A Study to Evaluate the Efficacy and Safety of Sefaxersen (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 Sefaxersen, an Antisense Inhibitor of Complement Factor B, in Patients With Primary IgA Nephropathy at High Risk of Progression
2 other identifiers
interventional
459
21 countries
178
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Aug 2023
Longer than P75 for phase_3
178 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 22, 2023
CompletedFirst Posted
Study publicly available on registry
April 4, 2023
CompletedStudy Start
First participant enrolled
August 8, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
March 31, 2029
ExpectedAugust 14, 2026
August 1, 2026
3.1 years
March 22, 2023
August 13, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (6)
Estimated Glomerular Filtration Rate (eGFR) Slope at Week 105 from Baseline
Baseline, Week 105
Percentage of Participants Achieving Hematuria Resolution at Week 37
At Week 37
Time to the Composite Kidney Failure Endpoint
Up to approximately 36 months
Change From Baseline in Fatigue at Week 105
Baseline, Week 105
Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs)
Up to approximately 36 months
- +1 more secondary outcomes
Other Outcomes (1)
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
Baseline, Week 105
Study Arms (2)
Sefaxersen (RO7434656)
EXPERIMENTALParticipants will receive subcutaneous (SC) doses of sefaxersen (RO7434656) on Days 1, 15, and 29 followed by once every 4 weeks (Q4W) until Week 105. Participants may be eligible to switch to open-label treatment after Week 105 at the investigator's discretion or after the common-close timepoint, whichever occurs first. The common-close timepoint is defined as the data cut-off date for the primary analysis, when approximately 230 participants in the primary cohort have completed the Week 105 visit.
Placebo
PLACEBO COMPARATORParticipants will receive SC doses of sefaxersen (RO7434656) matching placebo on Days 1, 15, and 29 followed by once Q4W until Week 105. Participants may be eligible to switch to open-label treatment after Week 105 at the investigator's discretion or after the common-close timepoint, whichever occurs first. The common-close timepoint is defined as the data cut-off date for the primary analysis, when approximately 230 participants in the primary cohort have completed the Week 105 visit.
Interventions
Sefaxersen (RO7434656) will be administered as SC injection per schedule as specified.
Eligibility Criteria
You may qualify if:
- 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/1.73 m\^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
You may not qualify if:
- 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 millimetre of mercury (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
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (178)
UAB Nephrology Research Clinic
Birmingham, Alabama, 35233, United States
Kidney Disease Medical Group Inc-1505 Wilson Ter
Glendale, California, 91206-4032, United States
Academic Medical Research Institute - Los Angeles
Los Angeles, California, 90022, United States
University of California, Los Angeles (UCLA) - Hematology/Oncology Santa Monica
Los Angeles, California, 90025-4837, United States
North America Research Institute-San Dimas
San Dimas, California, 91773, United States
Central Florida Kidney Specialists
Orlando, Florida, 32806, United States
L&C Professional Medical Research Institute
West Miami, Florida, 33144, United States
Cowry Medical Group LLC
Acworth, Georgia, 30101, United States
Care Institute Idaho Kidney Institute
Idaho Falls, Idaho, 83402, United States
Nephrology Associates of Northern Illinois
Hinsdale, Illinois, 60521, United States
Massachussets General Hospital
Boston, Massachusetts, 02114, United States
Sierra Nevada Nephrology Consultants
Reno, Nevada, 89511, United States
North Carolina Nephrology, PA
Raleigh, North Carolina, 27609, United States
Texas Kidney Institute - Dallas
Dallas, Texas, 75231, United States
