Atrasentan in Patients With IgA Nephropathy

IgA Nephropathy Clinical Trial

— ALIGN  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04573478
• Other study ID #: CHK01-01
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 11, 2020
• Est. completion date: December 1, 2026

Study information

• Verified date: May 2024
• Source: Chinook Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 380
• Est. completion date: December 1, 2026
• Est. primary completion date: September 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• IgA Nephropathy
• Immunoglobulin A Nephropathy
• Kidney Diseases

Intervention

Drug:
• Atrasentan
Film-coated tablet
• Placebo
Film-coated tablet

Locations

Country	Name	City	State
Argentina	CEMIC	Buenos Aires
Argentina	Hospital Britanico de Buenos Aires	Buenos Aires
Argentina	Centro Médico Ce.Re.Ca	Ciudad De San Luis	San Luis
Argentina	Clinica de Nefrologia Urologia y Enf. Cardiovasculares	Santa Fe
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	Melbourne Renal Research Group	Reservoir	Victoria
Australia	Sunshine Hospital	Saint Albans	Victoria
Australia	Royal North Shore Hospital	St. Leonards	New South Wales
Brazil	Hospital das Clínicas Universidade Federal de Minas Gerais - UFMG	Belo Horizonte
Brazil	Centro de Pesquisa Clinica do Brasil	Brasília
Brazil	Instituto Pró-Renal Brasil	Curitiba	Paraná
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
Canada	London Health Sciences Centre	London	Ontario
Canada	Stephen S. Chow Medicine Professionals	Toronto	Ontario
China	The First A ffliated Hospital of Baotou Medical College, Inner Mangolia University of Science and Technology	Baotou	Inner Mongolia Autonomou
China	Peking University First Hospital	Beijing
China	Peking University People's Hospital	Beijing
China	The Second Hospital of Jilin University	Changchun
China	The Third Xiangya Hospital of Central South University	Changsha
China	People's Hospital of Sichuan Province	Chengdu	Sichuan
China	West China Hospital, Sichuan University	Chengdu
China	Dongguan Tungwah Hospital	Dongguan	Dongguan
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
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
China	Shandong University - Qilu Hospital	Jinan
China	The First Affiliated Hospital of Nanchang University	Nanchang
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	The Affiliated Hospital of Nantong University	Nantong	Jiangsu
China	Renji Hospital Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Peking University Shenzhen Hospital	Shenzhen
China	The First Affiliated Hospital Xinjiang Medical University	Ürümqi	Xinjiang
Colombia	IPS Medicos Internistas de Caldas S.A.S	Manizales	Caldas
Colombia	Hospital Alma Mater de Antioquia	Medellín	Antioquia
France	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
Germany	St. Josefs-Hospital	Cloppenburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Nephrologisches Zentrum Hoyerswerda	Hoyerswerda
Germany	Universitaetsklinikum Jena	Jena
Germany	Nephrologisches Zentrum Villingen-Schwenningen	Villingen-Schwenningen
Germany	Universitaetsklinikum Wuerzburg	Würzburg
Hong Kong	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
India	Osmania General Hospital	Hyderabad	Telangana
India	Nil Ratan Sircar Medical College & Hospital	Kolkata	West Bengal
India	Government Medical College	Kozhikode	Kerala
India	Sahyadri Super Speciality Hospital	Pune	Maharashtra
India	Yashoda Hospital	Secunderabad	Telangana
India	Christian Medical College	Vellore	Tamil Nadu
Italy	Azienda Ospedaliero Universitaria San Martino	Genova
Italy	Fondazione IRCCS CA Granda Ospedale Maggiore Policlinico	Milano	Lombardia
Italy	Seconda Università degli Studi di Napoli	Naples
Italy	ICS Maugeri SpA SB	Pavia
Japan	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
Korea, Republic of	Hallym University Medical Center	Anyang
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Myongji Hospital	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-do
Korea, Republic of	Jeju National University Hospital	Jeju
Korea, Republic of	CHA Bundang Medical Center, CHA University	Seongnam-si
