A Study to Evaluate the Efficacy and Safety of RO7434656 in Participants With Primary Immunoglobulin A (IgA) Nephropathy at High Risk of Progression (IMAGINATION)

Roche

Status and phase: Enrolling; Phase 3

Conditions: Primary IgA Nephropathy

Treatments: Drug: RO7434656; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05797610

2022-502102-32-00 (Other Identifier)

WA43966

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of RO7434656, a novel Antisense Oligonucleotide (ASO) therapy in participants with primary IgA nephropathy (IgAN) who are at high risk of progressive kidney disease despite optimized supportive care.

Enrollment: 428 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Primary IgAN, as evidenced by a kidney biopsy performed within 7 years prior to or during screening, without known secondary cause
• Treatment with maximum tolerated doses of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) for at least 90 days immediately prior to screening
• Urine Protein-to-Creatinine Ratio (UPCR) ≥ 1 gram per gram (g/g) or urine protein excretion ≥ 1 gram per day (g/day) (with UPCR ≥ 0.8 g/g), all measured from a 24-hour urine collection during screening obtained no longer than 60 days prior to Day 1
• eGFR ≥ 20 mL/min/1.73 m^2, as calculated by the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation (Inker et al. 2021a)
• Female participants of childbearing potential must use adequate contraception

Exclusion criteria

• Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 12 weeks after the final dose of RO7434656
• Histopathologic or other evidence of another autoimmune glomerular disease
• Presence of ≥ 50% crescents on kidney biopsy, sustained doubling of serum creatinine within 3 months prior to screening, or rapidly progressive glomerulonephritis in the opinion of the investigator
• Glycated Hemoglobin (HbA1c) ≥ 6.5% or a clinical diagnosis of diabetes mellitus of any type
• Uncontrolled blood pressure, in the investigator's assessment, for 3 months prior to screening or during screening
• Use of endothelin receptor antagonists, except those approved for use in IgAN
• Initiation of mineralocorticoid receptor antagonists or endothelin receptor antagonists within 90 days prior to screening or during screening
• Previous treatment with RO7434656
• Use of herbal therapies within 90 days prior to or during screening
• Treatment with oral or intravenous (IV) corticosteroids with a dose equivalent to ≥ 7.5 milligrams per day (mg/day) of prednisone for 7 days or equivalent to ≥ 5 mg/day of prednisone for 14 days within 90 days prior to screening
• Treatment with other immunomodulatory agents within 6 months of randomization including, but not limited to, complement inhibitors, alkylating agents (e.g., cyclophosphamide or chlorambucil), or mycophenolate
• Treatment with a calcineurin inhibitor within 2 months prior to screening or during screening
• Treatment with anti-CD20 therapy within 9 months of screening or during screening
• Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in and completion of the study
• Planned major procedure or major surgery during screening or the study

Other protocol-defined inclusion/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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428 participants in 2 patient groups, including a placebo group

RO7434656

Experimental group

Description:

Participants will receive subcutaneous (SC) doses of RO7434656 on Days 1, 15, and 29 followed by once every 4 weeks until Week 105. After Week 105, participants may continue blinded treatment or enter open-label treatment until up to 1 year after the date at which the last participant completes the Week 105 assessment, withdraws, or is discontinued from the study.

Treatment:

Drug: RO7434656

Placebo

Placebo Comparator group

Description:

Participants will receive SC doses of RO7434656 matching placebo on Days 1, 15, and 29 followed by once every 4 weeks until Week 105. After Week 105, participants may continue blinded treatment or enter open-label treatment until up to 1 year after the date at which the last participant completes the Week 105 assessment, withdraws, or is discontinued from the study.

Treatment:

Drug: Placebo