Atrasentan in Patients With IgA Nephropathy
- Conditions
- IgA NephropathyImmunoglobulin A Nephropathy
- Interventions
- Drug: Placebo
- Registration Number
- NCT04573478
- Lead Sponsor
- Chinook Therapeutics, Inc.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 404
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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Double-blind Period: Once daily oral administration of placebo for 132 weeks Atrasentan Atrasentan Double-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.
- Primary Outcome Measures
Name Time Method Double-blind period: Change in proteinuria Up to Week 36 or approximately 9 months The change in urine protein:creatinine ratio (UPCR) from baseline to Week 36. (non-SGLT2i stratum)
Open-label period: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) From open-label baseline up to end of treatment visit, 48 weeks Type, incidence, severity, seriousness, and relatedness of TEAEs.
Open-label period: Number of Subjects With Adverse Events of Special Interest (AESI) Including Events of Fluid Overload From open-label baseline up to end of treatment visit, 48 weeks Incidence, severity, seriousness, and relatedness AESIs.
- Secondary Outcome Measures
Name Time Method Double-blind period: Change in eGFR Up to Week 136, 4 weeks post end of treatment Change from Baseline to final study visit (Week 136, 4 weeks post end of treatment) using the chronic kidney disease-epidemiology collaboration (CKD-EPI) creatinine equation (non-SGLT2i stratum)
Open-label period: Change in proteinuria Open-label Baseline to open-label Week 36 Change in UPCR based on 24-hour urine collection.
Open-label period: Change in eGFR Open-label Baseline to open-label Week 52 Change from open-label Baseline to open-label Week 52 using the CKD-EPI creatinine equation.
Double-blind period: Percent of subjects meeting the first composite endpoint Up to approximately 2.6 years Percent of subjects in the non-SGLT2i stratum meeting the composite endpoint of experiencing at least one of the following during the study:
* At least a 30% reduction in eGFR sustained for at least 30 days
* eGFR \<15 mL/min/1.73m\^2, sustained for at least 30 days
* Chronic dialysis ≥30 days
* Kidney transplantation
* All-cause mortalityDouble-blind period: Percent of subjects meeting the second composite endpoint Up to approximately 2.6 years Percent of subjects in the non-SGLT2i stratum meeting the composite endpoint of experiencing at least one of the following during the study:
* At least a 40% reduction in eGFR sustained for at least 30 days
* eGFR \<15 mL/min/1.73m\^2, sustained for at least 30 days
* Chronic dialysis ≥30 days
* Kidney transplantation
* All-cause mortalityDouble-blind period: Percent of subjects achieving reduction of proteinuria to < 1 g/day at Week 36 Baseline to Week 36 Percentage of subjects with reduction of proteinuria to \< 1 g/day and a 25% decrease in total urine protein from Baseline (non-SGLT2i stratum).
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 Type, incidence, severity, seriousness, and relatedness of TEAEs.
Double-blind period: Number of Subjects With AESI Including Events of Fluid Overload From first dose of study drug up to 4 weeks post end of treatment in double-blind period, 136 weeks Incidence, severity, seriousness, and relatedness AESIs.
