases other than PMN.
10. Pregnancy as determined by serum quantitative human chorionic gonadotropin (hCG) level.
11. Active infectious disease either clinically or, serologically, or culture based.
12. Patients with active hepatitis.
13. Past clinical history of Hepatitis B without anti-HBs antibodies.
14. Chronic Hepatitis C (HCV) with no successful virologic curative therapy.
15. Inability to give informed consent in the absence of a legal surrogate
16. History of cancer in remission for < 3 years excluding basal cell skin cancer and squamous cell skin cancer under surveillance by a dermatologist.
17. Scleroderma
18. Osteoporosis
19. Latent tuberculosis or tuberculin positivity as shown by the QuantiFERON Gold test.
20. Ocular herpes simplex present or history thereof.
21. Surgery within 1 month of study entry.
22. Uncompensated congestive heart failure
23. History of sensitivity to proteins of porcine origin.
24. Myasthenia gravis
25. Untreated hypothyroidism
26. Clinical liver disease diagnosed by a health care provider by signs and symptoms or biochemical liver disease manifest
27. Hemoglobinopathies including sickle cell disease.
determine the optimal dose that will be used in the Phase 3b part of the study. study will enroll 24 patients randomized to 2 different dose levels for up to 12 months. Dose levels will be: 12 patients at 3 mg SNP-ACTH Gel sc injection 3 times per week
12 patients at 5 mg SNP-ACTH Gel sc injection 3 times per week
Phase 3 b - To assess the efficacy of SNP-ACTH (1-39) Gel relative to rituximab in inducing a CR of proteinuria at month 12 and confirming durability of CR at month 24.
Phase 3 a - 13.5 month
Phase 3 b - 24 month
Secondary Outcome
Outcome
TimePoints
1. To demonstrate the safety and tolerability of SNP-ACTH (1-39) Gel.
2. To assess the efficacy of SNP-ACTH (1-39) Gel relative to rituximab in inducing a CR or PR of proteinuria at month 12.
3. To assess the efficacy of SNP-ACTH (1-39) Gel relative to rituximab in achieving immunological response at month 12.
4. To assess the utility of anti-PLA2R (or anti-THSD7A) auto-antibody levels and their relation to therapy and proteinuria at baseline.
5. To assess the clinical response to treatment by analyzing eGFR with proteinuria and auto-antibody levels (if applicable).
6. To assess the clinical response to treatment by analyzing quantitation of B and T cell subsets and their relation to therapy and proteinuria at baseline.
Total Sample Size="156" Sample Size from India="71" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This head-to-head, open-label, 2-phase superiority trial compares SNP-ACTH (1-39) Gel to rituximab in treatment of PMN that commences with an adaptive trial design for dose finding. The trial will be divided into two parts: Phase 3a and Phase 3b.
Dose finding Phase 3a part of the study will enroll 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 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.
This is an open label adaptive trial. Patients who have been randomized to SNP-ACTH (1-39) Gel who have not demonstrated an improvement in proteinuria levels or anti-PLA2R antibody levels (if applicable) after 4 months of treatment, could, at the option of the treating physician, be removed from the trial and provided an alternative treatment.
The number of randomized patients in the Phase 3b (N=132) was determined by the estimated CR rates of patients after the 12-month treatment period (45% for SNP-ACTH (1-39) Gel vs 18% for rituximab), where the durability of CR is confirmed at month 24 (12-month treatment period plus, for those patients achieving a CR at month 12, a 12-month follow up period to confirm durability of response).