Overview
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.
Principal investigator
Eligibility 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
* 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
Participate in this trial
Are you interested in enrolling in this study? Learn more here.
I'm Interested In ParticipatingFor Referring Providers
Do you have a patient you think would be a good candidate for this trial? Learn more about enrolling your patient.