Visionary Study: Phase 3 Trial of Sibeprenlimab in Immunoglobulin A Nephropathy (IgAN)

Phase 3

Active, not recruiting

• Conditions: Immunoglobulin A Nephropathy
• Interventions: Drug: Sibeprenlimab 400 mg; Drug: Placebo

• Registration Number: NCT05248646
• Lead Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Brief Summary

This is a phase 3 study to evaluate effects on proteinuria and glomerular filtration rate of sibeprenlimab 400 mg subcutaneously (s.c.) Q 4 weeks in adults with IgAN who are receiving maximally tolerated standard-of-care therapy.

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of sibeprenlimab 400 mg administered SC Q 4 weeks compared to placebo in patients with IgAN. The primary objective is to compare the relative change from baseline in the urinary protein to creatinine ratio (uPCR) in 24-hour urine collections, after 9 months of treatment. The key secondary objective is to compare the annualized rate of change from baseline (slope) of estimated glomerular filtration rate (eGFR) after approximately 24 months of treatment. There will be one main cohort comprised of approximately 450 subjects with source-verified biopsy-confirmed IgAN and eGFR ≥ 30 mL/min/1.73 m\^2. An additional exploratory cohort will be comprised of up to 20 subjects with source-verified biopsy confirmed IgAN and eGFR of 20 to \< 30 mL/min/1.73 m\^2.

Study Timeline

• Study First Submitted: 2022-02-18
• Study First Submitted QC: 2022-02-18
• Study First Posted: 2022-02-21
• Study Start: 2022-03-15
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-22
• Last Update Posted: 2024-03-26
• Primary Completion: 2026-12-30
• Study Completion: 2026-12-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 530

Inclusion Criteria

• Male and female patients ≥ 18 years of age .
• Biopsy-confirmed IgAN. (Patients with an eGFR of 30 to 45 mL/min/1.73m2 must have had a kidney biopsy performed within 36 months of the screening visit).
• Stable and maximally tolerated dose of ACEI and/or ARB for at least 3 months prior to screening. Patients who are on a stable dose of SGLT2i may participate if treatment was initiated ≥3 months prior to screening. Patients who are unable to take an ACEI or ARB may participate if their overall management conforms with standards of care and other protocol requirements.
• Screening urine protein/creatinine ratio (uPCR) ≥ 0.75 g/g or urine protein ≥ 1.0 g/day
• eGFR ≥ 30 mL/min/1.73 m2, (for the exploratory cohort only: eGFR 20- <30 mL/min/1.73 m2), calculated using the CKD-EPI equation.)

Exclusion Criteria

• Secondary forms of IgAN or IgA vasculitis.
• Coexisting chronic kidney disease other than IgAN.
• Kidney biopsy findings in addition to IgAN including those of diabetic nephropathy, membranous nephropathy, or lupus nephritis. Hypertensive vascular changes are acceptable.
• Kidney biopsy MEST or MEST-C score of T2 or C2 (Oxford IgAN classification). If MEST-scoring was not performed, the presence of > 50% tubulo-interstitial fibrosis, or crescents in > 25% of glomeruli is exclusionary. This does not apply to the exploratory cohort.
• Nephrotic syndrome
• Serum IgG < 600 mg/dL at screening.
• Chronic systemic immunosuppression, including glucocorticoids, within 16 weeks of randomization
• Participation in another interventional clinical trial and receipt of another investigational drug within 30 days prior to the administration of IMP or 5 half-lives from last investigational drug administration, whichever is longer.
• Chronic infectious disease, or acute infectious disease at time of screening.
• Type 1 diabetes, or poorly controlled Type 2 diabetes
• Uncontrolled hypertension

The protocol provides additional information about these and other inclusion and exclusion criteria.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sibeprenlimab 400 mg s.c. q 4weeks	Sibeprenlimab 400 mg	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Urinary protein to creatinine ratio (uPCR) in a 24-hour collection	At 9 months

Secondary Outcome Measures

Name	Time	Method
Annualized slope of eGFR	Over 12 months
Annualized rate of change from baseline (slope) of eGFR	Over 24 months
Proportion of subjects achieving urine total protein < 1.0 g/day and ≥ 25% reduction from baseline.	At 12 months

Trial Locations

Locations (1)

For additional information regarding sites, contact 844-687-8522; 🇺🇸 New York, New York, United States