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: May 10, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: March 22, 2023
• First Posted Date: April 4, 2023
• Last Update Posted Date: May 10, 2024
• Actual Study Start Date: August 8, 2023
• Estimated Primary Completion Date: September 30, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 22, 2023)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 18, 2023)

• 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.
• 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% or a sustained eGFR <15 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 [ 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.
• Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to approximately 7 years ]
• Plasma Concentration of RO7434656 [ Time Frame: Up to approximately 7 years ]

Original Secondary Outcome Measures (submitted: March 22, 2023)

• 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.
• 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.
• 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.
• 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.
• Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to approximately 7 years ]
• Plasma Concentration of RO7434656 [ Time Frame: Up to approximately 7 years ]

Current Other Pre-specified Outcome Measures (submitted: December 18, 2023)

Change From Baseline in Symptoms and Health-Related Quality of Life at Week 105 as Assessed Using the RAND Kidney Disease and Quality of Life 36-Item (KDQOL-36) Short Form [ Time Frame: Baseline, Week 105 ]

The RAND KDQOL-36 is an abbreviated questionnaire that combines the generic and disease-specific components to assess participant's health-related quality of life. This 36-item questionnaire includes the RAND 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.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Efficacy and Safety of RO7434656 in Participants With Primary Immunoglobulin A (IgA) Nephropathy at High Risk of Progression
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Primary IgA Nephropathy

Intervention

• Drug: RO7434656
  RO7434656 will be administered subcutaneously per schedule as specified.
• Drug: Placebo
  Matching placebo will be administered subcutaneously per schedule as specified.

Study Arms

• 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 until up to 1 year after the date at which the last participant completes the Week 105 assessment, withdraws, or is discontinued from the study.
  Intervention: Drug: RO7434656
• 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 until up to 1 year after the date at which the last participant completes the Week 105 assessment, withdraws, or is discontinued from the study.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 22, 2023): 428
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 30, 2030
• Estimated Primary Completion Date: September 30, 2026 (Final data collection date for primary outcome measure)

Eligibility 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 obtained no longer than 60 days prior to Day 1
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Argentina, Australia, Brazil, Canada, China, Czechia, France, Germany, Greece, Italy, Japan, Korea, Republic of, Poland, Singapore, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT05797610
• Other Study ID Numbers: WA43966; 2022-502102-32-00 ( Other Identifier: EU Clinical Trial Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

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).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: May 2024