VISIONARY Trial: Phase 3 Trial of Sibeprenlimab in the Treatment of Immunoglobulin A Nephropathy (IgAN)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Otsuka Pharmaceutical Development And Commercialization Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13], Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

3 Nov 2022 → 13 May 2026

Decision date (initial)

2022-09-05

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Otsuka Pharmaceutical Development and Commercialization Inc.

External identifiers

EU CT number

2022-500079-30-00

ClinicalTrials.gov

NCT05248646

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Pharmacodynamic, Safety, Therapy

To compare the relative change from baseline in uPCR achieved with sibeprenlimab versus placebo added to SOC, after 9 months of SC administration.

Secondary objectives 6

1. To compare the annual rate of change from baseline (slope) of eGFR achieved with sibeprenlimab versus placebo added to SOC, after approximately 24 months of SC administration.
2. To evaluate the treatment effect of sibeprenlimab on eGFR versus placebo added to SOC.
3. To compare the treatment effects on the progression to CKF endpoint achieved with sibeprenlimab versus placebo added to SOC.
4. To evaluate the effect of sibeprenlimab on total IgA, IgG, and IgM.
5. To evaluate the safety and tolerability of sibeprenlimab versus placebo added to SOC.
6. To evaluate the immunogenicity of sibeprenlimab.

Conditions and MedDRA coding

IgA Nephropathy

Regulatory references

Scientific advice from competent authorities

Pharmaceuticals And Medical Devices Agency, Food And Drug Administration, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003085-PIP01-21

Plan to share IPD

Yes

IPD 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. 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. Otsuka will share data supported by the protocol, statistical analysis plan (SAP) and clinical study report (CSR) on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Subjects with source-verified biopsy confirmed IgAN and who are on a stable and maximally tolerated dose of authorized angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs; as per local standard of care and applicable guidelines) for at least 3 months prior to screening. Furthermore, subjects who are on a stable dose of SGLT2i therapy for IgAN, in addition to ACEIs and/or ARBs, may participate in the trial if treatment was initiated at least 3 months prior to screening. At screening, subjects must have an uPCR ≥ 0.75 g/g or urine protein ≥ 1.0 g/day, as measured from 24-hour urine samples (mean of the two 24-hour urine samples collected up to 2 weeks apart at screening), and eGFR ≥ 30 mL/min/1.73 m². Subjects with an eGFR of 30 to 44 mL/min/1.73 m² are required to have had a kidney biopsy performed within 36 months of the screening visit. For the exploratory cohort only, subjects must have an eGFR of 20 to 29 mL/min/1.73 m²

Exclusion criteria 1

1. Subjects with secondary forms of IgAN or coexisting chronic kidney disease, other than IgAN, will be excluded from participation in the trial. Subjects who have a body mass index < 16 kg/m² or a serum immunoglobulin (Ig) G value < 600 mg/dL at screening will also be excluded. In addition, subjects with a kidney biopsy showing mesangial cellularity, endocapillary proliferation, segmental sclerosis, tubular atrophy (MEST) or MEST-crescents (MEST C) score of T2 or C2 will also be excluded. Note: this criterion does not apply to the exploratory cohort

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary Efficacy: Ratio of uPCR at 9 months compared with baseline, based on 24-hour urine collection.

Secondary endpoints 6

1. The annualized slope of eGFR estimated over the course of approximately 24 months.
2. Efficacy: Mean change of eGFR from baseline at 24 months.
3. Efficacy: Progression to CKF, as assessed by: Time to progression to CKF (time from the randomization date to first occurrence of CKF); Proportion of subjects with progression to CKF.
4. Change from baseline in total serum IgA, IgG, and IgM concentration
5. Safety: Incidence of TEAEs graded by severity, clinical laboratory tests, vital sign measurements, 12 lead ECGs, physical examinations, and injection site reactions.
6. Other: Evaluation of serum ADA.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Otsuka Pharmaceutical Development And Commercialization Inc.

Sponsor organisation

Otsuka Pharmaceutical Development And Commercialization Inc.

Address

2440 Research Boulevard

City

Rockville

Postcode

20850-3238

Country

United States

Scientific contact point

Organisation

Otsuka Pharmaceutical Development And Commercialization Inc.

Contact name

EU Clinical Trials Helpdesk

Public contact point

Organisation

Otsuka Pharmaceutical Development And Commercialization Inc.

Contact name

EU Clinical Trials Helpdesk

Third parties 20

Locations

12 EU/EEA countries · 56 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 440 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

32 submissions — initial application plus substantial / non-substantial modifications