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

• ClinicalTrials.gov Identifier: NCT05797610
• Recruitment Status: Recruiting
• First Posted: April 4, 2023
• Last Update Posted: November 3, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Primary IgA Nephropathy	Drug: RO7434656; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 428 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of RO7434656, an Antisense Inhibitor of Complement Factor B, in Patients With Primary IgA Nephropathy at High Risk of Progression
• Actual Study Start Date: August 8, 2023
• Estimated Primary Completion Date: September 30, 2026
• Estimated Study Completion Date: September 30, 2030

Arms and Interventions

Arm	Intervention/treatment
Experimental: RO7434656; Participants will receive subcutaneous (SC) doses of RO7434656 on Days 1, 15, and 29 followed by once every 4 weeks until Week 105. After Week 105, participants may continue blinded treatment or enter open-label treatment up to 1 year after the date at which the last participant completes the Week 105 assessment, withdraws, or is discontinued from the study.	Drug: RO7434656; RO7434656 will be administered subcutaneously per schedule as specified.
Placebo Comparator: Placebo; Participants will receive SC doses of RO7434656 matching placebo on Days 1, 15, and 29 followed by once every 4 weeks until Week 105. After Week 105, participants may continue blinded treatment or enter open-label treatment up to 1 year after the date at which 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.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in the Urine Protein-to-Creatinine Ratio (UPCR) at Week 37 [ Time Frame: Baseline, Week 37 ]
   UPCR will be assessed in urine sampled over 24 hours.

Secondary Outcome Measures :

1. Estimated Glomerular Filtration Rate (eGFR) Slope at Week 105 from Baseline [ Time Frame: Baseline, Week 105 ]
   eGFR will be calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation.
2. Time to the Composite Kidney Failure Endpoint [ Time Frame: Up to approximately 7 years ]
   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% (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.
3. Change From Baseline in Fatigue at Week 105 [ Time Frame: Baseline, 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.
4. Change From Baseline in Symptoms and Health-Related Quality of Life at Week 105 as Assessed Using the Kidney Disease and Quality of Life 36-Item (KDQOL-36) Short Form [ Time Frame: Baseline, Week 105 ]
   The KDQOL-36 is an abbreviated questionnaire that combines generic and disease-specific components to assess participant's health-related quality of life. This 36-item questionnaire includes the Short Form 12 (SF-12), Version 1 (12 items) and 3 disease-related domains, symptoms/problems (12 items), burden of kidney disease (4 items), and effects of kidney disease (8 items). It uses a recall of 4 weeks, and items are assessed on 3- to 5-point Likert scales or with a dichotomous response option. Higher score indicates better health. The raw scores are transformed linearly to a range of 0 to 100, with higher scores indicating better health.
5. Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to approximately 7 years ]
6. Plasma Concentration of RO7434656 [ Time Frame: Up to approximately 7 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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
• 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

Contacts and Locations

Contacts

Contact: WA43966 https://forpatients.roche.com/; 888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

Locations

United States, Arizona

Tucson Neuroscience Research - M3 WR; Recruiting

Tucson, Arizona, United States, 85710

United States, California

Southern California Medical Research Center; Recruiting

La Palma, California, United States, 90623

North America Research Institute-San Dimas; Recruiting

San Dimas, California, United States, 91773

United States, Florida

LCC Medical Research - Miami - ClinEdge - PPDS; Recruiting

Miami, Florida, United States, 33126

United States, Georgia

Cowry Medical Group LLC; Recruiting

Acworth, Georgia, United States, 30101

United States, Nevada

Sierra Nevada Nephrology Consultants; Recruiting

Reno, Nevada, United States, 89511

United States, North Carolina

North Carolina Nephrology, PA; Recruiting

Raleigh, North Carolina, United States, 27609

United States, Texas

Global Medical Research - M3 WR; Completed

Dallas, Texas, United States, 75224

Texas Kidney Institute - Dallas; Recruiting

Dallas, Texas, United States, 75231

Pioneer Research Solutions; Recruiting

Houston, Texas, United States, 077099

Prolato Clinical Research Center; Recruiting

Houston, Texas, United States, 77054

R & H Clinical Research; Recruiting

Katy, Texas, United States, 77494-2031

United States, Virginia

Nephrology Associates of Northern Virginia Inc; Recruiting

Fairfax, Virginia, United States, 22033

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT05797610
• Other Study ID Numbers: WA43966; 2022-502102-32-00 ( Other Identifier: EU Clinical Trial Number )
• First Posted: April 4, 2023
• Last Update Posted: November 3, 2023
• Last Verified: November 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Kidney Diseases; Glomerulonephritis, IGA; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Glomerulonephritis; Nephritis; Autoimmune Diseases; Immune System Diseases