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Phase III: Sefaxersen in Primary IgA Nephropathy (IMAgINATION)

Clinical Trial Overview

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

Objective

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.

ASO=Antisense Oligonucleotide; IgAN=IgA nephropathy

Primary Endpoints

Change From Baseline in the Urine Protein-to-Creatinine Ratio (UPCR) at Week 37

Secondary Endpoints

Estimated Glomerular Filtration Rate (eGFR) Slope at Week 105 from Baseline, eGFR will be calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation.
Time to the Composite Kidney Failure Endpoint, 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/minute/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, without the receipt of other immunosuppressive or background therapies for the treatment of IgAN.
Change From Baseline in Fatigue at 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)
Plasma Concentration of Sefaxersen

UPCR=Urine Protein-to-Creatinine Ratio; eGFR=Estimated Glomerular Filtration Rate; CKD-EPI=Chronic Kidney Disease Epidemiology Collaboration; mL/min/1.73m^2=milliliters/minute/1.73m^2; FACIT-F=Functional Assessment of Chronic Illness Therapy-Fatigue subscale; TEAEs=Treatment-Emergent Adverse Events; IgAN=IgA nephropathy

RO7434656

Modality: Novel Antisense Oligonucleotide (ASO) therapy

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Clinical Trial Overview

Inclusion and Exclusion Criteria

Enrollment and Resources

View on ClinicalTrials.gov

Inclusion and Exclusion Criteria

Key Inclusion Criteria

Key Exclusion 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/1.73m^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

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

ACE=angiotensin-converting enzyme; ARBs=angiotensin II receptor blockers; CKD-EPI=Chronic Kidney Disease Epidemiology Collaboration; eGFR=Estimated Glomerular Filtration Rate; g/day=gram per day; g/g=gram per gram; GIP=Glucose-dependent Insulinotropic Polypeptide; GLP-1=Glucagon-like Peptide-1; HbA1c=Hemoglobin A1c), also called glycated hemoglobin; IgAN=IgA nephropathy; IV=intravenous; mg/day=milligrams per day; mL/min/1.73m^2=milliliters/minute/1.73m^2; SGLT2=sodium-glucose cotransporter-2; UPCR=Urine Protein-to-Creatinine Ratio

Enrollment & Resources

Enrollment

For more information on eligibility criteria, view the study or reach out to our team.

Web

ClinicalTrials.gov
Identifier: NCT05797610

Phone

1-888-662-6728
(US and Canada)

Email

[email protected]

Clinical Trial Site Locations

Clinical Trial Site Locations

For more information on recruitment status, or where the study is being conducted

Visit ClinicalTrials.gov

Information is consistent with ClinicalTrials.gov as of January 16, 2026. Products under investigation have not been approved for use outside of the clinical trial setting. This information is presented only for the purposes of providing an overview of clinical trials and should not be construed as a recommendation for use of any product for unapproved purposes.

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ACE
angiotensin-converting enzyme
ARBs
angiotensin II receptor blockers
ASO
Antisense Oligonucleotide
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
eGFR
Estimated Glomerular Filtration Rate
FACIT-F
Functional Assessment of Chronic Illness Therapy-Fatigue subscale
g/day
gram per day
g/g
gram per gram
GIP
Glucose-dependent Insulinotropic Polypeptide
GLP-1
Glucagon-like Peptide-1
HbA1c
Hemoglobin A1c), also called glycated hemoglobin
IgAN
IgA nephropathy
IV
intravenous
mg/day
milligrams per day
mL/min/1.73m^2
milliliters/minute/1.73m^2
PK
pharmacokinetics
RO7434656
Sefaxersen (Molecule code)
SGLT2
sodium-glucose cotransporter-2
TEAEs
Treatment-Emergent Adverse Events
UPCR
Urine Protein-to-Creatinine Ratio