Pioneer Research Solutions
Houston, Texas, 077099, United States
Prolato Clinical Research Center
Houston, Texas, 77054, United States
R & H Clinical Research
Katy, Texas, 77449, United States
Revival Research Institute - McKinney
McKinney, Texas, 75071, United States
Nephrology Associates of Northern Virginia Inc
Fairfax, Virginia, 22033, United States
Virginia Commonwealth University
Richmond, Virginia, 23298, United States
Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada
Ciudad Autonoma Buenos Aires, C1425AGC, Argentina
Consultorios Médicos Dr. Doreski
Ciudad Autonoma Buenos Aires, C1426ABP, Argentina
Sanatorio Mayo Privado
Córdoba, 5000, Argentina
Sanatorio Allende
Córdoba, X5000JHQ, Argentina
Instituto Medico de la Fundacion Estudios Clinicos
Rosario, S2013DTC, Argentina
Nepean Hospital
Kingswood, New South Wales, 02747, Australia
St George Hospital
Kogarah, New South Wales, 2217, Australia
Liverpool Hospital
Liverpool, New South Wales, 2170, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102, Australia
Royal Adelaide Hospital
Adelaide, South Australia, SA5000, Australia
Royal Melbourne Hospital
Parkville, Victoria, 3050, Australia
Sunshine Hospital
St Albans, Victoria, 3021, Australia
Santa Casa de Misericordia de Belo Horizonte - PPDS
Belo Horizonte, Minas Gerais, 30150-221, Brazil
Freire Pesquisa Clinica
Belo Horizonte, Minas Gerais, 30150, Brazil
Hospital de Clinicas de Porto Alegre HCPA PPDS
Porto Alegre, Rio Grande do Sul, 90035-903, Brazil
Faculdade de Medicina da Universidade de Sao Paulo
São Paulo, São Paulo, 01246, Brazil
Hospital Do Rim E Hipertensao Fundacao Oswaldo Ramos
São Paulo, São Paulo, 04038-002, Brazil
Instituto D?Or Pesquisa e Ensino - Hospital Gloria D?Or
Rio de Janeiro, 22281, Brazil
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9, Canada
Cape Breton Regional Hospital
Sydney, Nova Scotia, B1P 1P3, Canada
London Health Sciences Centre · Victoria Hospital
London, Ontario, N6A 5W9, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5, Canada
Montreal General Hospital
Montreal, Quebec, H3G 1A4, Canada
Centre Hospitalier Universitaire de Quebec
Québec, G1R 2J6, Canada
Beijing Friendship Hospital, Capital Medical University - PPDS
Beijing, Beijing Municipality, 000000, China
Cangzhou Central Hospital
Cangzhou Shi, Hebei, 060001, China
The First Hospital of Hebei Medical University
Shijiazhuang, Hebei, 050031, China
Wuxi People's Hospital
Wuxi, Jiangsu, 214023, China
Peking University First Hospital
Beijing, 100034, China
Peking University People's Hospital
Beijing, 100044, China
Changzhou First People's Hospital
Changzhou, 213003, China
West China Hospital, Sichuan University
Chengdu, 610041, China
Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
Chengdu, 610072, China
Guangdong Provincial People's Hospital
Guangzhou, 510080, China
Zhejiang Provincial People?s Hospital
Hangzhou, 310014, China
Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
Hangzhou, 310016, China
The First Affiliated Hospital of Nanchang University
Nanchang, 330000, China
The Second Affiliated Hospital of Nanjing Medical University
Nanjing, 210003, China
Ningbo No.2 Hospital
Ningbo, 315000, China
Ruijin Hospital Shanghai Jiaotong University School of Medicine
Shanghai, 200025, China
Xinhua Hospital Affiliated To Shanghai Jiaotong University School of Medicine
Shanghai, China
Shenzhen People's Hospital
Shenzhen, 518020, China
The University of Hong Kong - Shenzhen Hospital
Shenzhen, 518053, China
The Second Affiliated Hospital of Soochow University
Suzhou, 215004, China
Renmin Hospital of Wuhan University
Wuhan, 430060, China
The First Affiliated Hospital of Xian Jiao Tong University
Xi'an, 710061, China
General Hospital of Ningxia Medical University
Yinchuan, 750004, China
Affiliated Hospital of Jiangsu University
Zhenjiang, 212001, China
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05, Czechia
Vseobecna fakultni nemocnice v Praze
Prague, 12808, Czechia
Centre Hospitalier
Annonay, 07103, France
