Clinical trial NCT05797610: A Study to Evaluate the Efficacy and Safety of Sefaxersen (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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Primary IgA Nephropathy
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2023-04-04
Enrollment: 428
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change From Baseline in the Urine Protein-to-Creatinine Ratio (UPCR) at Week 37
timeFrame: Baseline, Week 37
Secondary outcomes:
measure: Estimated Glomerular Filtration Rate (eGFR) Slope at Week 105 from Baseline
timeFrame: Baseline, Week 105
measure: Time to the Composite Kidney Failure Endpoint
timeFrame: Up to approximately 7 years
measure: Change From Baseline in Fatigue at Week 105
timeFrame: Baseline, Week 105
measure: Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 7 years
measure: Plasma Concentration of sefaxersen
timeFrame: Up to approximately 7 years
Other outcomes:
measure: 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
timeFrame: Baseline, Week 105
Locations:
city: Birmingham
country: United States
facility: UAB Nephrology Research Clinic
state: Alabama
city: Surprise
country: United States
facility: Sunrise Medical Management LLC
state: Arizona
city: Tucson
country: United States
facility: Tucson Neuroscience Research - M3 WR
state: Arizona
city: La Palma
country: United States
facility: Southern California Medical Research Center
state: California
city: Los Angeles
country: United States
facility: Academic Medical Research Institute - Los Angeles
state: California
city: Los Angeles
country: United States
facility: UCLA University of California Los Angeles
state: California
city: San Dimas
country: United States
facility: North America Research Institute-San Dimas
state: California
city: Hialeah
country: United States
facility: Hope Clinic & Research Center
state: Florida
city: Miami
country: United States
facility: LCC Medical Research - Miami - ClinEdge - PPDS
state: Florida
city: W. Miami
country: United States
facility: L&C Professional Medical Research Institute
state: Florida
city: Acworth
country: United States
facility: Cowry Medical Group LLC
state: Georgia
city: Chubbuck
country: United States
facility: Care Institute Idaho Kidney Institute
state: Idaho
city: Hinsdale
country: United States
facility: Nephrology Associates of Northern Illinois
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Boston
country: United States
facility: Massachussets General Hospital
state: Massachusetts
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Reno
country: United States
facility: Sierra Nevada Nephrology Consultants
state: Nevada
city: Mineola
country: United States
facility: NYU Langone Nephrology Associates - Mineola
state: New York
city: Raleigh
country: United States
facility: North Carolina Nephrology, PA
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center - Outpatient Care East
state: Ohio
city: Roseburg
country: United States
facility: Kidney and Hypertension Center
state: Oregon
city: Dallas
country: United States
facility: Global Medical Research - M3 WR
state: Texas
city: Dallas
country: United States
facility: Texas Kidney Institute - Dallas
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions
state: Texas
city: Houston
country: United States
facility: Prolato Clinical Research Center
state: Texas
city: Katy
country: United States
facility: R & H Clinical Research
state: Texas
city: Sherman
country: United States
facility: Revival Research Corporation - Sherman - ClinEdge - PPDS
state: Texas
city: Fairfax
country: United States
facility: Nephrology Associates of Northern Virginia Inc
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Wauwatosa
country: United States
facility: Milwaukee Nephrologists, Sc
state: Wisconsin
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Consultorios Médicos Dr. Doreski
city: Cordoba
country: Argentina
facility: Sanatorio Mayo Privado
city: Cordoba
country: Argentina
facility: Sanatorio Allende
city: Rosario
country: Argentina
facility: Instituto Medico de la Fundacion Estudios Clinicos
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: St Albans
country: Australia
facility: Sunshine Hospital
state: Victoria
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte - PPDS
state: Minas Gerais
city: Belo Horizonte
country: Brazil
facility: Freire Pesquisa Clinica
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre HCPA PPDS
state: Rio Grande Do Sul
city: Joinville
country: Brazil
facility: Centro de Pesquisa Clinica da Fundação Pró Rim
state: Santa Catarina
city: Sao Paulo
country: Brazil
facility: Faculdade de Medicina da Universidade de Sao Paulo
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Do Rim E Hipertensao Fundacao Oswaldo Ramos
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Instituto D?Or Pesquisa e Ensino - Hospital Gloria D?Or
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Sydney
country: Canada
facility: Cape Breton Regional Hospital
state: Nova Scotia
city: London
country: Canada
facility: London Health Sciences Centre · Victoria Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Montreal General Hospital
state: Quebec
city: Quebec
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University - PPDS
state: Beijing
city: Beijing City
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Peking University People's Hospital
city: Changzhou
country: China
facility: Changzhou First People's Hospital
city: Chengdu City
country: China
facility: Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
city: Guangzhou City
country: China
facility: Guangdong Provincial People's Hospital
city: Hangzhou City
country: China
facility: Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
city: Hangzhou
country: China
facility: Zhejiang Provincial People?s Hospital
city: Nanchang City
country: China
facility: The Second Affiliated Hospital of Nanchang University
city: Nanjing
country: China
facility: The Second Affiliated Hospital of Nanjing Medical University
city: Ningbo City
country: China
facility: Ningbo No.2 Hospital
city: Shanghai City
country: China
facility: Ruijin Hospital Shanghai Jiaotong University School of Medicine
city: Shanghai
country: China
facility: Xinhua Hospital Affiliated To Shanghai Jiaotong University School of Medicine
city: Shenzhen City
country: China
facility: Shenzhen People's Hospital
city: Shenzhen City
country: China
facility: The University of Hong Kong - Shenzhen Hospital
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
city: Xi'an City
country: China
facility: The First Affiliated Hospital of Xian Jiao Tong University
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
city: Zhenjiang
country: China
facility: Affiliated Hospital of Jiangsu University
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Annonay
country: France
facility: Centre Hospitalier
city: Boulogne Sur Mer
country: France
facility: CHU Boulogne sur Mer
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Paris
country: France
facility: Hopital Tenon
city: Paris
country: France
facility: Hopital Bichat - Claude Bernard AP-HP
city: Toulouse
country: France
facility: Hôpital de Rangueil
city: Aachen
country: Germany
facility: Universitatsklinikum der RWTH Aachen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Köln
country: Germany
facility: Klinikum Koln-Merheim
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion
city: Irakleio Kritis
country: Greece
facility: Venizeleio General Hospital of Heraklion
city: Patra
country: Greece
facility: University General Hospital of Patras
city: Thessaloniki
country: Greece
facility: Ippokratio General Hospital of Thessaloniki
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
state: Campania
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi-Via Massarenti
state: Emilia-Romagna
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli
state: Lazio
city: Genova
country: Italy
facility: Ospedale Policlinico San Martino
state: Liguria
city: Pavia
country: Italy
facility: IRCCS Pavia - Istituti Clinici Scientifici Maugeri Spa ? Società Benefit
state: Lombardia
city: Torino
country: Italy
facility: Ospedale San Giovanni Bosco
state: Piemonte
city: Bari
country: Italy
facility: Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari
state: Puglia
city: Aichi
country: Japan
facility: Fujita Health University Hospital
city: Aomori
country: Japan
facility: Hirosaki University Hospital
city: Chiba
country: Japan
facility: Juntendo University Urayasu Hospital
city: Chuo
country: Japan
facility: University of Yamanashi Hospital
city: Ehime
country: Japan
facility: Matsuyama Red Cross Hospital
city: Fukuoka
country: Japan
facility: Japanese Red Cross Fukuoka Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Inashiki-Gun
country: Japan
facility: Tokyo Medical University Ibaraki Medical Center
city: Ishikawa
country: Japan
facility: Kanazawa Medical University Hospital
city: Iwate
country: Japan
facility: Iwate Medical University Hospital
city: Kashihara
country: Japan
facility: Nara Medical University Hospital
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Miyagi
country: Japan
facility: Tohoku University Hospital
city: Nakagyo-ku
country: Japan
facility: Kyoto City Hospital
city: Nara
country: Japan
facility: Nara Prefecture General Medical Center
city: Nishinomiya
country: Japan
facility: Hyogo Prefectural Nishinomiya Hospital
city: Okayama-Shi Kita-Ku
country: Japan
facility: Okayama University Hospital
city: Okayama
country: Japan
facility: National Hospital Organization Okayama Medical Center
city: Okinawa
country: Japan
facility: University of the Ryukyus Hospital
city: Saitama
country: Japan
facility: Saitama Medical University Hospital
city: Suita
country: Japan
facility: Osaka University Hospital
city: Tochigi
country: Japan
facility: Jichi Medical University Hospital
city: Tokushima
country: Japan
facility: Tokushima University Hospital
city: Tokyo
country: Japan
facility: The Jikei University Hospital
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Tokyo
country: Japan
facility: Tokyo Women's Medical University Hospital
city: Tokyo
country: Japan
facility: Juntendo University Nerima Hospital, department of renal and hypertension
city: Tsukuba
country: Japan
facility: University of Tsukuba Hospital
city: Ube
country: Japan
facility: Yamaguchi University Hospital
city: Anyang-si
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
city: Bucheon-si,
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Bucheon
city: Cheongju si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Ajou University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: CHA Bundang Medical Center, CHA University
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangdong Kyung Hee University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: SMG-SNU Boramae Medical Center
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
state: FED. Territory OF Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
state: FED. Territory OF Kuala Lumpur
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan
state: Pahang
city: Seri Manjong
country: Malaysia
facility: Hospital Seri Manjung
state: Pahang
city: Taiping
country: Malaysia
facility: Taiping Hospital
state: Perak
city: Sibu
country: Malaysia
facility: Hospital Sibu
state: Sarawak
city: Ampang
country: Malaysia
facility: Hospital Ampang
city: Miri
country: Malaysia
facility: Miri Hospital
city: Barrio Belisario Domínguez Secc XVI
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
state: Mexico CITY (federal District)
city: Morelia
country: Mexico
facility: Centro de Investigacion Clinica Chapultepec S. A. de C. V.
state: Michoacan
city: Cuernavaca
country: Mexico
facility: Instituto Mexicano de Trasplantes
state: Morelos
city: Monterrey
country: Mexico
facility: Christus Latam Hub Center Of Excellence & Innovation
state: Nuevo LEON
city: Aguascalientes
country: Mexico
facility: Centenario Hospital Miguel Hidalgo
city: Kraków
country: Poland
facility: SCM Clinic - Prywatny Szpital Specjalistyczny
city: Lodz
country: Poland
facility: SPZOZ Centralny Szpital Klin
city: Pozna?
country: Poland
facility: Szpital Kliniczny im. H.Swiecickiego UM w Poznaniu
city: Warszawa
country: Poland
facility: Szpital Kliniczny Dzieciatka Jezus
city: Wroc?aw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Singapore
country: Singapore
facility: Changi General Hospital
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
state: Lerida
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Lugo
country: Spain
facility: Hospital Ribera Polusa
city: Madrid
country: Spain
facility: Hospital Universitario 12 De Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz - PPDS
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio - PPDS
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Taoyuan City
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou
city: Xitun Dist.
country: Taiwan
facility: Taichung Veterans General Hospital
city: Zhongshan Dist.
country: Taiwan
facility: Mackay Memorial Hospital-Taipei branch
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
city: London
country: United Kingdom
facility: Guys and St Thomas Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: