IMAGINATION: A Study to Evaluate the Efficacy and Safety of RO7434656 in Participants With Primary Immunoglobulin A (IgA) Nephropathy at High Risk of Progression
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: RO7434656 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 up to 1 year after the date at which the last participant completes the Week 105 assessment, withdraws, or is discontinued from the study. |
Drug: RO7434656
RO7434656 will be administered subcutaneously per schedule as specified.
|
| Placebo Comparator: Placebo 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 up to 1 year after the date at which the last participant completes the Week 105 assessment, withdraws, or is discontinued from the study. |
Drug: Placebo
Matching placebo will be administered subcutaneously per schedule as specified.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in the Urine Protein-to-Creatinine Ratio (UPCR) at Week 37 [Baseline, Week 37]
UPCR will be assessed in urine sampled over 24 hours.
Secondary Outcome Measures
- Estimated Glomerular Filtration Rate (eGFR) Slope at Week 105 from Baseline [Baseline, Week 105]
eGFR will be calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation.
- Time to the Composite Kidney Failure Endpoint [Up to approximately 7 years]
Time to the composite kidney failure endpoint is defined as receipt of kidney transplantation, need for kidney replacement therapy, or a sustained decline in eGFR of ≥ 30% (requires two consecutive central laboratory eGFR values meeting criteria ≥ 4 weeks apart), whichever occurs first, without the receipt of other immunosuppressive or background therapies for the treatment of IgAN.
- Change From Baseline in Fatigue at Week 105 [Baseline, Week 105]
Fatigue will be assessed with the Functional Assessment of Chronic Illness Therapy-Fatigue subscale (FACIT-F). The FACIT-F Scale is a 13-item scale used to measure self-reported fatigue. Items are assessed on a 5-point Likert scale, with responses ranging from 0 for "not at all" to 4 for "very much". The total raw score is the sum of the values of each scored question and ranges from 0 to 52. A higher score indicates less fatigue.
- Change From Baseline in Symptoms and Health-Related Quality of Life at Week 105 as Assessed Using the Kidney Disease and Quality of Life 36-Item (KDQOL-36) Short Form [Baseline, Week 105]
The KDQOL-36 is an abbreviated questionnaire that combines generic and disease-specific components to assess participant's health-related quality of life. This 36-item questionnaire includes the Short Form 12 (SF-12), Version 1 (12 items) and 3 disease-related domains, symptoms/problems (12 items), burden of kidney disease (4 items), and effects of kidney disease (8 items). It uses a recall of 4 weeks, and items are assessed on 3- to 5-point Likert scales or with a dichotomous response option. Higher score indicates better health. The raw scores are transformed linearly to a range of 0 to 100, with higher scores indicating better health.
- Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs) [Up to approximately 7 years]
- Plasma Concentration of RO7434656 [Up to approximately 7 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Primary IgAN, as evidenced by a kidney biopsy performed within 7 years prior to or during screening, without known secondary cause
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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
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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
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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)
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Female participants of childbearing potential must use adequate contraception
Exclusion Criteria:
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Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 12 weeks after the final dose of RO7434656
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Histopathologic or other evidence of another autoimmune glomerular disease
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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
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Glycated Hemoglobin (HbA1c) ≥ 6.5% or a clinical diagnosis of diabetes mellitus of any type
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Uncontrolled blood pressure, in the investigator's assessment, for 3 months prior to screening or during screening
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Use of endothelin receptor antagonists, except those approved for use in IgAN
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Initiation of mineralocorticoid receptor antagonists or endothelin receptor antagonists within 90 days prior to screening or during screening
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Previous treatment with RO7434656
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Use of herbal therapies within 90 days prior to or during screening
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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
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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
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Treatment with a calcineurin inhibitor within 2 months prior to screening or during screening
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Treatment with anti-CD20 therapy within 9 months of screening or during screening
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Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in and completion of the study
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Planned major procedure or major surgery during screening or the study
Other protocol-defined inclusion/exclusion criteria may apply
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- WA43966
- 2022-502102-32-00