Recruiting NCT05797610

A Study to Evaluate the Efficacy and Safety of Sefaxersen (RO7434656) in Participants With Primary Immunoglobulin A (IgA) Nephropathy at High Risk of Progression

Phase III Interventional Primary IgA Nephropathy

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Sefaxersen (RO7434656), Placebo.
Who it may be relevant to: Registry conditions: Primary IgA Nephropathy. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Brazil, Canada +16
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sefaxersen, an Antisense Inhibitor of Complement Factor B, in Patients With Primary IgA Nephropathy at High Risk of Progression

Overview

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

Drug Sefaxersen (RO7434656)
Sefaxersen (RO7434656) will be administered as SC injection per schedule as specified.
Drug Placebo
Matching placebo will be administered as SC injection per schedule as specified.

Primary outcome measures

Change From Baseline in the Urine Protein-to-Creatinine Ratio (UPCR) at Week 37 [Time frame: Baseline, Week 37]

Secondary outcome measures (6)

Estimated Glomerular Filtration Rate (eGFR) Slope at Week 105 from Baseline [Time frame: Baseline, Week 105]
Percentage of Participants Achieving Hematuria Resolution at Week 37 [Time frame: At Week 37]
Time to the Composite Kidney Failure Endpoint [Time frame: Up to approximately 36 months]
Change From Baseline in Fatigue at Week 105 [Time frame: Baseline, Week 105]
Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs) [Time frame: Up to approximately 36 months]
Plasma Concentration of Sefaxersen [Time frame: Up to approximately 36 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Quadruple blind
Primary purpose: Treatment