Atrasentan in Patients With IgA Nephropathy
ALIGN
A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Atrasentan in Patients With IgA Nephropathy at Risk of Progressive Loss of Renal Function
1 other identifier
interventional
404
20 countries
135
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.
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 Dec 2020
Longer than P75 for phase_3
135 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
September 12, 2020
CompletedFirst Posted
Study publicly available on registry
October 5, 2020
CompletedStudy Start
First participant enrolled
December 11, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 18, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 18, 2026
October 15, 2024
October 1, 2024
6 years
September 12, 2020
October 10, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Double-blind period: Change in proteinuria
The change in urine protein:creatinine ratio (UPCR) from baseline to Week 36. (non-SGLT2i stratum)
Up to Week 36 or approximately 9 months
Open-label period: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)
Type, incidence, severity, seriousness, and relatedness of TEAEs.
From open-label baseline up to end of treatment visit, 48 weeks
Open-label period: Number of Subjects With Adverse Events of Special Interest (AESI) Including Events of Fluid Overload
Incidence, severity, seriousness, and relatedness AESIs.
From open-label baseline up to end of treatment visit, 48 weeks
Secondary Outcomes (8)
Double-blind period: Change in eGFR
Up to Week 136, 4 weeks post end of treatment
Double-blind period: Percent of subjects meeting the first composite endpoint
Up to approximately 2.6 years
Double-blind period: Percent of subjects meeting the second composite endpoint
Up to approximately 2.6 years
Double-blind period: Percent of subjects achieving reduction of proteinuria to < 1 g/day at Week 36
Baseline to Week 36
Double-blind period: Number of Subjects With TEAEs
From first dose of study drug up to 4 weeks post end of treatment in double-blind period, 136 weeks
- +3 more secondary outcomes
Study Arms (2)
Atrasentan
EXPERIMENTALDouble-blind Period: Once daily oral administration of 0.75 mg atrasentan for 132 weeks. Open-label Extension Period: Once daily oral administration of 0.75 mg atrasentan for 48 weeks after completion of 132 weeks on atrasentan or placebo.
Placebo
PLACEBO COMPARATORDouble-blind Period: Once daily oral administration of placebo for 132 weeks
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (135)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
Comprehensive Research Institute
Alhambra, California, 91754, United States
Kidney Disease Medical Group
Glendale, California, 91204, United States
Stanford University
Stanford, California, 93405, United States
University of Florida
Gainesville, Florida, 32610, United States
GA Nephrology Associates
Lawrenceville, Georgia, 30046, United States
NANI Research, LLC
Hinsdale, Illinois, 60521, United States
NANI Research, LLC
Fort Wayne, Indiana, 46804, United States
University of Louisville Physicians- Kidney Disease Program
Louisville, Kentucky, 40202, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Intermed Consultants
Minneapolis, Minnesota, 55404, United States
Pelican Point Dialysis - DaVita Clinical Research
Las Vegas, Nevada, 89129, United States
Capital District Renal Physicians
Clifton Park, New York, 12065, United States
Mountain Kidney and Hypertension Associates
Asheville, North Carolina, 28801, United States
Brookview Hills Research Associates, LLC
Winston-Salem, North Carolina, 27103, United States
Lehigh Valley Hospital
Bethlehem, Pennsylvania, 18017, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Liberty Research Center
Dallas, Texas, 75230, United States
