A Study to Evaluate the Efficacy and Safety of Sefaxersen (RO7434656) in Participants With Primary Immunoglobulin A (IgA) Nephropathy at High Risk of Progression
- Conditions
- Primary IgA Nephropathy
- Interventions
- Drug: sefaxersen (RO7434656)Drug: Placebo
- Registration Number
- NCT05797610
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 428
- 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, 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 Chronic Kidney Disease Epidemiology Collaboration (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
- 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 mmHg or diastolic blood pressure >90 mmHg from the average of two measurements performed at least 1 minute apart during screening
- Initiation of 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
- Treatment with a systemic calcineurin inhibitor within 2 months prior to screening or during screening
- Treatment with anti-CD20 therapy within 9 months of screening or during screening
- Treatment with other systemic immunosuppressive agents within 6 months of randomization including, but not limited to, complement inhibitors, alkylating agents (e.g., cyclophosphamide or chlorambucil), azathioprine, or mycophenolate
- Planned major procedure or major surgery during screening or the study
- Substance abuse within 12 months prior to 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
- History of malignancy within < 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
- Usage of GLP-1-based therapy (i.e., GLP-1 mono-agonists, GLP-1/GIP dual agonists, etc.) within 90 days prior to screening or during screening, or intent to initiate during the study period
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description sefaxersen (RO7434656) sefaxersen (RO7434656) Participants will receive subcutaneous (SC) doses of sefaxersen (RO7434656) on Days 1, 15, and 29 followed by once every 4 weeks until Week 105. Participants may be eligible to switch to open-label treatment after Week 105 at the investigator's discretion until up to 1 year after the common-close timepoint, the date when the last participant completes the Week 105 assessment, withdraws, or is discontinued from the study. Placebo Placebo Participants will receive SC doses of sefaxersen (RO7434656) matching placebo on Days 1, 15, and 29 followed by once every 4 weeks until Week 105. Participants may be eligible to switch to open-label treatment after Week 105 at the investigator's discretion until up to 1 year after the common-close timepoint, the date when the last participant completes the Week 105 assessment, withdraws, or is discontinued from the study.
- Primary Outcome Measures
Name Time Method Change From Baseline in the Urine Protein-to-Creatinine Ratio (UPCR) at Week 37 Baseline, Week 37 UPCR will be assessed in urine sampled over 24 hours.
- Secondary Outcome Measures
Name Time Method Estimated Glomerular Filtration Rate (eGFR) Slope at Week 105 from Baseline 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 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 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) Up to approximately 7 years Plasma Concentration of sefaxersen Up to approximately 7 years
Trial Locations
- Locations (177)
Hopital Bichat - Claude Bernard AP-HP
🇫🇷Paris, France
Hôpital de Rangueil
🇫🇷Toulouse, France
Hospital Universitario La Paz - PPDS
🇪🇸Madrid, Spain
Universitatsklinikum der RWTH Aachen
🇩🇪Aachen, Germany
Klinikum Koln-Merheim
🇩🇪Köln, Germany
Hopital Henri Mondor
🇫🇷Creteil, France
UAB Nephrology Research Clinic
🇺🇸Birmingham, Alabama, United States
Sunrise Medical Management LLC
🇺🇸Surprise, Arizona, United States
Tucson Neuroscience Research - M3 WR
🇺🇸Tucson, Arizona, United States
Southern California Medical Research Center
🇺🇸La Palma, California, United States
Academic Medical Research Institute - Los Angeles
🇺🇸Los Angeles, California, United States
UCLA University of California Los Angeles
🇺🇸Los Angeles, California, United States
North America Research Institute-San Dimas
🇺🇸San Dimas, California, United States
Hope Clinic & Research Center
🇺🇸Hialeah, Florida, United States
LCC Medical Research - Miami - ClinEdge - PPDS
🇺🇸Miami, Florida, United States
L&C Professional Medical Research Institute
🇺🇸W. Miami, Florida, United States
Cowry Medical Group LLC
🇺🇸Acworth, Georgia, United States
Care Institute Idaho Kidney Institute
