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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Primary IgA Nephropathy
• Intervention / Treatment: Drug: RO7434656; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 428
• Phase: Phase 3

Contacts and Locations

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

Study Locations

• Argentina
  • Ciudad Autonoma Buenos Aires, Argentina, C1426ABP
    • Recruiting
    • Consultorios Médicos Dr. Doreski
  • Ciudad Autónoma de Buenos Aires, Argentina, C1425
    • Recruiting
    • Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada
  • Cordoba, Argentina, X5000JHQ
    • Recruiting
    • Sanatorio Allende
  • Rosario, Argentina, S2000DEJ
    • Recruiting
    • Instituto Medico de La Fundacion Estudios Clinicos
• Australia
  • New South Wales
    • Kingswood, New South Wales, Australia, 02747
      • Recruiting
      • Nepean Hospital
    • Kogarah, New South Wales, Australia, 2217
      • Recruiting
      • St George Hospital
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Recruiting
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Royal Adelaide Hospital
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Recruiting
      • Royal Melbourne Hospital
    • St Albans, Victoria, Australia, 3021
      • Recruiting
      • Sunshine Hospital
• Brazil
  • MG
    • Belo Horizonte, MG, Brazil, 30150-221
      • Recruiting
      • Santa Casa de Misericordia de Belo Horizonte - PPDS
    • Belo Horizonte, MG, Brazil, 30150
      • Recruiting
      • Freire Pesquisa Clinica
  • PA
    • Porto Alegre, PA, Brazil, 90035-903
      • Recruiting
      • Hospital de Clinicas de Porto Alegre HCPA PPDS
  • SC
    • Joinville, SC, Brazil, 89227-680
      • Recruiting
      • Centro de Pesquisa Clinica da Fundação Pró Rim
  • SP
    • Sao Paulo, SP, Brazil, 01246
      • Recruiting
      • Faculdade de Medicina da Universidade de Sao Paulo
• China
  • Beijing City, China, 100034
    • Recruiting
    • Peking University First Hospital
  • Beijing City, China, 100050
    • Recruiting
    • Beijing Friendship Hospital, Capital Medical University - PPDS
  • Changzhou, China, 213003
    • Recruiting
    • Changzhou First People's Hospital
  • Chengdu City, China, 610072
    • Recruiting
    • Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
  • Guangzhou City, China, 510115
    • Recruiting
    • Guangdong Provincial People?s Hospital
  • Hangzhou, China, 310014
    • Recruiting
    • Zhejiang Provincial People?s Hospital
  • Hangzhou City, China, 310016
    • Recruiting
    • Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
  • Nanjing, China, 210003
    • Recruiting
    • The Second Affiliated Hospital of Nanjing Medical University
  • Ningbo, China
    • Recruiting
    • Ningbo No.2 Hospital
  • Shenzhen City, China, 518020
    • Recruiting
    • ShenZhen People's Hospital
  • Suzhou, China, 215004
    • Recruiting
    • The Second Affiliated Hospital of Soochow University
  • Xi'an City, China, 710061
    • Recruiting
    • The First Affiliated Hospital of Xian Jiao Tong University
  • Yinchuan, China, 750004
    • Recruiting
    • General Hospital of Ningxia Medical University
  • Zhenjiang, China, 212001
    • Recruiting
    • Affiliated Hospital of Jiangsu University
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Recruiting
    • Fakultni nemocnice Hradec Kralove
• France
  • Annonay, France, 07103
    • Recruiting
    • Centre Hospitalier; Hemodialyse
  • Boulogne Sur Mer, France, 62200
    • Recruiting
    • CHU Boulogne sur Mer
  • Creteil, France, 94010
    • Recruiting
    • Hopital Henri Mondor
  • Paris, France, 75877
    • Recruiting
    • Hopital Bichat - Claude Bernard AP-HP
  • Paris, France, 75020
    • Recruiting
    • Hopital Tenon; AP HP
  • Toulouse, France, 31059
    • Recruiting
    • Hopital de Rangueil
• Germany
  • Aachen, Germany, 52074
    • Recruiting
    • Universitatsklinikum der RWTH Aachen
  • Mainz, Germany, 55101
    • Recruiting
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
• Greece
  • Heraklio, Greece, 711 10
    • Recruiting
    • University General Hospital of Heraklion
  • Irakleio Kritis, Greece, 714 09
    • Recruiting
    • Venizeleio General Hospital of Heraklion
  • Patras, Greece, 265 00
    • Recruiting
    • University General Hospital of Patras
  • Thessaloniki, Greece, 546 42
    • Recruiting
    • Ippokratio General Hospital of Thessaloniki
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Recruiting
      • Azienda Ospedaliera Universitaria Federico II
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Recruiting
      • Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi-Via Massarenti
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario A Gemelli
  • Liguria
    • Genova, Liguria, Italy, 16132
      • Recruiting
      • Ospedale Policlinico San Martino
  • Lombardia
    • Pavia, Lombardia, Italy, 27100
      • Recruiting
      • IRCCS Pavia - Istituti Clinici Scientifici Maugeri Spa ? Società Benefit
• Japan
  • Nara, Japan, 630-8054
    • Recruiting
    • Nara Prefecture General Medical Center
  • Nishinomiya, Japan, 662-0918
    • Recruiting
    • Hyogo Prefectural Nishinomiya Hospital
  • Okayama, Japan, 701-1192
    • Recruiting
    • National Hospital Organization Okayama Medical Center
  • Suita, Japan, 565-0871
    • Recruiting
    • Osaka University Hospital
• Korea, Republic of
  • Bucheon-si,, Korea, Republic of, 420-767
    • Recruiting
    • Soon Chun Hyang University Hospital Bucheon
  • Cheongju si, Korea, Republic of, 28644
    • Recruiting
    • Chungbuk National University Hospital
  • Gyeonggi-Do, Korea, Republic of, 431-070
    • Recruiting
