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

• ClinicalTrials.gov Identifier: NCT05248646
• Recruitment Status: Recruiting
• First Posted: February 21, 2022
• Last Update Posted: March 10, 2023
• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Information provided by (Responsible Party): Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Immunoglobulin A Nephropathy	Drug: Sibeprenlimab 400 mg; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 470 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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.
• Actual Study Start Date: March 15, 2022
• Estimated Primary Completion Date: December 30, 2026
• Estimated Study Completion Date: December 30, 2026

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Sibeprenlimab 400 mg s.c. q 4weeks	Drug: Sibeprenlimab 400 mg; Sibeprenlimab 400 mg s.c. q 4 weeks; Other Name: VIS649
Placebo Comparator: Placebo	Drug: Placebo; Placebo s.c. q 4 weeks

Outcome Measures

Primary Outcome Measures :

1. Urinary protein to creatinine ratio (uPCR) in a 24-hour collection [ Time Frame: At 9 months ]

Secondary Outcome Measures :

1. Annualized rate of change from baseline (slope) of eGFR [ Time Frame: Over 24 months ]
2. Proportion of subjects achieving urine total protein < 1.0 g/day and ≥ 25% reduction from baseline. [ Time Frame: At 12 months ]
3. Annualized slope of eGFR [ Time Frame: Over 12 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Otsuka Call Center; 844-687-8522; OtsukaUS@druginfo.com

Locations

United States, New York

For additional information regarding sites, contact 844-687-8522; Recruiting

New York, New York, United States, 10001

Sponsors and Collaborators

Otsuka Pharmaceutical Development & Commercialization, Inc.

More Information

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT05248646
• Other Study ID Numbers: 417-201-00007
• First Posted: February 21, 2022
• Last Update Posted: March 10, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
• URL: https://clinical-trials.otsuka.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

IgAN; Sibeprenlimab; VIS649

Additional relevant MeSH terms:

Kidney Diseases; Glomerulonephritis, IGA; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Glomerulonephritis; Nephritis; Autoimmune Diseases; Immune System Diseases