🇺🇸Chubbuck, Idaho, United States
Nephrology Associates of Northern Illinois
🇺🇸Hinsdale, Illinois, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Massachussets General Hospital
🇺🇸Boston, Massachusetts, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Sierra Nevada Nephrology Consultants
🇺🇸Reno, Nevada, United States
NYU Langone Nephrology Associates - Mineola
🇺🇸Mineola, New York, United States
North Carolina Nephrology, PA
🇺🇸Raleigh, North Carolina, United States
Ohio State University Wexner Medical Center - Outpatient Care East
🇺🇸Columbus, Ohio, United States
Kidney and Hypertension Center
🇺🇸Roseburg, Oregon, United States
Global Medical Research - M3 WR
🇺🇸Dallas, Texas, United States
Texas Kidney Institute - Dallas
🇺🇸Dallas, Texas, 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
Revival Research Corporation - Sherman - ClinEdge - PPDS
🇺🇸Sherman, Texas, United States
Nephrology Associates of Northern Virginia Inc
🇺🇸Fairfax, Virginia, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Milwaukee Nephrologists, Sc
🇺🇸Wauwatosa, Wisconsin, United States
Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Consultorios Médicos Dr. Doreski
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Sanatorio Mayo Privado
🇦🇷Cordoba, Argentina
Sanatorio Allende
🇦🇷Cordoba, Argentina
Instituto Medico de la Fundacion Estudios Clinicos
🇦🇷Rosario, Argentina
Nepean Hospital
🇦🇺Kingswood, New South Wales, Australia
St George Hospital
🇦🇺Kogarah, New South Wales, Australia
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Sunshine Hospital
🇦🇺St Albans, Victoria, Australia
Santa Casa de Misericordia de Belo Horizonte - PPDS
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Freire Pesquisa Clinica
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Hospital de Clinicas de Porto Alegre HCPA PPDS
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Centro de Pesquisa Clinica da Fundação Pró Rim
🇧🇷Joinville, Santa Catarina, Brazil
Faculdade de Medicina da Universidade de Sao Paulo
🇧🇷Sao Paulo, São Paulo, Brazil
Hospital Do Rim E Hipertensao Fundacao Oswaldo Ramos
🇧🇷Sao Paulo, São Paulo, Brazil
Instituto D?Or Pesquisa e Ensino - Hospital Gloria D?Or
🇧🇷Rio de Janeiro, Brazil
Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
Cape Breton Regional Hospital
🇨🇦Sydney, Nova Scotia, Canada
Hopital Tenon
🇫🇷Paris, France
London Health Sciences Centre · Victoria Hospital
🇨🇦London, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier Universitaire de Quebec
🇨🇦Quebec, Canada
Beijing Friendship Hospital, Capital Medical University - PPDS
🇨🇳Beijing, Beijing, China
Peking University First Hospital
🇨🇳Beijing City, China
Peking University People's Hospital
🇨🇳Beijing, 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
Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
🇨🇳Hangzhou City, China
Zhejiang Provincial People?s Hospital
🇨🇳Hangzhou, China
The Second Affiliated Hospital of Nanchang University
🇨🇳Nanchang City, China
The Second Affiliated Hospital of Nanjing Medical University
🇨🇳Nanjing, China
Ningbo No.2 Hospital
🇨🇳Ningbo City, China
Ruijin Hospital Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai City, China
Xinhua Hospital Affiliated To Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, China
Shenzhen People's Hospital
🇨🇳Shenzhen City, China
The University of Hong Kong - Shenzhen Hospital
🇨🇳Shenzhen City, China
The Second Affiliated Hospital of Soochow University
🇨🇳Suzhou, China
Renmin Hospital of Wuhan University
🇨🇳Wuhan, 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, China
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
Centre Hospitalier
🇫🇷Annonay, France
CHU Boulogne sur Mer
🇫🇷Boulogne Sur Mer, France
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
🇩🇪Mainz, Germany
University General Hospital of Heraklion
🇬🇷Heraklion, Greece
Venizeleio General Hospital of Heraklion
🇬🇷Irakleio Kritis, Greece
University General Hospital of Patras
🇬🇷Patra, Greece
Ippokratio General Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Azienda Ospedaliera Universitaria Federico II
🇮🇹Napoli, Campania, Italy
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi-Via Massarenti
🇮🇹Bologna, Emilia-Romagna, Italy
Fondazione Policlinico Universitario A Gemelli
🇮🇹Roma, Lazio, Italy
Ospedale Policlinico San Martino
🇮🇹Genova, Liguria, Italy
IRCCS Pavia - Istituti Clinici Scientifici Maugeri Spa ? Società Benefit
🇮🇹Pavia, Lombardia, Italy