El Paso Kidney Specialists
El Paso, Texas, 79925, United States
Nephrology Associates Of Northern Virginia
Fairfax, Virginia, 22033, United States
Swedish Health Services
Seattle, Washington, 98104, United States
Centro Médico Ce.Re.Ca
San Luis, San Luis Province, D5700CGR, Argentina
CEMIC
Buenos Aires, Argentina
Hospital Britanico de Buenos Aires
Buenos Aires, Argentina
Clinica de Nefrologia Urologia y Enf. Cardiovasculares
Santa Fe, Argentina
Royal North Shore Hospital
St Leonards, New South Wales, 2065, Australia
Melbourne Renal Research Group
Reservoir, Victoria, 3073, Australia
Sunshine Hospital
Saint Albans, Victoria, 3021, Australia
Box Hill Hospital
Box Hill, Australia
Royal Brisbane & Women's Hospital
Brisbane, Australia
Monash Medical Centre
Clayton, Australia
Renal Research
Gosford, Australia
Nepean Hospital
Kingswood, Australia
Instituto Pró-Renal Brasil
Curitiba, Paraná, Brazil
Hospital das Clínicas Universidade Federal de Minas Gerais - UFMG
Belo Horizonte, Brazil
Centro de Pesquisa Clinica do Brasil
Brasília, Brazil
Santa Casa de Misericordia de Porto Alegre
Porto Alegre, Brazil
Praxis Pesquisa Médica
Santo André, Brazil
Hospital das Clinicas da Faculdade de Medicina da USP
São Paulo, Brazil
Hospital do Rim Fundacao Oswaldo Ramos
São Paulo, Brazil
London Health Sciences Centre
London, Ontario, Canada
Stephen S. Chow Medicine Professionals
Toronto, Ontario, Canada
Dongguan Tungwah Hospital
Dongguan, Dongguan, China
Fujian Medical University Union Hospital
Fuzhou, Fujian, 350001, China
The First A ffliated Hospital of Baotou Medical College, Inner Mangolia University of Science and Technology
Baotou, Inner Mongolia Autonomou, 014010, China
Jiangsu Province Hospital
Nanjing, Jiangsu, 210029, China
The Affiliated Hospital of Nantong University
Nantong, Jiangsu, 226001, China
Renji Hospital Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai Municipality, China
People's Hospital of Sichuan Province
Chengdu, Sichuan, 610072, China
The First Affiliated Hospital Xinjiang Medical University
Ürümqi, Xinjiang Uygur, 830054, China
Peking University First Hospital
Beijing, 100034, China
Peking University People's Hospital
Beijing, 100044, China
The Second Hospital of Jilin University
Changchun, China
The Third Xiangya Hospital of Central South University
Changsha, China
West China Hospital, Sichuan University
Chengdu, China
The First Affiliated Hospital of Fujian Medical University
Fuzhou, China
Nanfang Hospital of Southern Medical University
Guangzhou, China
The Second Hospital of Anhui Medical University
Hefei, 230601, China
Shandong University - Qilu Hospital
Jinan, China
The First Affiliated Hospital of Nanchang University
Nanchang, China
Peking University Shenzhen Hospital
Shenzhen, 518036, China
Hospital Alma Mater de Antioquia
Medellín, Antioquia, 050010, Colombia
IPS Medicos Internistas de Caldas S.A.S
Manizales, Caldas Department, 170004, Colombia
CHU de Grenoble - Hopital Albert Michallon
Grenoble, France
CH Emile Roux
Le Puy-en-Velay, France
Hopital Necker
Paris, France
CHU Saint Etienne - Hopital Nord
Saint-Priest-en-Jarez, France
Centre Hospitalier Valenciennes
Valenciennes, France
St. Josefs-Hospital
Cloppenburg, Germany
Medizinische Hochschule Hannover
Hanover, Germany
Nephrologisches Zentrum Hoyerswerda
Hoyerswerda, Germany
Universitaetsklinikum Jena
Jena, Germany
Nephrologisches Zentrum Villingen-Schwenningen
Villingen-Schwenningen, Germany
Universitaetsklinikum Wuerzburg
Würzburg, Germany
Princess Margaret Hospital
Hong Kong, Hong Kong
The University of Hong Kong
Hong Kong, Hong Kong
Yan Chai Hospital
Hong Kong, Hong Kong
The Chinese University of Hong Kong
Shatin, Hong Kong
Government Medical College
Kozhikode, Kerala, 673008, India
Sahyadri Super Speciality Hospital
Pune, Maharashtra, 411004, India
Christian Medical College
Vellore, Tamil Nadu, 632004, India
Osmania General Hospital
Hyderabad, Telangana, 500012, India
Yashoda Hospital
Secunderabad, Telangana, 500003, India
Nil Ratan Sircar Medical College & Hospital
Kolkata, West Bengal, 700014, India
Fondazione IRCCS CA Granda Ospedale Maggiore Policlinico
Milan, Lombardy, 20122, Italy
Azienda Ospedaliero Universitaria San Martino
Genova, Italy
Seconda Università degli Studi di Napoli
Naples, Italy
ICS Maugeri SpA SB
Pavia, Italy
Kokura Memorial Hospital (Kokura Kinen Hospital)
Fukuoka, Japan
Kanazawa University Hospital
Kanazawa, Japan
Nara University
Kashihara, Japan
St. Marianna University (SMU) School of Medicine
Kawasaki, Japan
Niigata University
Niigata, Japan
Okayama University Hospital
Okayama, Japan
Osaka General Medical Center
Osaka, Japan
Dokkyo Medical University - Saitama Medical Center
Saitama, Japan
Showa University Hospital
Shinagawa-ku, Japan
Juntendo Nerima Hospital
Tokyo, Japan
Juntendo University Hospital, Tokyo
Tokyo, Japan
Fujita Health University Hospital
Toyoake, Japan
Juntendo University Urayasu Hospital
Urayasu, Japan
Waikato Hospital
Hamilton, New Zealand
Middlemore Clinical Trials
Papatoetoe, New Zealand
Samodzielny Publiczny ZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego
Lodz, Poland
Centrum Medyczne Medyk - Rzeszow
Rzeszów, Poland
Miedzyleski Szpital Specjalistyczny
Warsaw, Poland
Centro Hospitalar de Lisboa Ocidental EPE - Hospital Santa Cruz
Carnaxide, 2790-134, Portugal
Centro Hospitalar do Medio Tejo (CHMT), E.P.E.
Torres Novas, 2350-399, Portugal
Hallym University Medical Center
Anyang, South Korea
Chungnam National University Hospital
Daejeon, South Korea
Myongji Hospital
Gyeonggi-do, 10475, South Korea
Seoul National University Bundang Hospital
Gyeonggi-do, 13620, South Korea
Jeju National University Hospital
Jeju City, South Korea
CHA Bundang Medical Center, CHA University
Seongnam-si, South Korea
Korea University Anam Hospital
Seoul, South Korea
Kyung Hee University Hospital at Gangdong
Seoul, South Korea
Severance Hospital, Yonsei University Hospital
Seoul, South Korea
Fundacion Puigvert
Barcelona, Spain
Hospital Universitari Vall d'Hebron
Barcelona, Spain
Hospital Universitario 12 De Octubre
Madrid, Spain
Hospital de Sagunto
Sagunto, Spain
Hospital Universitario Virgen Macarena
Seville, Spain
H U Dr. Peset
Valencia, Spain
Changhua Christian Medical Foundation
Changhua, Taiwan
National Taiwan University Hospital Hsin-Chu Branch
Hsinchu, Taiwan
Far Eastern Memorial Hospital
New Taipei City, Taiwan
Taipei Medical University
New Taipei City, Taiwan
National Taiwan University Hospital
Taipei, Taiwan
North Bristol HNS Trust, Clinical Research Centre
Bristol, BS10 5NB, United Kingdom
Lister Hospital
Hertford, United Kingdom
Leicester General Hospital
Leicester, LE5 4PW, United Kingdom
King's College Hospital
London, SE5 9R6, United Kingdom
Guys Hospital
London, United Kingdom
Royal London Hospital
London, United Kingdom
Salford Royal
Salford, United Kingdom
Related Publications (1)
Heerspink HJL, Jardine M, Kohan DE, Lafayette RA, Levin A, Liew A, Zhang H, Lodha A, Gray T, Wang Y, Renfurm R, Barratt J; ALIGN Study Investigators. Atrasentan in Patients with IgA Nephropathy. N Engl J Med. 2025 Feb 6;392(6):544-554. doi: 10.1056/NEJMoa2409415. Epub 2024 Oct 25.
PMID: 39460694DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Masking Details
- Double-blind
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 12, 2020
First Posted
October 5, 2020
Study Start
December 11, 2020
Primary Completion (Estimated)
December 18, 2026
Study Completion (Estimated)
December 18, 2026
Last Updated
October 15, 2024
Record last verified: 2024-10
Data Sharing
- IPD Sharing
- Will not share