A Phase 3, Open-label, Single-arm, Repeat-dose Trial to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Sibeprenlimab Administered Subcutaneously in Children and Adolescents With Immunoglobulin A Nephropathy

This Phase 3, open-label study will evaluate the efficacy, safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of sibeprenlimab administered subcutaneously every 4 weeks in pediatric participants aged 2 to 17 years with IgA nephropathy (IgAN). Sibeprenlimab will be administered as an add-on to standard of care therapy consisting of angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs).

CT.gov Identifier

NCT07770815

EudraCT Identifier

N/A

CTIS:

N/A

Collaborator

Otsuka Holdings/Otsuka Pharmaceutical/Korea Otsuka Pharmaceutical

Study Contact Information

N/A

Recruiting

Study Details

Diseases

IgA nephropathy

Study Drug

Sibeprenlimab

Sodium glucose co-transporter 2, unspecified

Angiotensin receptor blockers

Undisclosed - ACE inhibitor

Genes

N/A

Study Dates

Aug 2026 - Dec 2029

Sex

Female & Male

Age

2 - 17 Years

Inclusion and Exclusion Criteria

Inclusion Criteria:

Source-verified, biopsy-confirmed IgA nephropathy (IgAN).Receiving a stable and maximally tolerated dose of authorized angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) for at least 12 weeks.Participants receiving a stable dose of sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy for IgAN, if available, in addition to ACEIs and/or ARBs, must have initiated SGLT2i treatment for at least 12 weeks.Participants must have a urine protein/creatinine ratio (uPCR) ≥ 0.75 grams per gram (g/g), as measured from the geometric mean of 3 first void spot urine samples (collected within the screening window prior to Dose 1).Estimated glomerular filtration rate (eGFR) ≥ 30 milliliters per minute per 1.73 square meters (mL/min/1.73 m^2).No evidence of coexisting chronic kidney disease other than IgAN.Serum immunoglobulin G (IgG) ≥ 600 mg/dL at screening.Kidney biopsy findings not demonstrating additional pathological features inconsistent with IgAN.

Exclusion Criteria:

1) Participant has evidence of additional pathologic findings in the kidney biopsy that are consistent with an alternative etiology of kidney disease (ie, lupus nephritis, membranous nephropathy).
2) The participant's proteinuria trend should not be improving prior to enrollment. When a uPCR value reduces by more than 40% compared to previous uPCR measurements obtained in screening, at least 1 additional first void uPCR measurement must be obtained to assess if the proteinuria trend is improving.
3) Participant has kidney biopsy MEST or MEST-C score of T2 or C2; presence of > 50% tubulo-interstitial fibrosis; or crescents in > 25% of glomeruli if MEST scoring was not performed.
4) Participant has a screening serum IgG value < 600 mg/dL.
5) Participant has coexisting chronic kidney disease other than IgA nephropathy. Participant has secondary forms of IgAN as determined by the investigator (eg, infection-associated IgAN, IgA Vasculitis).
6) Participant has Type 1 diabetes or Type 2 diabetes.
7) Participant has an acute infectious disease process at the time of screening. Note: Enrollment can be considered if the acute infection has resolved within the screening window; defined as resolution of acute clinical signs, symptoms, and related clinical laboratory parameters.
8) Participant has received an organ, hematopoietic stem cell, or bone marrow transplant.
9) Participant has used any B-cell depleting therapy in the past 12 months prior to the first screening urine protein-creatinine ratio (uPCR) collection.
10) Participant has recently started nonimmunosuppressant background therapy (ie, SGLT2 inhibitor [should it become available], glucagon-like peptide 1 [GLP-1] receptor agonist, mineralocorticoid receptor antagonist, endothelin receptor antagonist). Participants are eligible if they have been on a stable dose for at least 12 weeks prior to the first screening uPCR collection.
11) Participant has used targeted release budesonide in the last 12 months prior to the first screening uPCR collection.
12) Participant has used any systemic steroids (ie, prednisone, prednisolone, methylprednisolone) or immunosuppressant therapies (for example, but not limited to: purine synthesis inhibitors, calcineurin inhibitors) in the past 16 weeks prior to the first screening uPCR collection. Inhaled, intranasal, topical, or intraocular therapies are permitted.
13) Participant has uncontrolled hypertension, defined as systolic blood pressure >= 130 mmHg and diastolic blood pressure >= 80 mmHg for participants aged 13 years and older. For participants under 13 years of age, uncontrolled hypertension is defined as systolic and diastolic blood pressures greater than the 95th percentile for age, gender, and height based on the 2017 Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents.
14) Participant has a history of nephrotic syndrome, infection-associated glomerular nephritis, liver cirrhosis, or portal hypertension.
15) Participant has a history or current evidence of a serious and/or unstable cardiovascular, hepatic, respiratory, gastrointestinal, hematologic, autoimmune, blood dyscrasias, malignancy or other medical disorder, including psychiatric disorders.
16) Participant has a 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.
17) Participant has a recent history (ie, within the past 12 months) of alcohol or drug/chemical abuse that would, based on the investigator's clinical judgment, interfere with the participant's ability to participate in the trial.
18) Participant is planning or scheduled to undergo a tonsillectomy within the time the participant would be enrolled in the trial. Prior tonsillectomy is acceptable if greater than 6 months prior to screening.
19) Participant is likely to require prohibited concomitant therapy during the trial.
20) Participant is of childbearing potential (POCBP) and is breast-feeding or has a positive pregnancy test result prior to receiving IMP.
21) Participant is of reproductive potential (PORP)/ POCBP and they or their parents/legal guardians do not agree that the participant will practice 2 different effective/highly effective methods of birth control or remain fully abstinent from sexual activity with the potential for conception, per the guidelines.
22) Participant has any chronic infectious disease (eg, chronic urinary tract infection; chronic sinusitis; active pulmonary or systemic tuberculosis; chronic viral hepatitis, such as hepatitis C or hepatitis B [defined as positive for hepatitis B surface antigen]; or human immunodeficiency virus [HIV] infection).
[NOTE] IgAN: immunoglobulin a nephropathy; IMP: investigational medicinal product; MEST: mesangial cellularity, endocapillary proliferation, segmental sclerosis, tubular atrophy; MEST-C: mesangial cellularity, endocapillary proliferation, segmental sclerosis, tubular atrophy-crescents; SGLT2i: sodium-glucose cotransporter-2 inhibitor; uPCR: urine protein-creatinine ratio

Protocol Summary

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