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Kyung Hee University Hospital at Gangdong	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Hospital	Seoul
New Zealand	Waikato Hospital	Hamilton
New Zealand	Middlemore Clinical Trials	Papatoetoe
Poland	Samodzielny Publiczny ZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego	Lódz
Poland	Centrum Medyczne Medyk - Rzeszow	Rzeszów
Poland	Miedzyleski Szpital Specjalistyczny	Warszawa
Portugal	Centro Hospitalar de Lisboa Ocidental EPE - Hospital Santa Cruz	Carnaxide
Portugal	Centro Hospitalar do Medio Tejo (CHMT), E.P.E.	Torres Novas
Spain	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	Sevilla
Spain	H U Dr. Peset	Valencia
Taiwan	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
United Kingdom	North Bristol HNS Trust, Clinical Research Centre	Bristol
United Kingdom	Lister Hospital	Hertford
United Kingdom	Leicester General Hospital	Leicester
United Kingdom	Guys Hospital	London
United Kingdom	King's College Hospital	London
United Kingdom	Royal London Hospital	London
United Kingdom	Salford Royal	Salford
United States	Comprehensive Research Institute	Alhambra	California
United States	Mountain Kidney and Hypertension Associates	Asheville	North Carolina
United States	Lehigh Valley Hospital	Bethlehem	Pennsylvania
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Tufts Medical Center	Boston	Massachusetts
United States	Capital District Renal Physicians	Clifton Park	New York
United States	Liberty Research Center	Dallas	Texas
United States	El Paso Kidney Specialists	El Paso	Texas
United States	Nephrology Associates Of Northern Virginia	Fairfax	Virginia
United States	NANI Research, LLC	Fort Wayne	Indiana
United States	University of Florida	Gainesville	Florida
United States	Kidney Disease Medical Group	Glendale	California
United States	NANI Research, LLC	Hinsdale	Illinois
United States	Pelican Point Dialysis - DaVita Clinical Research	Las Vegas	Nevada
United States	GA Nephrology Associates	Lawrenceville	Georgia
United States	University of Louisville Physicians- Kidney Disease Program	Louisville	Kentucky
United States	Intermed Consultants	Minneapolis	Minnesota
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Swedish Health Services	Seattle	Washington
United States	Stanford University	Stanford	California
United States	Brookview Hills Research Associates, LLC	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Chinook Therapeutics U.S., Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  China,  Colombia,  France,  Germany,  Hong Kong,  India,  Italy,  Japan,  Korea, Republic of,  New Zealand,  Poland,  Portugal,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Double-blind period: Change in eGFR	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)	Up to Week 136, 4 weeks post end of treatment
Secondary	Double-blind period: Percent of subjects meeting the first composite endpoint	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 mortality	Up to approximately 2.6 years
Secondary	Double-blind period: Percent of subjects meeting the second composite endpoint	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 mortality	Up to approximately 2.6 years
Secondary	Double-blind period: Percent of subjects achieving reduction of proteinuria to < 1 g/day at 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).	Baseline to Week 36
Secondary	Double-blind period: Number of Subjects With TEAEs	Type, incidence, severity, seriousness, and relatedness of TEAEs.	From first dose of study drug up to 4 weeks post end of treatment in double-blind period, 136 weeks
Secondary	Double-blind period: Number of Subjects With AESI Including Events of Fluid Overload	Incidence, severity, seriousness, and relatedness AESIs.	From first dose of study drug up to 4 weeks post end of treatment in double-blind period, 136 weeks
Secondary	Open-label period: Change in proteinuria	Change in UPCR based on 24-hour urine collection.	Open-label Baseline to open-label Week 36
Secondary	Open-label period: Change in eGFR	Change from open-label Baseline to open-label Week 52 using the CKD-EPI creatinine equation.	Open-label Baseline to open-label Week 52