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, 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 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

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

ArmDescriptionAssigned 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 (Q4W) 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 as SC injection 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 Q4W 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 as SC injection per schedule as specified.

Recruiting Locations

Alabama Kidney Research - ERN - PPDS
Alabaster 4829762, Alabama 4829764 35007-8823

UAB Nephrology Research Clinic
Birmingham 4049979, Alabama 4829764 35233

Sunrise Medical Management LLC
Surprise 5316428, Arizona 5551752 85374-8644

Kidney Disease Medical Group Inc-1505 Wilson Ter
Glendale 5352423, California 5332921 91206-4032

Academic Medical Research Institute - Los Angeles
Los Angeles 5368361, California 5332921 90022

University of California, Los Angeles (UCLA) - Hematology/Oncology Santa Monica
Los Angeles 5368361, California 5332921 90025-4837

Los Angeles County Nephrology
Montebello 5374322, California 5332921 90640-2217

North America Research Institute-San Dimas
San Dimas 5391891, California 5332921 91773

LCC Medical Research - Miami - ClinEdge - PPDS
Miami 4164138, Florida 4155751 33126

Central Florida Kidney Specialists
Orlando 4167147, Florida 4155751 32806

L&C Professional Medical Research Institute
West Miami 4177874, Florida 4155751 33144

Cowry Medical Group LLC
Acworth 4179074, Georgia 4197000 30101

Care Institute Idaho Kidney Institute
Chubbuck 5588842, Idaho 5596512 83202

Care Institute Idaho Kidney Institute
Idaho Falls 5596475, Idaho 5596512 83402

Nephrology Associates of Northern Illinois
Hinsdale 4896012, Illinois 4896861 60521

University of Iowa
Iowa City 4862034, Iowa 4862182 52242

Massachussets General Hospital
Boston 4930956, Massachusetts 6254926 02114

University of Mississippi Medical Center
Jackson 4431410, Mississippi 4436296 39216

Sierra Nevada Nephrology Consultants
Reno 5511077, Nevada 5509151 89511

NYU Langone Nephrology Associates - Mineola
Mineola 5127134, New York 5128638 11501

North Carolina Nephrology, PA
Raleigh 4487042, North Carolina 4482348 27609

Ohio State University Wexner Medical Center - Outpatient Care East
Columbus 4509177, Ohio 5165418 43203

Austin Diagnostic Clinic - Frenova F1
Austin 4671654, Texas 4736286 78751-3014

Texas Kidney Institute - Dallas
Dallas 4684888, Texas 4736286 75231

Pioneer Research Solutions
Houston 4699066, Texas 4736286 077099

Prolato Clinical Research Center
Houston 4699066, Texas 4736286 77054

R & H Clinical Research
Katy 4702732, Texas 4736286 77450

Revival Research Corporation - Sherman - ClinEdge - PPDS
Sherman 4728328, Texas 4736286 75092

Utah Kidney Research Institute
Salt Lake City 5780993, Utah 5549030 84115

Nephrology Associates of Northern Virginia Inc
Fairfax 4758023, Virginia 6254928 22033

Virginia Commonwealth University
Richmond 4781708, Virginia 6254928 23298

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

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ResearchMatch is funded in part by the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program, led by the NIH’s National Center for Advancing Translational Sciences (NCATS), grants UL1TR000445 and 1U54RR032646-01, and grant U24TR001579 from NCATS and the National Library of Medicine. The content of this website is solely the responsibility of ResearchMatch and Vanderbilt University and does not necessarily represent the official views of the NIH, NCATS, or NLM.

Vanderbilt University Medical Center