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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

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SLCTR Registration Number

SLCTR/2022/013


Date of Registration

22 May 2022

The date of last modification

Sep 09, 2022


Trial Status



Application Summary


Scientific Title of Trial

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


Public Title of Trial

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


Disease or Health Condition(s) Studied

Immunoglobulin A Nephropathy


Scientific Acronym

VISIONARY


Public Acronym

VISIONARY


Brief title

Trial of Sibeprenlimab in the Treatment of Immunoglobulin A Nephropathy (IgAN)


Universal Trial Number

U1111-1275-6578


Any other number(s) assigned to the trial and issuing authority

ClinicalTrials.gov Identifier: NCT05248646


Trial Details


What is the research question being addressed?

What is the Efficacy and Safety of Sibeprenlimab Administered Subcutaneously in Subjects with Immunoglobulin A Nephropathy (IgAN)?


Type of study

Interventional


Study design

Allocation

Randomized controlled trial


Masking

Double blinded : Participants, Investigators, Healthcare providers


Control

Placebo


Assignment

Parallel


Purpose

Treatment


Study Phase

Phase 3


Intervention(s) planned

Study Sites • Sri Jayewardenepura General Hospital • National Hospital of Sri Lanka • National Hospital, Kandy • Kurunegala Teaching Hospital • Karapitiya Teaching Hospital

Randomization: Subjects will be randomized with equal allocation (1:1) to sibeprenlimab or placebo. Randomization will be stratified by screening urine protein/creatinine ratio (uPCR; <2.0 g/g versus > 2.0 g/g), screening estimated glomerular filtration rate (eGFR; 30 - 44 mL/min versus >45 mL/min), and sodium-glucose cotransporter-2 inhibitor (SGLT2i) use at the time of randomization (yes or no). Approximately 450 subjects will be randomized with equal allocation (1:1) to sibeprenlimab or placebo (approximately 225 subjects per treatment) in a blinded manner.

Subjects will be randomly assigned to a treatment group. The randomization code will be created by the sponsor following the standard operating procedures.

Intervention: This trial will evaluate a dose of 400 mg sibeprenlimab compared with placebo. The Investigational Medicinal Product (IMP) (sibeprenlimab or placebo) will be administered Sub Cutaneously (SC) once every 4 weeks (total of 26 doses) by trained, qualified personnel designated by the investigator or sponsor. The IMP administration will be in the abdomen, thigh, or upper arm based on assignment at randomization. For all subjects, Dose 1 (Day 1), Dose 2 (Week 4), Dose 3 (Week 8), Dose 4 (Week 12), Dose 5 (Week 16), and Dose 7 (Week 24) will be injected SC in the abdomen. Dose 6 (Week 20) and Dose 8 (Week 28) will be rotated to either the thigh or upper arm based on assignment at randomization so that each subject has at least one IMP administration in each of the SC injection sites. From Dose 9 (Week 32) and onwards, subjects will be allowed to select which injection site they prefer for the IMP administration. The date and time of IMP administration, the volume of IMP administered, and the injection site location will be recorded for each IMP administration. The details of the placebo is given below: 25 mM histidine, 100 mM sorbitol, 50 mM arginine, 50 mM glutamic acid, 0.02% (w/v) PS-80, pH 6.2

Blinding: subjects, investigators, trial staff and sponsor, will remain blinded to treatment assignment until the final analysis of the key secondary endpoint of eGFR


Inclusion criteria

• Male and female patients >18 years of age. • Biopsy-confirmed IgA Nephropathy (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 (Angiotensin-converting enzyme inhibitor) and/or ARB (Angiotensin receptor blocker) 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 (Chronic Kidney Disease Epidemiology Collaboration) equation.

*The Exploratory cohort is up to 20 subjects with IgAN and an eGFR of 20 to 30 mL/min/1.73 m2. These subjects will also randomized with equal allocation (1:1) to sibeprenlimab or placebo in this cohort.


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 (Mesangial cellularity, endocapillary proliferation, segmental sclerosis, tubular atrophy) or MEST-C (MEST-Crescents) 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 Exploratory cohort is up to 20 subjects with IgAN and an eGFR of 20 to 30 mL/min/1.73 m2. These subjects will also randomized with equal allocation (1:1) to sibeprenlimab or placebo in this cohort.



Primary outcome(s)

1.

Urinary protein to creatinine ratio (uPCR) in a 24-hour collection

[

At 9 months

]

Secondary outcome(s)

1.

Annualized rate of change from baseline (slope) of eGFR.

[

[ Over 24 months]

]
2.

Proportion of subjects achieving urine total protein < 1.0 g/day and > 25% reduction from baseline.

[

[ At 12 months]

]
3.

Annualized slope of eGFR.

[

[Over 12 months]

]
4.
[]
5.
[]

Target number/sample size

Global: 484 Sri Lanka: 20 (10 in each arm)


Countries of recruitment

Argentina, Australia, Brazil, Canada, China, Czech Republic, France, Germany, Hong Kong, India, Israel, Italy, Japan, Korea, Republic of, Malaysia, Netherlands, Philippines, Poland, Portugal, Singapore, Spain, Sri Lanka, Thailand, United Kingdom, United States, Viet Nam


Anticipated start date

2022-06-30


Anticipated end date

2026-06-12


Date of first enrollment


Date of study completion


Recruitment status

Pending


Funding source

Otsuka Pharmaceutical Development & Commercialization, Inc.


Regulatory approvals

National Medicine Regulatory Authority (NMRA) Sri Lanka- Approval Pending



State of Ethics Review Approval


Status

Approved


Date of Approval

2022-03-08


Approval number

P/01/01/2022


Details of Ethics Review Committee

Name: Ethics Review Committee
Institutional Address: Faculty of Medicine, University of Kelaniya, P.O Box 6, Thalagolla Road, Ragama, Sri Lanka
Telephone:+94 11 2961267
Email: ercmed@kln.ac.lk

Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

Dr. Chula Herath
Consultant Nephrologist
Sri Jayewardenepura General Hospital, Nugegoda – 10250, Sri Lanka

+94112778610

chulaherath@gmail.com

Contact Person for Public Queries

Dr. Chula Herath
Consultant Nephrologist
Sri Jayewardenepura General Hospital, Nugegoda – 10250, Sri Lanka

0773017025

chulaherath@gmail.com


Primary study sponsor/organization

Otsuka Pharmaceutical Development & Commercialization, Inc.

2440 Research Boulevard Rockville, Maryland 20850, United State
844-687-8522

OtsukaUS@drugunfo.com

Secondary study sponsor (If any)







Trial Completion details


Do the investigators plan to share identified individual clinical trial participant-level data (IPD)?

Yes


IPD sharing plan description

N/A


Study protocol available

No


Protocol version and date

Not Available


Protocol URL

Not Available


Results summary available

No


Date of posting results


Date of study completion


Final sample size


Date of first publication


Link to results


Brief summary of results