CHU Boulogne sur Mer
Boulogne-sur-Mer, 62200, France
Hopital Henri Mondor
Créteil, 94000, France
Hopital Tenon
Paris, 75020, France
Hopital Bichat - Claude Bernard AP-HP
Paris, 75877, France
Hôpital de Rangueil
Toulouse, 31059, France
Universitätsklinikum Leipzig
Leipzig, Saxony, 04103, Germany
Universitatsklinikum der RWTH Aachen
Aachen, 52074, Germany
Charite Universitaetsmedizin Berlin - Campus Charite Mitte
Berlin, 10117, Germany
St. Joseph-Krankenhaus
Berlin, 12101, Germany
Klinikum Koln-Merheim
Cologne, 51109, Germany
Medizinische Hochschule Hannover
Hanover, 30625, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, 55101, Germany
Robert-Bosch-Krankenhaus
Stuttgart, 70376, Germany
Nephrologisches Zentrum Villingen-Schwenningen
Villingen-Schwenningen, 78052, Germany
University General Hospital of Heraklion
Heraklion, 71110, Greece
Venizeleio General Hospital of Heraklion
Heraklion, 714 09, Greece
University General Hospital of Patras
Pátrai, 265 04, Greece
Queen Mary Hospital
Hong Kong, 999077, Hong Kong
Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari
Bari, Apulia, 70124, Italy
Azienda Ospedaliera Universitaria Federico II
Naples, Campania, 80131, Italy
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi-Via Massarenti
Bologna, Emilia-Romagna, 40138, Italy
Fondazione Policlinico Universitario A Gemelli
Rome, Lazio, 00168, Italy
Ospedale Policlinico San Martino
Genoa, Liguria, 16132, Italy
IRCCS Pavia - Istituti Clinici Scientifici Maugeri Spa ? Società Benefit
Pavia, Lombardy, 27100, Italy
Ospedale San Giovanni Bosco
Turin, Piedmont, 10154, Italy
Fujita Health University Hospital
Aichi, 470-1192, Japan
Hirosaki University Hospital
Aomori, 036-8563, Japan
Juntendo University Urayasu Hospital
Chiba, 279-0021, Japan
University of Yamanashi Hospital
Chūō, 409-3821, Japan
Matsuyama Red Cross Hospital
Ehime, 790-8524, Japan
Japanese Red Cross Fukuoka Hospital
Fukuoka, 815-8555, Japan
Hiroshima University Hospital
Hiroshima, 734-8551, Japan
Hokkaido University Hospital
Hokkaido, 060-8648, Japan
Hyogo Prefectural Nishinomiya General Medical Center
Hyōgo, 663-8241, Japan
Tokyo Medical University Ibaraki Medical Center
Inashiki-Gun, 300-0395, Japan
Kanazawa Medical University Hospital
Ishikawa, 920-0293, Japan
Nara Medical University Hospital
Kashihara, 634-8522, Japan
Kumamoto University Hospital
Kumamoto, 860-8556, Japan
Tohoku University Hospital
Miyagi, 980-8574, Japan
Kyoto City Hospital
Nakagyo-ku, 604-8845, Japan
Nara Prefecture General Medical Center
Nara, 630-8054, Japan
Iwate Medical University Hospital
Numakunai, 028-3695, Japan
National Hospital Organization Okayama Medical Center
Okayama, 701-1192, Japan
Okayama University Hospital
Okayama-Shi Kita-Ku, 700-0914, Japan
University of the Ryukyus Hospital
Okinawa, 903-0125, Japan
Saitama Medical University Hospital
Saitama, 350-0451, Japan
Osaka University Hospital
Suita, 565-0871, Japan
Jichi Medical University Hospital
Tochigi, 329-0498, Japan
Tokushima University Hospital
Tokushima, 770-8503, Japan
The Jikei University Hospital
Tokyo, 105-8471, Japan
Juntendo University Hospital
Tokyo, 113-8431, Japan
Tokyo Women's Medical University Hospital
Tokyo, 162-8666, Japan
Juntendo University Nerima Hospital, department of renal and hypertension
Tokyo, 177-8521, Japan
University of Tsukuba Hospital
Tsukuba, 305-8576, Japan
Yamaguchi University Hospital
Ube, 755-8505, Japan
Hospital Kuala Lumpur
Kuala Lumpur, FED. Territory of Kuala Lumpur, 50586, Malaysia
University Malaya Medical Centre
Kuala Lumpur, FED. Territory of Kuala Lumpur, 59100, Malaysia
Hospital Tengku Ampuan Afzan
Kuantan, Pahang, 25100, Malaysia
Hospital Seri Manjung
Seri Manjong, Pahang, 32040, Malaysia
Taiping Hospital
Taiping, Perak, 34000, Malaysia
Hospital Sibu
Sibu, Sarawak, 96000, Malaysia
Hospital Ampang
Ampang, 68000, Malaysia
Miri Hospital
Miri, 98000, Malaysia
Clinica San Cosme
Fracc Lomas Del Campestre, Aguascalientes, 20129, Mexico
Centro de Investigacion Clinica Chapultepec S. A. de C. V.
