Trial of Sibeprenlimab in the Treatment of Immunoglobulin A Nephropathy

Phase 2/3

Recruiting

• Conditions: Diseases of the genitourinary system,

• Registration Number: CTRI/2024/02/062883
• Lead Sponsor: Otsuka Pharmaceutical Development Commercialization Inc

Brief Summary

This is a phase 2/3, multicenter, open-label trial to evaluate the long-term safety, tolerability, and efficacy of sibeprenlimab administered subcutaneously (SC) to subjects with IgAN.

The screening visit will take place at the trial site clinic up to 30 days prior to the first dose of investigational medicinal product (IMP). Where possible, it is recommended that assessments collected after completion of IMP administration in Trials 417-201-00007 or VIS649-201 be utilized for screening. If the 24-hour urine collection was performed within the past 3 months prior to screening, the collection does not need to be repeated at screening.

Eligible subjects will attend the screening and Day 1 visit at the trial site clinic. All other visits may be completed remotely using mobile health services per the discretion of the investigator and subject.

Sibeprenlimab will be administered as a SC injection once every 4 weeks. A total of 26 doses are planned to be administered, with Dose 1 administered on Day 1 and Dose 26 administered in Week 100. Subjects discontinuing treatment prior to Dose 26 will complete the early discontinuation visit (assessments at Week 104) at the time of treatment discontinuation and will be encouraged to complete the remainder of all planned trial visits after treatment discontinuation.

Subjects will complete a follow-up visit in Week 104. The end-of-trial visit will take place in Week 112, at which time final assessments will be performed.

Subjects will be evaluated throughout the trial for safety, efficacy, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity assessments.

Enrollment into the trial will be drawn from eligible subjects who, in the investigator’s judgement, could potentially benefit from treatment with sibeprenlimab for IgAN and will include rollover subjects from Trials 417-201-00007 and VIS649-201. Eligible subjects will include:

- Subjects who have completed at least 20 of the 26 doses and the end-of-trial visit in the phase 3, double-blind, placebo-controlled trial to evaluate the efficacy and safety of sibeprenlimab administered SC in subjects with IgAN (Trial 417-201-00007),

- Subjects who have completed at least 9 of the 12 doses and the end-of-trial visit in the phase 2, double-blind, placebo-controlled, multiple dose trial to evaluate the efficacy and safety of sibeprenlimab administered intravenously (IV) in subjects with IgAN (Trial VIS649-201).

De novo (new) subjects will not be enrolled in this trial.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-02-29
• Last Update Posted: 2025-01-27

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

• Subjects are required to meet the following inclusion criteria when assessed: 1) Subjects who completed Trial 417-201-00007 (at least 20 of the 26 doses and the end-of-trial visit) or Trial VIS649-201 (at least 9 of the 12 doses and the end-of-trial visit) without safety concerns and who, in the opinion of the investigator, could potentially benefit from treatment with sibeprenlimab for IgAN.
• 2. Subject has eGFR more than or equal to 20 mL/min/1.73 m2, calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine eGFR formula.
• 3. Ability to provide written, informed consent prior to initiation of any trial-specific procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial.