Trial Locations
- Locations (134)
Liberty Research Center
🇺🇸Dallas, Texas, United States
The First Affiliated Hospital of Fujian Medical University
🇨🇳Fuzhou, China
Peking University People's Hospital
🇨🇳Beijing, China
Nanfang Hospital of Southern Medical University
🇨🇳Guangzhou, China
Centro Médico Ce.Re.Ca
🇦🇷Ciudad De San Luis, San Luis, Argentina
Capital District Renal Physicians
🇺🇸Clifton Park, New York, United States
Swedish Health Services
🇺🇸Seattle, Washington, United States
Hospital Britanico de Buenos Aires
🇦🇷Buenos Aires, Argentina
Nephrology Associates Of Northern Virginia
🇺🇸Fairfax, Virginia, United States
Peking University Shenzhen Hospital
🇨🇳Shenzhen, China
People's Hospital of Sichuan Province
🇨🇳Chengdu, Sichuan, China
The First Affiliated Hospital Xinjiang Medical University
🇨🇳Ürümqi, Xinjiang, China
Shandong University - Qilu Hospital
🇨🇳Jinan, China
Universitaetsklinikum Wuerzburg
🇩🇪Würzburg, Germany
Praxis Pesquisa Médica
🇧🇷Santo André, Brazil
St. Josefs-Hospital
🇩🇪Cloppenburg, Germany
Mountain Kidney and Hypertension Associates
🇺🇸Asheville, North Carolina, United States
Brookview Hills Research Associates, LLC
🇺🇸Winston-Salem, North Carolina, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of Louisville Physicians- Kidney Disease Program
🇺🇸Louisville, Kentucky, United States
Intermed Consultants
🇺🇸Minneapolis, Minnesota, United States
Centro de Pesquisa Clinica do Brasil
🇧🇷Brasília, Brazil
Kidney Disease Medical Group
🇺🇸Glendale, California, United States
Comprehensive Research Institute
🇺🇸Alhambra, California, United States
GA Nephrology Associates
🇺🇸Lawrenceville, Georgia, United States
NANI Research, LLC
🇺🇸Fort Wayne, Indiana, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Lehigh Valley Hospital
🇺🇸Bethlehem, Pennsylvania, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
El Paso Kidney Specialists
🇺🇸El Paso, Texas, United States
Box Hill Hospital
🇦🇺Box Hill, Australia
Royal North Shore Hospital
🇦🇺St. Leonards, New South Wales, Australia
Melbourne Renal Research Group
🇦🇺Reservoir, Victoria, Australia
Royal Brisbane & Women's Hospital
🇦🇺Brisbane, Australia
Monash Medical Centre
🇦🇺Clayton, Australia
Renal Research
🇦🇺Gosford, Australia
Nepean Hospital
🇦🇺Kingswood, Australia
Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, Brazil
Hospital das Clínicas Universidade Federal de Minas Gerais - UFMG
🇧🇷Belo Horizonte, Brazil
Instituto Pró-Renal Brasil
🇧🇷Curitiba, Paraná, Brazil
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Hospital das Clinicas da Faculdade de Medicina da USP
🇧🇷São Paulo, Brazil
Hospital do Rim Fundacao Oswaldo Ramos
🇧🇷São Paulo, Brazil
Dongguan Tungwah Hospital
🇨🇳Dongguan, Dongguan, China
Stephen S. Chow Medicine Professionals
🇨🇦Toronto, Ontario, Canada
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
The Affiliated Hospital of Nantong University
🇨🇳Nantong, Jiangsu, China
Jiangsu Province Hospital
🇨🇳Nanjing, Jiangsu, China
The First A ffliated Hospital of Baotou Medical College, Inner Mangolia University of Science and Technology
🇨🇳Baotou, Inner Mongolia Autonomou, China
Renji Hospital Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, Shanghai, China
The Third Xiangya Hospital of Central South University
🇨🇳Changsha, China
The Second Hospital of Jilin University
🇨🇳Changchun, China
West China Hospital, Sichuan University
🇨🇳Chengdu, China
The Second Hospital of Anhui Medical University
🇨🇳Hefei, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, China
CH Emile Roux
🇫🇷Le Puy-en-Velay, France
CHU de Grenoble - Hopital Albert Michallon
🇫🇷Grenoble, France
Hopital Necker
🇫🇷Paris, France
CHU Saint Etienne - Hopital Nord
🇫🇷Saint-Priest-en-Jarez, France
Centre Hospitalier Valenciennes
🇫🇷Valenciennes, France
Universitaetsklinikum Jena
🇩🇪Jena, Germany
Nephrologisches Zentrum Hoyerswerda
🇩🇪Hoyerswerda, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Nephrologisches Zentrum Villingen-Schwenningen
