A Study to Evaluate the Efficacy and Safety of RO7434656 in Participants With Primary Immunoglobulin A (IgA) Nephropathy at High Risk of Progression (IMAGINATION)
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| ClinicalTrials.gov Identifier: NCT05797610 |
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Recruitment Status :
Recruiting
First Posted : April 4, 2023
Last Update Posted : April 11, 2024
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Sponsor:
Hoffmann-La Roche
Information provided by (Responsible Party):
Hoffmann-La Roche
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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 |
|---|---|---|
| Primary IgA Nephropathy | Drug: RO7434656 Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 428 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of RO7434656, an Antisense Inhibitor of Complement Factor B, in Patients With Primary IgA Nephropathy at High Risk of Progression |
| Actual Study Start Date : | August 8, 2023 |
| Estimated Primary Completion Date : | September 30, 2026 |
| Estimated Study Completion Date : | September 30, 2030 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Kidney Diseases
| Arm | Intervention/treatment |
|---|---|
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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 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.
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Drug: RO7434656
RO7434656 will be administered subcutaneously per schedule as specified. |
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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 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.
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Drug: Placebo
Matching placebo will be administered subcutaneously per schedule as specified. |
Primary Outcome Measures :
- Change From Baseline in the Urine Protein-to-Creatinine Ratio (UPCR) at Week 37 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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% or a sustained eGFR <15 mL/min/1.73m^ 2 over at least 4 weeks (both eGFR criteria 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 [ Time Frame: 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.
- Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to approximately 7 years ]
- Plasma Concentration of RO7434656 [ Time Frame: Up to approximately 7 years ]
Other Outcome Measures:
- Change From Baseline in Symptoms and Health-Related Quality of Life at Week 105 as Assessed Using the RAND Kidney Disease and Quality of Life 36-Item (KDQOL-36) Short Form [ Time Frame: Baseline, Week 105 ]The RAND KDQOL-36 is an abbreviated questionnaire that combines the generic and disease-specific components to assess participant's health-related quality of life. This 36-item questionnaire includes the RAND 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05797610
Contacts
| Contact: WA43966 https://forpatients.roche.com/ | 888-662-6728 (U.S. Only) | global-roche-genentech-trials@gene.com |
Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
| Study Director: | Clinical Trials | Hoffmann-La Roche |
| Responsible Party: | Hoffmann-La Roche |
| ClinicalTrials.gov Identifier: | NCT05797610 |
| Other Study ID Numbers: |
WA43966 2022-502102-32-00 ( Other Identifier: EU Clinical Trial Number ) |
| First Posted: | April 4, 2023 Key Record Dates |
| Last Update Posted: | April 11, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm). |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Kidney Diseases Glomerulonephritis, IGA Urologic Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases |
Male Urogenital Diseases Glomerulonephritis Nephritis Autoimmune Diseases Immune System Diseases |