Exclusion Criteria

• 1. Subjects who have not completed participation in Trials 417-201-00007 or VIS649-201.
• 2. Subjects with treatment-limiting adverse events (AEs) during Trials 417-201-00007 or VIS649-201 considered related to IMP per investigator judgement.
• 3. Noncompliance, due to subject`s repeated failure to follow trial procedures during the course of their participation in Trials 417-201-00007 and VIS649-201 (eg, subjects deemed to be noncompliant with the visit schedule, trial assessments, or treatment regimen).
• The medical monitor should be contacted if the investigator is unsure of a subject`s eligibility.
• 4. Subjects who have a positive pregnancy test result prior to receiving IMP.
• 5. Heterosexually active biological males or subjects of childbearing potential, or their partners, who do not agree to adhere to contraceptive requirements from the time of consent through the end of the subject`s participation in the trial and an additional 90 days (biological male subjects) or 30 days (biological female subjects) thereafter.
• 6. Subjects must also agree not to donate sperm from the time of consent through the end of the subject`s participation in the trial and an additional 90 days thereafter.
• 7. Subject has nephrotic syndrome, defined for this purpose as 24-hour urine protein > 3.5 g with concurrent hypoalbuminemia (serum albumin < 2.5 g/dL), hyperlipidemia (total cholesterol > 350 mg/dL), and edema.
• 8. Subject has a history or current evidence of a serious and/or unstable cardiovascular, respiratory, gastrointestinal, hematologic, autoimmune, rheumatologic, blood dyscrasias or other medical disorder, including psychiatric disorders, cirrhosis, or ongoing malignancy.
• 9. History of a previous severe allergic reaction with generalized urticaria; angioedema or anaphylaxis.
• 10. Subject has a body mass index < 16 kg/m2.
• 11. Subject has received an organ transplant (ie, solid or a bone marrow or hematologic stem cell transplantation).
• 12. Subject is currently receiving, or has received within 16 weeks prior to enrollment, systemic immunosuppression (note: topical, ophthalmic, rectal, intra-articular, inhaled corticosteroids, and short courses of oral/intravenous steroids [less than or equal to 14 days] are allowed).
• 13. Subject has participated in another interventional clinical trial (other than Trials 417-201-00007 and VIS649-201) and received another investigational drug within 30 days prior to the administration of IMP or 5 half-lives from last investigational drug administration, whichever is longer.
• 14. Subject has any chronic infectious disease (eg, chronic urinary tract infection; chronic sinusitis; bronchiectasis; active pulmonary or systemic tuberculosis; chronic viral hepatitis, such as hepatitis C or hepatitis B [defined as positive for hepatitis B surface antigen]; or human immunodeficiency virus [HIV] infection).
• 15. Subject has acute infectious disease at the time of screening.
• 16. Subject has Type 1 diabetes.
• 17. Subject has uncontrolled Type 2 diabetes, as evidenced by a screening hemoglobin A1c (HbA1c) value > 8%.
• 18. Subject has uncontrolled hypertension (defined as systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg).
• 19. Subject who has a history of alcohol or drug/chemical abuse based on the investigator`s clinical judgement.
• 20. Subject is judged by the investigator or the medical monitor to be inappropriate for the trial.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To evaluate the long-term safety and tolerability of sibeprenlimab in subjects with IgAN.	From baseline to the end-of-trial visit in Week 112.

Secondary Outcome Measures

Name	Time	Method
Annualized slope of Estimated Glomerular Filtration Rate(eGFR)	Over 12 & 24 months
Time to Progression of Chronic Kidney Disease, as defined in the protocol	Over 24 months
Urine protein-creatinine ratio (uPCR) in a 24-hour collection	At 12 & 24 months
Proportion of Subjects with Clinical Remission as defined in the protocol	At 12 & 24 months

Trial Locations

Locations (16)

Christian Medical College & Hospital; 🇮🇳 Vellore, TAMIL NADU, India

Government Medical College, Ulloor; 🇮🇳 Thiruvananthapuram, KERALA, India

Jawaharlal Institute of Postgraduate Medical Education and Research; 🇮🇳 Pondicherry, PONDICHERRY, India

Kasturba Medical college and Hospital; 🇮🇳 Udupi, KARNATAKA, India

Kerala University of Health Sciences Government Medical College; 🇮🇳 Kozhikode, KERALA, India

Kusum Dhirajlal Hospital; 🇮🇳 Ahmadabad, GUJARAT, India

Lifepoint Multispecialty Hospital; 🇮🇳 Pune, MAHARASHTRA, India

Mahatma Gandhi Mission, MGM Medical College and Hospital; 🇮🇳 Aurangabad, MAHARASHTRA, India

MS Ramaiah Medical College Hospital; 🇮🇳 Bangalore, KARNATAKA, India

Muljibhai Patel Urological Hospital; 🇮🇳 Kheda, GUJARAT, India

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Christian Medical College & Hospital

🇮🇳Vellore, TAMIL NADU, India

Dr Suceena Alexander

Principal investigator

9894519136

suceena@gmail.com