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

Primary IgA Nephropathy Clinical Trial

— IMAGINATION  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05797610
• Other study ID #: WA43966
• Secondary ID: 2022-502102-32-0
• Status: Recruiting
• Phase: Phase 3
• Start date: August 8, 2023
• Est. completion date: September 30, 2030

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: WA43966 https://forpatients.roche.com/
• Phone: 888-662-6728 (U.S. Only)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 428
• Est. completion date: September 30, 2030
• Est. primary completion date: September 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• Kidney Diseases
• Primary IgA Nephropathy

Intervention

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

Locations

Country	Name	City	State
Argentina	Consultorios Médicos Dr. Doreski	Ciudad Autonoma Buenos Aires
Argentina	Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada	Ciudad Autónoma de Buenos Aires
Argentina	Sanatorio Allende	Cordoba
Argentina	Instituto Medico de la Fundacion Estudios Clinicos	Rosario
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	St George Hospital	Kogarah	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Sunshine Hospital	St Albans	Victoria
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Brazil	Freire Pesquisa Clinica	Belo Horizonte	MG
Brazil	Santa Casa de Misericordia de Belo Horizonte - PPDS	Belo Horizonte	MG
Brazil	Centro de Pesquisa Clinica da Fundação Pró Rim	Joinville	SC
Brazil	Hospital de Clinicas de Porto Alegre HCPA PPDS	Porto Alegre	PA
Brazil	Faculdade de Medicina da Universidade de Sao Paulo	Sao Paulo	SP
China	Beijing Friendship Hospital, Capital Medical University - PPDS	Beijing City
China	Peking University First Hospital	Beijing City
China	Changzhou First People's Hospital	Changzhou
China	Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital	Chengdu City
China	Guangdong Provincial People?s Hospital	Guangzhou City
China	Zhejiang Provincial People?s Hospital	Hangzhou
China	Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University	Hangzhou City
China	The Second Affiliated Hospital of Nanjing Medical University	Nanjing
China	Ningbo No.2 Hospital	Ningbo
China	Shenzhen People's Hospital	Shenzhen City
China	The Second Affiliated Hospital of Soochow University	Suzhou
China	The First Affiliated Hospital of Xian Jiao Tong University	Xi'an City
China	General Hospital of Ningxia Medical University	Yinchuan
China	Affiliated Hospital of Jiangsu University	Zhenjiang
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
France	Centre Hospitalier; Hemodialyse	Annonay
France	CHU Boulogne sur Mer	Boulogne Sur Mer
France	Hopital Henri Mondor	Creteil
France	Hopital Bichat - Claude Bernard AP-HP	Paris
France	Hopital Tenon; AP HP	Paris
France	Hôpital de Rangueil	Toulouse
Germany	Universitatsklinikum der RWTH Aachen	Aachen
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Greece	University General Hospital of Heraklion	Heraklio
Greece	Venizeleio General Hospital of Heraklion	Irakleio Kritis
Greece	University General Hospital of Patras	Patras
Greece	Ippokratio General Hospital of Thessaloniki	Thessaloniki
Italy	Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi-Via Massarenti	Bologna	Emilia-Romagna
Italy	Ospedale Policlinico San Martino	Genova	Liguria
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli	Campania
Italy	IRCCS Pavia - Istituti Clinici Scientifici Maugeri Spa ? Società Benefit	Pavia	Lombardia
Italy	Fondazione Policlinico Universitario A Gemelli	Roma	Lazio
Japan	Nara Prefecture General Medical Center	Nara
Japan	Hyogo Prefectural Nishinomiya Hospital	Nishinomiya
Japan	National Hospital Organization Okayama Medical Center	Okayama
Japan	Osaka University Hospital	Suita
Korea, Republic of	Soon Chun Hyang University Hospital Bucheon	Bucheon-si,
Korea, Republic of	Chungbuk National University Hospital	Cheongju si
Korea, Republic of	Hallym University Sacred Heart Hospital	Gyeonggi-Do
Korea, Republic of	Seoul National University Bundang Hospital; Neurology Department	Gyeonggi-do
Korea, Republic of	CHA Bundang Medical Center, CHA University	Seongnam-si
Korea, Republic of	Gangdong Kyung Hee University Hospital	Seoul
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	Samsung Medical Center; Nephrology Department	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Poland	SCM Clinic - Prywatny Szpital Specjalistyczny	Kraków
Poland	SPZOZ Centralny Szpital Klin; UM w Lodzi	Lodz
Poland	Szpital Kliniczny im. H.Swiecickiego UM w Poznaniu	Pozna?
Poland	Szpital Kliniczny Dzieciatka Jezus	Warszawa
Singapore	Changi General Hospital	Singapore
Singapore	National University Hospital	Singapore
Singapore	Singapore General Hospital	Singapore
Singapore	Tan Tock Seng Hospital; Department of Renal Medicine	Singapore
Spain	Hospital Universitario Vall d'Hebron - PPDS	Barcelona
Spain	Hospital Ribera Polusa	Lugo
Spain	Hospital Universitario 12 De Octubre	Madrid
Spain	Hospital Universitario La Paz - PPDS	Madrid
Spain	Hospital Universitario Virgen del Rocio - PPDS	Sevilla
Taiwan	Changhua Christian Hospital	Chang Hua
Taiwan	China Medical University Hospital	Taichung
Taiwan	Far Eastern Memorial Hospital; Department of Clinical Pathology	Taipei
Taiwan	Mackay Memorial Hospital-Taipei branch; Clinical Trial Pharmacy	Taipei
Taiwan	Chang Gung Memorial Hospital, Linkou; Department of Pediatric Internal Medicine	Taoyuan City
United Kingdom	Churchill Hospital	Oxford
United States	Cowry Medical Group LLC	Acworth	Georgia
United States	Massachussets General Hospital	Boston	Massachusetts
United States	Global Medical Research - M3 WR	Dallas	Texas
United States	Texas Kidney Institute - Dallas	Dallas	Texas
United States	Nephrology Associates of Northern Virginia Inc	Fairfax	Virginia
United States	Hope Clinic & Research Center	Hialeah	Florida
United States	Nephrology Associates of Northern Illinois	Hinsdale	Illinois
United States	Pioneer Research Solutions	Houston	Texas
United States	Prolato Clinical Research Center	Houston	Texas
United States	R & H Clinical Research	Katy	Texas
United States	Southern California Medical Research Center	La Palma	California
United States	LCC Medical Research - Miami - ClinEdge - PPDS	Miami	Florida
United States	Milwaukee Nephrologists, Sc	Milwaukee	Wisconsin
United States	NYU Langone Nephrology Associates - Mineola	Mineola	New York
United States	North Carolina Nephrology, PA	Raleigh	North Carolina
United States	Sierra Nevada Nephrology Consultants	Reno	Nevada
United States	Virginia Commonwealth University	Richmond	Virginia
United States	North America Research Institute-San Dimas	San Dimas	California
United States	Revival Research Corporation - Sherman - ClinEdge - PPDS	Sherman	Texas
United States	Tucson Neuroscience Research - M3 WR	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  China,  Czechia,  France,  Germany,  Greece,  Italy,  Japan,  Korea, Republic of,  Poland,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs)		Up to approximately 7 years
Secondary	Plasma Concentration of RO7434656		Up to approximately 7 years