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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 Sex: 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.	Drug: sefaxersen (RO7434656) Sefaxersen (RO7434656) will be administered subcutaneously per schedule as specified. Other names: sefaxersen
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.	Drug: Placebo Matching placebo will be administered subcutaneously per schedule as specified.

Recruiting Locations

UAB Nephrology Research Clinic
Birmingham, Alabama 35233

Sunrise Medical Management LLC
Surprise, Arizona 85374-8644

Academic Medical Research Institute - Los Angeles
Los Angeles, California 90022

UCLA University of California Los Angeles
Los Angeles, California 90095

North America Research Institute-San Dimas
San Dimas, California 91773

LCC Medical Research - Miami - ClinEdge - PPDS
Miami, Florida 33126

L&C Professional Medical Research Institute
W. Miami, Florida 33144

Cowry Medical Group LLC
Acworth, Georgia 30101

Care Institute Idaho Kidney Institute
Chubbuck, Idaho 83202

Nephrology Associates of Northern Illinois
Hinsdale, Illinois 60521

University of Iowa
Iowa City, Iowa 52242

Massachussets General Hospital
Boston, Massachusetts 02114

University of Mississippi Medical Center
Jackson, Mississippi 39216

Sierra Nevada Nephrology Consultants
Reno, Nevada 89511

NYU Langone Nephrology Associates - Mineola
Mineola, New York 11501

North Carolina Nephrology, PA
Raleigh, North Carolina 27609

Ohio State University Wexner Medical Center - Outpatient Care East
Columbus, Ohio 43203

Texas Kidney Institute - Dallas
Dallas, Texas 75231

Pioneer Research Solutions
Houston, Texas 077099

Prolato Clinical Research Center
Houston, Texas 77054

R & H Clinical Research
Katy, Texas 77450

Revival Research Corporation - Sherman - ClinEdge - PPDS
Sherman, Texas 75092

Nephrology Associates of Northern Virginia Inc
Fairfax, Virginia 22033

Virginia Commonwealth University
Richmond, Virginia 23298

Milwaukee Nephrologists, Sc
Wauwatosa, Wisconsin 53226

More Details

NCT ID: NCT05797610
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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.