Primary IgA Nephropathy
Conditions
Brief summary
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.
Interventions
DRUGSefaxersen (RO7434656)
Sefaxersen (RO7434656) will be administered as SC injection per schedule as specified.
DRUGPlacebo
Matching placebo will be administered as SC injection per schedule as specified.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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, and without an intent to modify the dose during the study, 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 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 millimetre of mercury (mmHg) or diastolic blood pressure \>90 mmHg from the average of two measurements performed at least 1 minute apart during screening * Initiation of sodium-glucose cotransporter-2 (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 Glucagon-like Peptide-1 (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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Percentage of Participants Achieving Hematuria Resolution at Week 37 | At Week 37 | — |
| Time to the Composite Kidney Failure Endpoint | Up to approximately 36 months | 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 milliliters/minutes/1.73m\^2 (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. |
| 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. |
| Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs) | Up to approximately 36 months | — |
| Plasma Concentration of Sefaxersen | Up to approximately 36 months | — |
Countries
Argentina, Australia, Brazil, Canada, China, Czechia, France, Germany, Greece, Hong Kong, Italy, Japan, Malaysia, Mexico, Poland, Singapore, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed