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

JRCT ID: jRCT2061230087

Registered date:09/01/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Immunoglobulin A nephropathy
• Date of first enrollment: 13/05/2024
• Target sample size: 428
• Countries of recruitment: USA,Japan,Poland,Japan,Spain,Japan,France,Japan,Singapore,Japan,Argentina,Japan,Australia,Japan,Brazil,Japan,China,Japan,Germany,Japan,Italy,Japan,Taiwan,Japan
• Study type: Interventional
• Intervention(s): RO7434656: SC doses of either 70 mg of RO7434656 or matching volume of placebo on Days 1, 15, and 29, followed by once every 4 weeks

Outcome(s)

Primary Outcome

efficacy
Change in proteinuria, as measured by the UPCR change at Week 37 from baseline from a 24-hour collection

Secondary Outcome

efficacy: Estimated eGFR slope at Week 105 from baseline
efficacy: Time to the composite kidney failure endpoint
efficacy: Change in fatigue at Week 105 compared with baseline
safety: Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs)
phamacokinetics: Plasma Concentration of RO7434656

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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

Exclude 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

Related Information

• Primary Sponsor: Nikhil Kamath
• Secondary ID(s): NCT05797610