Ospedale San Giovanni Bosco
🇮🇹Torino, Piemonte, Italy
Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari
🇮🇹Bari, Puglia, Italy
Fujita Health University Hospital
🇯🇵Aichi, Japan
Hirosaki University Hospital
🇯🇵Aomori, Japan
Juntendo University Urayasu Hospital
🇯🇵Chiba, Japan
University of Yamanashi Hospital
🇯🇵Chuo, Japan
Matsuyama Red Cross Hospital
🇯🇵Ehime, Japan
Japanese Red Cross Fukuoka Hospital
🇯🇵Fukuoka, Japan
Hiroshima University Hospital
🇯🇵Hiroshima, Japan
Hokkaido University Hospital
🇯🇵Hokkaido, Japan
Tokyo Medical University Ibaraki Medical Center
🇯🇵Inashiki-Gun, Japan
Kanazawa Medical University Hospital
🇯🇵Ishikawa, Japan
Iwate Medical University Hospital
🇯🇵Iwate, Japan
Nara Medical University Hospital
🇯🇵Kashihara, Japan
Kumamoto University Hospital
🇯🇵Kumamoto, Japan
Tohoku University Hospital
🇯🇵Miyagi, Japan
Kyoto City Hospital
🇯🇵Nakagyo-ku, Japan
Nara Prefecture General Medical Center
🇯🇵Nara, Japan
Hyogo Prefectural Nishinomiya Hospital
🇯🇵Nishinomiya, Japan
Okayama University Hospital
🇯🇵Okayama-Shi Kita-Ku, Japan
National Hospital Organization Okayama Medical Center
🇯🇵Okayama, Japan
University of the Ryukyus Hospital
🇯🇵Okinawa, Japan
Saitama Medical University Hospital
🇯🇵Saitama, Japan
Osaka University Hospital
🇯🇵Suita, Japan
Jichi Medical University Hospital
🇯🇵Tochigi, Japan
Tokushima University Hospital
🇯🇵Tokushima, Japan
The Jikei University Hospital
🇯🇵Tokyo, Japan
Juntendo University Hospital
🇯🇵Tokyo, Japan
Tokyo Women's Medical University Hospital
🇯🇵Tokyo, Japan
Juntendo University Nerima Hospital, department of renal and hypertension
🇯🇵Tokyo, Japan
University of Tsukuba Hospital
🇯🇵Tsukuba, Japan
Yamaguchi University Hospital
🇯🇵Ube, Japan
Hallym University Sacred Heart Hospital
🇰🇷Anyang-si, Korea, Republic of
Soon Chun Hyang University Hospital Bucheon
🇰🇷Bucheon-si,, Korea, Republic of
Chungbuk National University Hospital
🇰🇷Cheongju si, Korea, Republic of
Ajou University Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
CHA Bundang Medical Center, CHA University
🇰🇷Seongnam-si, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Konkuk University Medical Center
🇰🇷Seoul, Korea, Republic of
Gangdong Kyung Hee University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
SMG-SNU Boramae Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Kuala Lumpur
🇲🇾Kuala Lumpur, FED. Territory OF Kuala Lumpur, Malaysia
University Malaya Medical Centre
🇲🇾Kuala Lumpur, FED. Territory OF Kuala Lumpur, Malaysia
Hospital Tengku Ampuan Afzan
🇲🇾Kuantan, Pahang, Malaysia
Hospital Seri Manjung
🇲🇾Seri Manjong, Pahang, Malaysia
Taiping Hospital
🇲🇾Taiping, Perak, Malaysia
Hospital Sibu
🇲🇾Sibu, Sarawak, Malaysia
Hospital Ampang
🇲🇾Ampang, Malaysia
Miri Hospital
🇲🇾Miri, Malaysia
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
🇲🇽Barrio Belisario Domínguez Secc XVI, Mexico CITY (federal District), Mexico
Centro de Investigacion Clinica Chapultepec S. A. de C. V.
🇲🇽Morelia, Michoacan, Mexico
Instituto Mexicano de Trasplantes
🇲🇽Cuernavaca, Morelos, Mexico
SCM Clinic - Prywatny Szpital Specjalistyczny
🇵🇱Kraków, Poland
SPZOZ Centralny Szpital Klin
🇵🇱Lodz, Poland
Szpital Kliniczny im. H.Swiecickiego UM w Poznaniu
🇵🇱Pozna?, Poland
Szpital Kliniczny Dzieciatka Jezus
🇵🇱Warszawa, Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
🇵🇱Wroc?aw, Poland
National University Hospital
🇸🇬Singapore, Singapore
Singapore General Hospital
🇸🇬Singapore, Singapore
Tan Tock Seng Hospital
🇸🇬Singapore, Singapore
Changi General Hospital
🇸🇬Singapore, Singapore
Hospital Universitari Arnau de Vilanova
🇪🇸Lleida, Lerida, Spain
Hospital Universitario Vall d'Hebron - PPDS
🇪🇸Barcelona, Spain
Hospital Ribera Polusa
🇪🇸Lugo, Spain
Hospital Universitario 12 De Octubre
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio - PPDS
🇪🇸Sevilla, Spain
Changhua Christian Hospital
🇨🇳Changhua, Taiwan
Chang Gung Medical Foundation
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
Far Eastern Memorial Hospital
🇨🇳Taipei, Taiwan
Chang Gung Memorial Hospital, Linkou
🇨🇳Taoyuan City, Taiwan
Taichung Veterans General Hospital
🇨🇳Xitun Dist., Taiwan
Mackay Memorial Hospital-Taipei branch
🇨🇳Zhongshan Dist., Taiwan
Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
Leicester General Hospital
🇬🇧Leicester, United Kingdom
Guys and St Thomas Hospital
🇬🇧London, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom
Churchill Hospital
🇬🇧Oxford, United Kingdom
Salford Royal Hospital
🇬🇧Salford, United Kingdom