    • Hallym University Sacred Heart Hospital
  • Gyeonggi-do, Korea, Republic of, 13620
    • Recruiting
    • Seoul National University Bundang Hospital; Neurology Department
  • Seongnam-si, Korea, Republic of, 13496
    • Recruiting
    • CHA Bundang Medical Center, CHA University
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05030
    • Recruiting
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center; Nephrology Department
  • Seoul, Korea, Republic of, 05278
    • Recruiting
    • Gangdong Kyung Hee University Hospital
• Poland
  • Kraków, Poland, 31-559
    • Recruiting
    • SCM Clinic - Prywatny Szpital Specjalistyczny
  • Lodz, Poland, 92-213
    • Recruiting
    • SPZOZ Centralny Szpital Klin; UM w Lodzi
  • Pozna?, Poland, 60-355
    • Recruiting
    • Szpital Kliniczny im. H.Swiecickiego UM w Poznaniu
  • Warszawa, Poland, 02-005
    • Recruiting
    • Szpital Kliniczny Dzieciatka Jezus
• Singapore
  • Singapore, Singapore, 169608
    • Recruiting
    • Singapore General Hospital
  • Singapore, Singapore, 119074
    • Recruiting
    • National University Hospital
  • Singapore, Singapore, 529889
    • Recruiting
    • Changi General Hospital
  • Singapore, Singapore, 308433
    • Recruiting
    • Tan Tock Seng Hospital; Department of Renal Medicine
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitario Vall d'Hebron - PPDS
  • Lugo, Spain, 27004
    • Recruiting
    • Hospital Ribera Polusa
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz - PPDS
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocio - PPDS
• Taiwan
  • Chang Hua, Taiwan, 500
    • Recruiting
    • Changhua Christian Hospital
  • Taichung, Taiwan, 40447
    • Recruiting
    • China Medical University Hospital
  • Taipei, Taiwan, 220
    • Recruiting
    • Far Eastern Memorial Hospital; Department of Clinical Pathology
  • Taipei, Taiwan, 10449
    • Recruiting
    • Mackay Memorial Hospital-Taipei branch; Clinical Trial Pharmacy
  • Taoyuan City, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hospital, Linkou; Department of Pediatric Internal Medicine
• United Kingdom
  • Oxford, United Kingdom, OX3 7LJ
    • Recruiting
    • Churchill Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85710
      • Recruiting
      • Tucson Neuroscience Research - M3 WR
  • California
    • La Palma, California, United States, 90623
      • Recruiting
      • Southern California Medical Research Center
    • San Dimas, California, United States, 91773
      • Recruiting
      • North America Research Institute-San Dimas
  • Florida
    • Hialeah, Florida, United States, 33010
      • Recruiting
      • Hope Clinic & Research Center
    • Miami, Florida, United States, 33126
      • Recruiting
      • LCC Medical Research - Miami - ClinEdge - PPDS
  • Georgia
    • Acworth, Georgia, United States, 30101
      • Recruiting
      • Cowry Medical Group LLC
  • Illinois
    • Hinsdale, Illinois, United States, 60521
      • Recruiting
      • Nephrology Associates of Northern Illinois
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachussets General Hospital
  • Nevada
    • Reno, Nevada, United States, 89511
      • Recruiting
      • Sierra Nevada Nephrology Consultants
  • New York
    • Mineola, New York, United States, 11501
      • Recruiting
      • NYU Langone Nephrology Associates - Mineola
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
      • Recruiting
      • North Carolina Nephrology, PA
  • Texas
    • Dallas, Texas, United States, 75231
      • Recruiting
      • Texas Kidney Institute - Dallas
    • Dallas, Texas, United States, 75224
      • Withdrawn
      • Global Medical Research - M3 WR
    • Houston, Texas, United States, 77054
      • Recruiting
      • Prolato Clinical Research Center
    • Houston, Texas, United States, 077099
      • Recruiting
      • Pioneer Research Solutions
    • Katy, Texas, United States, 77494-2031
      • Recruiting
      • R & H Clinical Research
    • Sherman, Texas, United States, 75092
      • Recruiting
      • Revival Research Corporation - Sherman - ClinEdge - PPDS
  • Virginia
    • Fairfax, Virginia, United States, 22033
      • Recruiting
      • Nephrology Associates of Northern Virginia Inc
    • Richmond, Virginia, United States, 23219-1901
      • Recruiting
      • Virginia Commonwealth University
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Milwaukee Nephrologists, SC

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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 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.	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 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.	Drug: Placebo; Matching placebo will be administered subcutaneously per schedule as specified.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Week 105
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.	Baseline, Week 105
Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs)		Up to approximately 7 years
Plasma Concentration of RO7434656		Up to approximately 7 years
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 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.	Up to approximately 7 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Baseline, Week 105

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2030

Study Registration Dates

• First Submitted: March 22, 2023
• First Submitted That Met QC Criteria: March 22, 2023
• First Posted (Actual): April 4, 2023

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Glomerulonephritis, IGA
• Other Study ID Numbers: WA43966; 2022-502102-32-00 (Other Identifier: EU Clinical Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No