Morelia, Michoacán, 58260, Mexico
Instituto Mexicano de Trasplantes
Cuernavaca, Morelos, 62448, Mexico
4. Wojskowy Szpital Kliniczny z Poliklinika SP ZOZ
Wroclaw, Lower Silesian Voivodeship, 53-114, Poland
SCM Clinic - Prywatny Szpital Specjalistyczny
Krakow, 31-559, Poland
SPZOZ Centralny Szpital Klin
Lodz, 92-213, Poland
Uniwersytecki Szpital Kliniczny w Opolu
Opole, 45401, Poland
Uniwersytecki Szpital Kliniczny w Poznaniu - Przybyszewskiego 49
Poznan, 60-355, Poland
Szpital Kliniczny Dzieciatka Jezus
Warsaw, 02-006, Poland
National University Hospital
Singapore, 119074, Singapore
Singapore General Hospital
Singapore, 169608, Singapore
Tan Tock Seng Hospital
Singapore, 308433, Singapore
Changi General Hospital
Singapore, 529889, Singapore
Hallym University Sacred Heart Hospital
Anyang-si, 14068, South Korea
Soon Chun Hyang University Hospital Bucheon
Bucheon-si, 420-767, South Korea
Chungbuk National University Hospital
Cheongju-si, 28644, South Korea
Ajou University Hospital
Gyeonggi-do, 443-380, South Korea
CHA Bundang Medical Center, CHA University
Seongnam-si, 13496, South Korea
Seoul National University Bundang Hospital
Seongnam-si, 13620, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Konkuk University Medical Center
Seoul, 05030, South Korea
Gangdong Kyung Hee University Hospital
Seoul, 05278, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
SMG-SNU Boramae Medical Center
Seoul, 156-707, South Korea
Hospital Universitari Arnau de Vilanova
Lleida, Lerida, 25198, Spain
Hospital Universitario Vall d'Hebron - PPDS
Barcelona, 08035, Spain
C.H. Regional Reina Sofia - PPDS
Córdoba, 14004, Spain
Hospital Ribera Polusa
Lugo, 27004, Spain
Hospital Universitario 12 De Octubre
Madrid, 28041, Spain
Hospital Universitario La Paz - PPDS
Madrid, 28046, Spain
Hospital Universitario Virgen del Rocio - PPDS
Seville, 41013, Spain
Changhua Christian Hospital
Changhua, 500, Taiwan
Chang Gung Medical Foundation
Kaohsiung City, 83301, Taiwan
China Medical University Hospital
Taichung, 40447, Taiwan
Far Eastern Memorial Hospital
Taipei, 220, Taiwan
Chang Gung Memorial Hospital, Linkou
Taoyuan City, 333, Taiwan
Taichung Veterans General Hospital
Xitun Dist., 40705, Taiwan
Mackay Memorial Hospital-Taipei branch
Zhongshan Dist., 10449, Taiwan
Addenbrookes Hospital
Cambridge, CB2 0QQ, United Kingdom
Leicester General Hospital
Leicester, LE5 4PW, United Kingdom
Guys and St Thomas Hospital
London, SE1 9RT, United Kingdom
Kings College Hospital
London, SE5 9RS, United Kingdom
Churchill Hospital
Oxford, OX3 7LE, United Kingdom
Salford Royal Hospital
Salford, M6 8HD, United Kingdom
Related Publications (2)
Tekendo-Ngongang C, Gleeson JG, Mignon L. Treating the Untreatable: Antisense Oligonucleotides as an Individualized Therapy for Rare Genetic Kidney Diseases. J Am Soc Nephrol. 2024 Dec 1;35(12):1774-1777. doi: 10.1681/ASN.0000000532. Epub 2024 Sep 27. No abstract available.
PMID: 39331470DERIVEDTunnicliffe DJ, Reid S, Craig JC, Samuels JA, Molony DA, Strippoli GF. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst Rev. 2024 Feb 1;2(2):CD003962. doi: 10.1002/14651858.CD003962.pub3.
PMID: 38299639DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 22, 2023
First Posted
April 4, 2023
Study Start
August 8, 2023
Primary Completion
August 31, 2026
Study Completion (Estimated)
March 31, 2029
Last Updated
August 14, 2026
Record last verified: 2026-08
Data Sharing
- IPD Sharing
- Will share
For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing