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

Official title

A Phase 2/3, Multicenter, Open-label Trial to Evaluate the Long-term Safety, Tolerability, and Efficacy of Sibeprenlimab Administered Subcutaneously in Subjects With Immunoglobulin A Nephropathy.

Overview

To evaluate the long-term safety and tolerability of sibeprenlimab in subjects with IgAN

Detailed description

This is a phase 2/3, multicenter, open-label trial to evaluate the long-term safety, tolerability, and efficacy of sibeprenlimab administered subcutaneously (SC) to subjects with IgAN.

Eligible subjects will have participated in trials 417-201-00007 or VIS649-201 and, in the investigator's judgement, could benefit from continued treatment with sibeprenlimab.

Interventions

• Drug Sibeprenlimab 400 mg s.c. Q4weeks
  Sibeprenlimab 400 mg s.c. q 4 weeks

Primary outcome measures

• Adverse Events [Time frame: From baseline to the end-of-trial visit in Week 112.]

Secondary outcome measures (4)

• Annualized slope of Estimated Glomerular Filtration Rate (eGFR) [Time frame: Over 12 and 24 months]
• Urine protein/creatinine ratio (uPCR) in a 24-hour collection [Time frame: At 12 and 24 months]
• Proportion of Subjects with Clinical Remission as defined in the protocol [Time frame: At 12 and 24 months]
• Time to Progression of Chronic Kidney Disease, as defined in the protocol [Time frame: Over 24 months]

Eligibility criteria

Inclusion criteria

• Subjects who completed Trial 417-201-00007 (at least 20 of the 26 doses over a 2-year duration and the end-of-trial visit) or Trial VIS649-201 (at least 9 of the 12 doses over a 1-year duration and the end-of-trial visit) without safety concerns and who, in the opinion of the investigator, could potentially benefit from treatment with sibeprenlimab for IgAN.
• Ability to provide written, informed consent prior to initiation of any trial-specific procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial.

Exclusion criteria

• Subjects who have not completed participation in Trials 417-201-00007 or VIS649-201.
• Subjects with treatment-limiting AEs during Trials 417-201-00007 or VIS649-201 considered related to IMP per investigator judgement.
• Noncompliance, due to subject's repeated failure to follow trial procedures during the course of their participation in Trials 417-201-00007 and VIS649-201 (eg, subjects deemed to be noncompliant with the visit schedule, trial assessments, or treatment regimen). The medical monitor should be contacted if the investigator is unsure of a subject's eligibility.
• Subjects who have a positive pregnancy test result prior to receiving IMP.
• Heterosexually active biological males or subjects of childbearing potential, or their partners, who do not agree to adhere to contraceptive requirements from the time of consent through the end of the subject's participation in the trial and an additional 90 days (biological male subjects) or 30 days (biological female subjects) thereafter.
• Biological male subjects who do not agree to avoid donation of sperm from the time of consent through the end of the subject's participation in the trial and an additional 90 days thereafter.
• Subject has nephrotic syndrome, defined for this purpose as 24-hour urine protein > 3.5 g with concurrent hypoalbuminemia (serum albumin < 2.5 g/dL), hyperlipidemia (total cholesterol > 350 mg/dL), and edema. Subjects with isolated nephrotic range proteinuria (> 3.5 g/day) will be eligible.
• Subject has a history or current evidence of a serious and/or unstable cardiovascular, respiratory, gastrointestinal, hematologic, autoimmune, rheumatologic, blood dyscrasias or other medical disorder, including psychiatric disorders, cirrhosis, or ongoing malignancy. History of minor skin cancers (not including melanoma) or surgically treated, limited cervical carcinomas (ie, carcinoma in situ) are not exclusionary.
• History of a previous hypersensitivity or severe allergic reaction with generalized urticaria, angioedema or anaphylaxis to any of the ingredients of the sibeprenlimab SC injection formulation.
• Subject has a body mass index < 16 kg/m\^2.
• Subject has received an organ transplant (ie, solid or a bone marrow or hematologic stem cell transplantation).
• Subject is currently receiving, or has received within 16 weeks prior to enrollment, systemic immunosuppressive therapy (ie, steroids such as targeted release budesonide, complement inhibitors, mycophenolate, rituximab). Note: topical, ophthalmic, rectal, intra-articular, inhaled corticosteroids, and short courses of oral/intravenous steroids (<= 14 days) are allowed.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 15 centers

• Clinical Research Site #336 — Birmingham
• Clinical Research Site #325 — Los Angeles
• Clinical Research Site #370 — Palo Alto
• Clinical Research Site #330 — Denver
• Clinical Research Site #323 — Lauderdale Lakes
• Clinical Research Site #373 — Atlanta
• Clinical Research Site #356 — Lawrenceville
• Clinical Research Site #369 — Boston
• … and 7 more centers

Japan · 15 centers

Center list to be confirmed — check the primary protocol.

India · 13 centers

• Clinical Research Site #081 — Hyderabad
• Clinical Research Site #073 — Ahmedabad
• Clinical Research Site #070 — Nadiād
• Clinical Research Site #087 — Bengaluru
• Clinical Research Site #079 — Manipal
• Clinical Research Site #071 — Kozhikode
• Clinical Research Site #074 — Thiruvananthapuram
• Clinical Research Site #084 — Pune
• … and 5 more centers

South Korea · 13 centers

Center list to be confirmed — check the primary protocol.

Australia · 9 centers

• Clinical Research Site #003 — Garran
• Clinical Research Site #013 — Concord
• Clinical Research Site #014 — Kogarah
• Clinical Research Site — New Lambton Heights
• Clinical Research Site #006 — Saint Leonards
• Clinical Research Site #012 — Adelaide
• Clinical Research Site #001 — Fitzroy
• Clinical Research Site #010 — St Albans
• … and 1 more center

China · 9 centers

• Clinical Research Site #036 — Beijing
• Clinical Research Site #020 — Beijing
• Clinical Research Site #028 — Guangzhou
• Clinical Research Site #044 — Changsha
• Clinical Research Site #030 — Wuxi
• Clinical Research Site #022 — Nanchang
• Clinical Research Site #026 — Jinan
• Clinical Research Site #038 — Chengdu
• … and 1 more center

Spain · 9 centers

Center list to be confirmed — check the primary protocol.

Brazil · 6 centers

• Clinical Research Site #820 — Recife
• Clinical Research Site #824 — Porto Alegre
• Clinical Research Site #821 — Joinville
• Clinical Research Site #822 — São José do Rio Preto
• Clinical Research Site #831 — Rio de Janeiro
• Clinical Research Site #823 — São Paulo

Malaysia · 6 centers

Center list to be confirmed — check the primary protocol.

France · 5 centers

• Clinical Research Site #433 — Grenoble
• Clinical Research Site #430 — Nîmes
• Clinical Research Site #432 — Nantes
• Clinical Research Site #439 — Limoges
• Clinical Research Site #434 — Sr Priest En Jarez

Hong Kong · 5 centers

• Clinical Research Site #064 — Hong Kong
• Clinical Research Site #060 — Hong Kong
• Clinical Research Site #061 — Hong Kong
• Clinical Research Site #062 — Kowloon
• Clinical Research Site #063 — Shatin

Taiwan · 5 centers

Center list to be confirmed — check the primary protocol.

Thailand · 5 centers

Center list to be confirmed — check the primary protocol.

Israel · 4 centers

• Clinical Research Site #494 — Ashkelon
• Tel Aviv University Sackler School of Medicine - Meir Medical Center (MMC) (Meir Hospital) — Kfar Saba
• Clinical Research Site #495 — Nahariya
• … and 1 more center

Italy · 4 centers

Center list to be confirmed — check the primary protocol.

Portugal · 4 centers

Center list to be confirmed — check the primary protocol.

Sri Lanka · 4 centers

Center list to be confirmed — check the primary protocol.

Argentina · 3 centers

• Clinical Research Site #800 — Buenos Aires
• Clinical Research Site #802 — Buenos Aires
• Clinical Research Site #801 — Córdoba

Canada · 3 centers

• Clinical Research Site #300 — Calgary
• Clinical Research Site #305 — Scarborough Village
• CISSS de la Monteregie centre-Centre de recherche Hopital Charles Lemoyne — Greenfield Park

Singapore · 3 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 3 centers

Center list to be confirmed — check the primary protocol.

Belgium · 2 centers

• Clinical Research Site #401 — Genk
• Clinical Research Site #405 — Genk

Croatia · 2 centers

• Clinical Research Site #413 — Split
• Clinical Research Site #414 — Zagreb

Germany · 2 centers

• Clinical Research Site #455 — Mainz
• Universitaetsklinikum Carl Gustav Carus — Dresden

Philippines · 2 centers

Center list to be confirmed — check the primary protocol.

Poland · 2 centers

Center list to be confirmed — check the primary protocol.

Czechia · 1 center

• Vseobecna fakultni nemocnice v Praze — Prague

Greece · 1 center

• Clinical Research Site #472 — Heraklion

Hungary · 1 center

• Clinical Research Site #482 — Pécs

Netherlands · 1 center

Center list to be confirmed — check the primary protocol.

Vietnam · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT05248659 · 417-201-00012

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