Clinical trial NCT05248646: Visionary Study: Phase 3 Trial of Sibeprenlimab in Immunoglobulin A Nephropathy (IgAN)
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Sibeprenlimab Administered Subcutaneously in Subjects With Immunoglobulin A Nephropathy.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Immunoglobulin A Nephropathy
Keywords: IgAN
Sibeprenlimab
VIS649
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-21
Enrollment: 530
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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Urinary protein to creatinine ratio (uPCR) in a 24-hour collection
timeFrame: At 9 months
Secondary outcomes:
measure: Annualized rate of change from baseline (slope) of eGFR
timeFrame: Over 24 months
measure: Proportion of subjects achieving urine total protein < 1.0 g/day and ≥ 25% reduction from baseline.
timeFrame: At 12 months
measure: Annualized slope of eGFR
timeFrame: Over 12 months
Other outcomes:
Locations:
city: New York
country: United States
facility: For additional information regarding sites, contact 844-687-8522
state: New York
Study officials:
References: