Clinical trial NCT04573478: Atrasentan in Patients With IgA Nephropathy
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Atrasentan in Patients With IgA Nephropathy at Risk of Progressive Loss of Renal Function
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: IgA Nephropathy
Immunoglobulin A Nephropathy
Keywords: Kidney Diseases
Kidney Disease, Chronic
Urologic Diseases
Glomerulonephritis
Glomerular Disease
Glomerulonephritis, IGA
Glomerulopathy
Immunoglobulin Disease
Lead sponsor: Chinook Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-10-05
Enrollment: 404
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 ALIGN Study is a phase 3, double-blind, placebo-controlled study to compare the efficacy and safety of atrasentan to placebo in patients with IgA nephropathy (IgAN) at risk of progressive loss of renal function.

Detailed description: Approximately 320 patients with biopsy-proven IgAN will be randomized to receive 0.75 mg atrasentan or placebo daily for 132 weeks. Subjects receive a maximally tolerated and stable dose of a RAS (renin-angiotensin system) inhibitor \[such as angiotensin converting enzyme inhibitor (ACEi) or angiotensin-receptor antagonist (ARB)\] as part of standard of care. An exception will be made for subjects who are unable to tolerate RAS inhibitor therapy.

Additional subjects receiving a stable dose of SGLT2i will be enrolled to the study. Enrollment in this SGLT2i stable stratum will be in accordance with local regulations in regions that prescribe SGLT2i and will be independent of the 320 subjects enrolled for the primary and secondary analyses.

The primary objective of the study is to evaluate the effect of atrasentan versus placebo on proteinuria as measured by UPCR. Secondary and tertiary objectives include evaluating the change in kidney function over time as measured by eGFR, safety and tolerability, as well as quality of life.

Subjects will have assessments of safety and efficacy over 2 ½ years. To facilitate study participation over this time period, where allowed by local regulations, options for remote study visits using telemedicine and home health may be offered.

Subjects who complete treatment through Week 132 and complete the double-blinded portion of the study may be eligible to enroll in the open label extension of the study to receive atrasentan 0.75 mg daily for up to 48 weeks.

Eligibility criteria: Inclusion Criteria:

Double-Blind period:

* Biopsy-proven IgA nephropathy.
* Receiving a maximally tolerated dose of RAS inhibitor therapy (ACEi or ARB) that has been stable for at least 12 weeks. Exceptions from this requirement will be made for subjects who are unable to tolerate RAS inhibitor therapy.
* Total urine protein ≥1 g/day as measured via 24-hour urine collection by central laboratory at Screening.
* eGFR of at least 30 mL/min/1.73 m\^2 at Screening based on the CKD-EPI equation.
* Willing and able to provide informed consent and comply with all study requirements.
* SGLT2i Stable Stratum Only - Receiving a stable dose of an SGLT2i (per Investigator choice) in addition to a maximally tolerated and optimized dose of a RAS inhibitor that has been stable for at least 12 weeks prior to Screening.
* All fertile men and WOCBP who engage in heterosexual intercourse must be willing to abide with highly effective forms of contraception, as specified in the protocol, throughout the study and for 1 month afterward. In WOCBP, use of contraceptive agents must have been started at least 1 month prior to Baseline.

Open-Label Period:

* Willing and able to provide informed consent and comply with all OL extension study visits and study procedures.
* Completed treatment through Week 132 and completed the Week 136 visit.
* All fertile men and WOCBP who engage in heterosexual intercourse must be willing to abide with highly effective forms of contraception, as specified in the protocol, throughout the study and for 1 month afterward. In WOCBP, use of contraceptive agents must have been continued after completing the double-blind portion of the study.

Exclusion Criteria:

Double-blind period:

* Concurrent diagnosis of another cause of chronic kidney disease including diabetic kidney disease or another primary glomerulopathy.
* Clinical diagnosis of nephrotic syndrome.
* BNP value of \> 200 pg/mL at Screening.
* Platelet count \<80,000 per μL at Screening.
* History of organ transplantation (subjects with history of corneal transplant are not excluded).
* Use of systemic immunosuppressant medications.
* Hemoglobin below 9 g/dL at Screening or prior history of blood transfusion for anemia within 3 months of Screening.

Open-label period:

* eGFR \< 25 mL/min/1.73m\^2 or evidence of rapidly decreasing eGFR, including unrecovered acute kidney injury or expected to require renal replacement therapy within 3 months
* BNP value of \> 200 pg/mL at OL Screening.
* Platelet count \< 80,000 per μL at OL Screening.
* Hemoglobin below 9 g/dL at OL screening or prior history of blood transfusion for anemia within 3 months of OL Screening.

Primary outcomes:
measure: Double-blind period: Change in proteinuria
timeFrame: Up to Week 36 or approximately 9 months
measure: Open-label period: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From open-label baseline up to end of treatment visit, 48 weeks
measure: Open-label period: Number of Subjects With Adverse Events of Special Interest (AESI) Including Events of Fluid Overload
timeFrame: From open-label baseline up to end of treatment visit, 48 weeks
Secondary outcomes:
measure: Double-blind period: Change in eGFR
timeFrame: Up to Week 136, 4 weeks post end of treatment
measure: Double-blind period: Percent of subjects meeting the first composite endpoint
timeFrame: Up to approximately 2.6 years
measure: Double-blind period: Percent of subjects meeting the second composite endpoint
timeFrame: Up to approximately 2.6 years
measure: Double-blind period: Percent of subjects achieving reduction of proteinuria to < 1 g/day at Week 36
timeFrame: Baseline to Week 36
measure: Double-blind period: Number of Subjects With TEAEs
timeFrame: From first dose of study drug up to 4 weeks post end of treatment in double-blind period, 136 weeks
measure: Double-blind period: Number of Subjects With AESI Including Events of Fluid Overload
timeFrame: From first dose of study drug up to 4 weeks post end of treatment in double-blind period, 136 weeks
measure: Open-label period: Change in proteinuria
timeFrame: Open-label Baseline to open-label Week 36
measure: Open-label period: Change in eGFR
timeFrame: Open-label Baseline to open-label Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Alhambra
country: United States
facility: Comprehensive Research Institute
state: California
city: Glendale
country: United States
facility: Kidney Disease Medical Group
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Lawrenceville
country: United States
facility: GA Nephrology Associates
state: Georgia
city: Hinsdale
country: United States
facility: NANI Research, LLC
state: Illinois
city: Fort Wayne
country: United States
facility: NANI Research, LLC
state: Indiana
city: Louisville
country: United States
facility: University of Louisville Physicians- Kidney Disease Program
state: Kentucky
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: Intermed Consultants
state: Minnesota
city: Las Vegas
country: United States
facility: Pelican Point Dialysis - DaVita Clinical Research
state: Nevada
city: Clifton Park
country: United States
facility: Capital District Renal Physicians
state: New York
city: Asheville
country: United States
facility: Mountain Kidney and Hypertension Associates
state: North Carolina
city: Winston-Salem
country: United States
facility: Brookview Hills Research Associates, LLC
state: North Carolina
city: Bethlehem
country: United States
facility: Lehigh Valley Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: Liberty Research Center
state: Texas
city: El Paso
country: United States
facility: El Paso Kidney Specialists
state: Texas
city: Fairfax
country: United States
facility: Nephrology Associates Of Northern Virginia
state: Virginia
city: Seattle
country: United States
facility: Swedish Health Services
state: Washington
city: Ciudad De San Luis
country: Argentina
facility: Centro Médico Ce.Re.Ca
state: San Luis
city: Buenos Aires
country: Argentina
facility: CEMIC
city: Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Santa Fe
country: Argentina
facility: Clinica de Nefrologia Urologia y Enf. Cardiovasculares
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Reservoir
country: Australia
facility: Melbourne Renal Research Group
state: Victoria
city: Saint Albans
country: Australia
facility: Sunshine Hospital
state: Victoria
city: Box Hill
country: Australia
facility: Box Hill Hospital
city: Brisbane
country: Australia
facility: Royal Brisbane & Women's Hospital
city: Clayton
country: Australia
facility: Monash Medical Centre
city: Gosford
country: Australia
facility: Renal Research
city: Kingswood
country: Australia
facility: Nepean Hospital
city: Curitiba
country: Brazil
facility: Instituto Pró-Renal Brasil
state: Paraná
city: Belo Horizonte
country: Brazil
facility: Hospital das Clínicas Universidade Federal de Minas Gerais - UFMG
city: Brasília
country: Brazil
facility: Centro de Pesquisa Clinica do Brasil
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericordia de Porto Alegre
city: Santo André
country: Brazil
facility: Praxis Pesquisa Médica
city: São Paulo
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina da USP
city: São Paulo
country: Brazil
facility: Hospital do Rim Fundacao Oswaldo Ramos
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Stephen S. Chow Medicine Professionals
state: Ontario
city: Dongguan
country: China
facility: Dongguan Tungwah Hospital
state: Dongguan
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Baotou
country: China
facility: The First A ffliated Hospital of Baotou Medical College, Inner Mangolia University of Science and Technology
state: Inner Mongolia Autonomou
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nantong
country: China
facility: The Affiliated Hospital of Nantong University
state: Jiangsu
city: Shanghai
country: China
facility: Renji Hospital Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Chengdu
country: China
facility: People's Hospital of Sichuan Province
state: Sichuan
city: Ürümqi
country: China