🇩🇪Villingen-Schwenningen, Germany
Princess Margaret Hospital
🇭🇰Hong Kong, Hong Kong
Government Medical College
🇮🇳Kozhikode, Kerala, India
The Chinese University of Hong Kong
🇭🇰Shatin, Hong Kong
Sahyadri Super Speciality Hospital
🇮🇳Pune, Maharashtra, India
Osmania General Hospital
🇮🇳Hyderabad, Telangana, India
Yashoda Hospital
🇮🇳Secunderabad, Telangana, India
Fondazione IRCCS CA Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Lombardia, Italy
Nil Ratan Sircar Medical College & Hospital
🇮🇳Kolkata, West Bengal, India
St. Marianna University (SMU) School of Medicine
🇯🇵Kawasaki, Japan
Azienda Ospedaliero Universitaria San Martino
🇮🇹Genova, Italy
Seconda Università degli Studi di Napoli
🇮🇹Naples, Italy
ICS Maugeri SpA SB
🇮🇹Pavia, Italy
Nara University
🇯🇵Kashihara, Japan
Kokura Memorial Hospital (Kokura Kinen Hospital)
🇯🇵Fukuoka, Japan
Kanazawa University Hospital
🇯🇵Kanazawa, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Niigata University
🇯🇵Niigata, Japan
Showa University Hospital
🇯🇵Shinagawa-ku, Japan
Fujita Health University Hospital
🇯🇵Toyoake, Japan
Juntendo Nerima Hospital
🇯🇵Tokyo, Japan
Hallym University Medical Center
🇰🇷Anyang, Korea, Republic of
Juntendo University Urayasu Hospital
🇯🇵Urayasu, Japan
Myongji Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Chungnam National University Hospital
🇰🇷Daejeon, Korea, Republic of
CHA Bundang Medical Center, CHA University
🇰🇷Seongnam-si, Korea, Republic of
Jeju National University Hospital
🇰🇷Jeju, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Hospital
🇰🇷Seoul, Korea, Republic of
Waikato Hospital
🇳🇿Hamilton, New Zealand
Middlemore Clinical Trials
🇳🇿Papatoetoe, New Zealand
Kyung Hee University Hospital at Gangdong
🇰🇷Seoul, Korea, Republic of
Lister Hospital
🇬🇧Hertford, United Kingdom
Centrum Medyczne Medyk - Rzeszow
🇵🇱Rzeszów, Poland
Centro Hospitalar de Lisboa Ocidental EPE - Hospital Santa Cruz
🇵🇹Carnaxide, Portugal
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario 12 De Octubre
🇪🇸Madrid, Spain
Centro Hospitalar do Medio Tejo (CHMT), E.P.E.
🇵🇹Torres Novas, Portugal
Fundacion Puigvert
🇪🇸Barcelona, Spain
Hospital de Sagunto
🇪🇸Sagunto, Spain
H U Dr. Peset
🇪🇸Valencia, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
National Taiwan University Hospital Hsin-Chu Branch
🇨🇳Hsinchu, Taiwan
North Bristol HNS Trust, Clinical Research Centre
🇬🇧Bristol, United Kingdom
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Medical University
🇨🇳New Taipei City, Taiwan
Leicester General Hospital
🇬🇧Leicester, United Kingdom
King's College Hospital
🇬🇧London, United Kingdom
Guys Hospital
🇬🇧London, United Kingdom
Salford Royal
🇬🇧Salford, United Kingdom
Royal London Hospital
🇬🇧London, United Kingdom
Stanford University
🇺🇸Stanford, California, United States
The University of Hong Kong
🇭🇰Hong Kong, Hong Kong
Changhua Christian Medical Foundation
🇨🇳Changhua, Taiwan
Christian Medical College
🇮🇳Vellore, Tamil Nadu, India
Pelican Point Dialysis - DaVita Clinical Research
🇺🇸Las Vegas, Nevada, United States
Yan Chai Hospital
🇭🇰Hong Kong, Hong Kong
Dokkyo Medical University - Saitama Medical Center
🇯🇵Saitama, Japan
Sunshine Hospital
🇦🇺Saint Albans, Victoria, Australia
CEMIC
🇦🇷Buenos Aires, Argentina
Clinica de Nefrologia Urologia y Enf. Cardiovasculares
🇦🇷Santa Fe, Argentina
Juntendo University Hospital, Tokyo
🇯🇵Tokyo, Japan
Miedzyleski Szpital Specjalistyczny
🇵🇱Warszawa, Poland
Far Eastern Memorial Hospital
🇨🇳New Taipei City, Taiwan
Osaka General Medical Center
🇯🇵Osaka, Japan
Samodzielny Publiczny ZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego
🇵🇱Łódź, Poland
Hospital Alma Mater de Antioquia
🇨🇴Medellín, Antioquia, Colombia
IPS Medicos Internistas de Caldas S.A.S
🇨🇴Manizales, Caldas, Colombia
University of Florida
🇺🇸Gainesville, Florida, United States
Peking University First Hospital
🇨🇳Beijing, China