A Study to Evaluate the Efficacy and Safety of Sefaxersen (RO7434656) in Participants With Primary Immunoglobulin A (IgA) Nephropathy at High Risk of Progression
Purpose
The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of sefaxersen (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
- Primary IgA Nephropathy
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Primary IgAN, as evidenced by a kidney biopsy performed within 10 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, except for interruptions due to illness (not greater than 7 consecutive days), unless the potential participant is intolerant to these medications - 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 - 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) - Vaccination against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae according to national vaccination recommendations - 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 sefaxersen - 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 - History of kidney transplantation - Glycated Hemoglobin (HbA1c) ≥ 6.5% or a clinical diagnosis of diabetes mellitus of any type - Systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg from the average of two measurements performed at least 1 minute apart during screening - Initiation of SGLT2 inhibitors within 16 weeks prior to screening or during screening - Initiation of endothelin receptor antagonists within 90 days prior to screening or during screening - Initiation of mineralocorticoid receptor antagonists or non-dihydropyridine calcium channel blockers within 90 days prior to screening or during screening - Use of herbal therapies within 90 days prior to or during screening - Treatment with investigational therapy within 28 days prior to screening or 5.5 drug-elimination half-lives of that investigational product prior to screening - Treatment with an investigational therapy planned during the treatment period - Previous treatment with sefaxersen - 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 corticosteroids with systemic effects during screening - Treatment with a systemic calcineurin inhibitor within 2 months prior to screening or during screening - Treatment with anti-CD20 therapy within 9 months of screening or during screening - Treatment with other systemic immunosuppressive agents within 6 months of randomization including, but not limited to, complement inhibitors, alkylating agents (e.g., cyclophosphamide or chlorambucil), azathioprine, or mycophenolate - Planned major procedure or major surgery during screening or the study - Substance abuse within 12 months prior to 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 - History of malignancy within < 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death - Usage of GLP-1-based therapy (i.e., GLP-1 mono-agonists, GLP-1/GIP dual agonists, etc.) within 90 days prior to screening or during screening, or intent to initiate during the study period
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental sefaxersen (RO7434656) |
Participants will receive subcutaneous (SC) doses of sefaxersen (RO7434656) on Days 1, 15, and 29 followed by once every 4 weeks until Week 105. Participants may be eligible to switch to open-label treatment after Week 105 at the investigator's discretion until up to 1 year after the common-close timepoint, the date when the last participant completes the Week 105 assessment, withdraws, or is discontinued from the study. |
|
|
Placebo Comparator Placebo |
Participants will receive SC doses of sefaxersen (RO7434656) matching placebo on Days 1, 15, and 29 followed by once every 4 weeks until Week 105. Participants may be eligible to switch to open-label treatment after Week 105 at the investigator's discretion until up to 1 year after the common-close timepoint, the date when the last participant completes the Week 105 assessment, withdraws, or is discontinued from the study. |
|
Recruiting Locations
UAB Nephrology Research Clinic
Birmingham, Alabama 35233
Birmingham, Alabama 35233
More Details
- Status
- Recruiting
- Sponsor
- Hoffmann-La Roche
Study Contact
WA43966 https://forpatients.roche.com/888-662-6728 (U.S. Only)
global-roche-genentech-trials@gene.com