facility: The First Affiliated Hospital Xinjiang Medical University
state: Xinjiang
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Peking University People's Hospital
city: Changchun
country: China
facility: The Second Hospital of Jilin University
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
city: Jinan
country: China
facility: Shandong University - Qilu Hospital
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
city: Medellín
country: Colombia
facility: Hospital Alma Mater de Antioquia
state: Antioquia
city: Manizales
country: Colombia
facility: IPS Medicos Internistas de Caldas S.A.S
state: Caldas
city: Grenoble
country: France
facility: CHU de Grenoble - Hopital Albert Michallon
city: Le Puy-en-Velay
country: France
facility: CH Emile Roux
city: Paris
country: France
facility: Hopital Necker
city: Saint-Priest-en-Jarez
country: France
facility: CHU Saint Etienne - Hopital Nord
city: Valenciennes
country: France
facility: Centre Hospitalier Valenciennes
city: Cloppenburg
country: Germany
facility: St. Josefs-Hospital
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Hoyerswerda
country: Germany
facility: Nephrologisches Zentrum Hoyerswerda
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
city: Villingen-Schwenningen
country: Germany
facility: Nephrologisches Zentrum Villingen-Schwenningen
city: Würzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Hong Kong
country: Hong Kong
facility: Princess Margaret Hospital
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong
city: Hong Kong
country: Hong Kong
facility: Yan Chai Hospital
city: Shatin
country: Hong Kong
facility: The Chinese University of Hong Kong
city: Kozhikode
country: India
facility: Government Medical College
state: Kerala
city: Pune
country: India
facility: Sahyadri Super Speciality Hospital
state: Maharashtra
city: Vellore
country: India
facility: Christian Medical College
state: Tamil Nadu
city: Hyderabad
country: India
facility: Osmania General Hospital
state: Telangana
city: Secunderabad
country: India
facility: Yashoda Hospital
state: Telangana
city: Kolkata
country: India
facility: Nil Ratan Sircar Medical College & Hospital
state: West Bengal
city: Milano
country: Italy
facility: Fondazione IRCCS CA Granda Ospedale Maggiore Policlinico
state: Lombardia
city: Genova
country: Italy
facility: Azienda Ospedaliero Universitaria San Martino
city: Naples
country: Italy
facility: Seconda Università degli Studi di Napoli
city: Pavia
country: Italy
facility: ICS Maugeri SpA SB
city: Fukuoka
country: Japan
facility: Kokura Memorial Hospital (Kokura Kinen Hospital)
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
city: Kashihara
country: Japan
facility: Nara University
city: Kawasaki
country: Japan
facility: St. Marianna University (SMU) School of Medicine
city: Niigata
country: Japan
facility: Niigata University
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Osaka General Medical Center
city: Saitama
country: Japan
facility: Dokkyo Medical University - Saitama Medical Center
city: Shinagawa-ku
country: Japan
facility: Showa University Hospital
city: Tokyo
country: Japan
facility: Juntendo Nerima Hospital
city: Tokyo
country: Japan
facility: Juntendo University Hospital, Tokyo
city: Toyoake
country: Japan
facility: Fujita Health University Hospital
city: Urayasu
country: Japan
facility: Juntendo University Urayasu Hospital
city: Anyang
country: Korea, Republic of
facility: Hallym University Medical Center
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Myongji Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Jeju
country: Korea, Republic of
facility: Jeju National University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: CHA Bundang Medical Center, CHA University
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Papatoetoe
country: New Zealand
facility: Middlemore Clinical Trials
city: Rzeszów
country: Poland
facility: Centrum Medyczne Medyk - Rzeszow
city: Warszawa
country: Poland
facility: Miedzyleski Szpital Specjalistyczny
city: Łódź
country: Poland
facility: Samodzielny Publiczny ZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego
city: Carnaxide
country: Portugal
facility: Centro Hospitalar de Lisboa Ocidental EPE - Hospital Santa Cruz
city: Torres Novas
country: Portugal
facility: Centro Hospitalar do Medio Tejo (CHMT), E.P.E.
city: Barcelona
country: Spain
facility: Fundacion Puigvert
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario 12 De Octubre
city: Sagunto
country: Spain
facility: Hospital de Sagunto
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: H U Dr. Peset
city: Changhua
country: Taiwan
facility: Changhua Christian Medical Foundation
city: Hsinchu
country: Taiwan
facility: National Taiwan University Hospital Hsin-Chu Branch
city: New Taipei City
country: Taiwan
facility: Far Eastern Memorial Hospital
city: New Taipei City
country: Taiwan
facility: Taipei Medical University
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Bristol
country: United Kingdom
facility: North Bristol HNS Trust, Clinical Research Centre
city: Hertford
country: United Kingdom
facility: Lister Hospital
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Guys Hospital
city: London
country: United Kingdom
facility: Royal London Hospital
city: Salford
country: United Kingdom
facility: Salford Royal
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: