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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Immunoglobulin A Nephropathy; IgA Nephropathy
• Intervention / Treatment: Drug: Placebo; Drug: Atrasentan

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.

• Study Type: Interventional
• Enrollment (Estimated): 380
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chinook Therapeutics; Phone Number: (206) 485-7051; Email: clinicaltrials@chinooktx.com

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Cemic
  • Buenos Aires, Argentina
    • Hospital Britanico de Buenos Aires
  • Mar Del Plata, Argentina
    • Centro de Investigaciones Medicas Mar Del Plata
  • Santa Fe, Argentina
    • Clinica de Nefrologia Urologia y Enf. Cardiovasculares
  • San Luis
    • Ciudad De San Luis, San Luis, Argentina, D5700CGR
      • Centro Médico Ce.Re.Ca
• Australia
  • Box Hill, Australia
    • Box Hill Hospital
  • Brisbane, Australia
    • Royal Brisbane & Women's Hospital
  • Clayton, Australia
    • Monash Medical Centre
  • Gosford, Australia
    • Renal Research
  • Kingswood, Australia
    • Nepean Hospital
  • New South Wales
    • St. Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Victoria
    • Reservoir, Victoria, Australia, 3073
      • Melbourne Renal Research Group
    • Saint Albans, Victoria, Australia, 3021
      • Sunshine Hospital
• Brazil
  • Belo Horizonte, Brazil
    • Hospital das Clínicas Universidade Federal de Minas Gerais - UFMG
  • Brasília, Brazil
    • Centro de Pesquisa Clinica do Brasil
  • Porto Alegre, Brazil
    • Santa Casa de Misericordia de Porto Alegre
  • Rio Preto, Brazil
    • Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto
  • Santo André, Brazil
    • Praxis pesquisa médica
  • São Paulo, Brazil
    • Hospital Das Clinicas Da Faculdade De Medicina Da USP
  • São Paulo, Brazil
    • Hospital do Rim Fundacao Oswaldo Ramos
  • Paraná
    • Curitiba, Paraná, Brazil
      • Instituto Pró-Renal Brasil
• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • University of Alberta Hospital
  • Ontario
    • Brampton, Ontario, Canada
      • William Osler Health System- Brampton Civic Hospital
    • London, Ontario, Canada
      • London Health Sciences Centre
    • Oshawa, Ontario, Canada
      • Lakeridge Health
    • Toronto, Ontario, Canada
      • Stephen S. Chow Medicine Professionals
    • Toronto, Ontario, Canada
      • Sunnybrook Health Institute
  • Quebec
    • Montréal, Quebec, Canada
      • Montreal General Hospital
• China
  • Beijing, China, 100044
    • Peking University People's Hospital
  • Beijing, China, 100034
    • Peking University first hospital
  • Changchun, China
    • The Second Hospital of Jilin University
  • Changsha, China
    • The Third Xiangya Hospital of Central South University
  • Chengdu, China
    • West China Hospital, Sichuan University
  • Fuzhou, China
    • The First Affiliated Hospital Of Fujian Medical University
  • Guangzhou, China
    • Nanfang Hospital of Southern Medical University
  • Hefei, China, 230601
    • The Second Hospital of Anhui Medical University
  • Jinan, China
    • Shandong University - Qilu Hospital
  • Nanchang, China
    • The First Affiliated Hospital of NanChang University
  • Shenzhen, China, 518036
    • Peking University Shenzhen Hospital
  • Anhui
    • Hefei, Anhui, China, 230022
      • The First Affiliated Hospital Anhui Medical University
  • Dongguan
    • Dongguan, Dongguan, China
      • Dongguan Tungwah Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
  • Inner Mongolia Autonomou
    • Baotou, Inner Mongolia Autonomou, China, 014010
      • The First A ffliated Hospital of Baotou Medical College, Inner Mangolia University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital
    • Nantong, Jiangsu, China, 226001
      • The Affiliated Hospital of Nantong University
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • General Hospital of Ningxia Medical University
  • Shanghai
    • Shanghai, Shanghai, China
      • Renji Hospital Shanghai Jiaotong University School of Medicine
  • Sichuan
    • Chengdu, Sichuan, China, 610072
      • People's Hospital of Sichuan Province
  • Xinjiang
    • Ürümqi, Xinjiang, China, 830054
      • The First Affiliated Hospital Xinjiang Medical University
• Colombia
  • Antioquia
    • Medellín, Antioquia, Colombia, 050010
      • Hospital Alma Mater de Antioquia
  • Atlantico
    • Barranquilla, Atlantico, Colombia, 080020
      • Clinica de la Costa Ltda
  • Caldas
    • Manizales, Caldas, Colombia, 170004
      • IPS Medicos Internistas de Caldas S.A.S
• Czechia
  • Nový Jičín, Czechia, 741 01
    • Nemocnice Novy Jicin a.s.
  • Praha, Czechia, 128 08
    • Vseobecna Fakultni Nemocnice V Praze
• France
  • Grenoble, France
    • CHU de Grenoble - Hôpital Albert Michallon
  • Le Puy-en-Velay, France
    • Ch Emile Roux
  • Paris, France
    • Hopital Necker
  • Paris, France
    • Hôpital Européen Georges-Pompidou
  • Saint-Priest-en-Jarez, France
    • CHU Saint Etienne - Hôpital Nord
  • Valenciennes, France
    • Centre Hospitalier Valenciennes
• Germany
  • Cloppenburg, Germany
    • St. Josefs-Hospital
  • Hannover, Germany
    • Medizinische Hochschule Hannover
  • Hoyerswerda, Germany
    • Nephrologisches Zentrum Hoyerswerda
  • Jena, Germany
    • Universitaetsklinikum Jena
  • Leipzig, Germany
    • Klinikum St. Georg gGmbH
  • Villingen-Schwenningen, Germany
    • Nephrologisches Zentrum Villingen-Schwenningen
  • Würzburg, Germany
    • Universitaetsklinikum Wuerzburg
• Hong Kong
  • Hong Kong, Hong Kong
    • The University of Hong Kong
  • Hong Kong, Hong Kong
    • Princess Margaret Hospital
  • Hong Kong, Hong Kong
    • Yan Chai Hospital
  • Shatin, Hong Kong
    • The Chinese University of Hong Kong
• India
  • Kerala
    • Kozhikode, Kerala, India, 673008
      • Government Medical College
  • Maharashtra
    • Pune, Maharashtra, India, 411004
      • Sahyadri Super Speciality Hospital
  • Tamil Nadu
    • Vellore, Tamil Nadu, India, 632004
      • Christian medical college
  • Telangana
    • Hyderabad, Telangana, India, 500012
      • Osmania General Hospital
    • Secunderabad, Telangana, India, 500003
      • Yashoda hospital
  • West Bengal
    • Kolkata, West Bengal, India, 700014
      • Nil Ratan Sircar Medical College & Hospital
• Ireland
  • Cork, Ireland, T12 DC4A
    • Cork University Hospital
• Italy
  • Genova, Italy
    • Azienda Ospedaliero Universitaria San Martino
  • Pavia, Italy
    • ICS Maugeri SpA SB
  • Ranica, Italy
    • Istituto Di Ricerche Farmacologiche Mario Negri
  • Lombardia
    • Milano, Lombardia, Italy, 20122
      • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
• Japan
  • Fukuoka, Japan
    • Kokura Memorial Hospital (Kokura Kinen Hospital)
  • Kahoku, Japan
    • Kanazawa Medical University
  • Kanazawa, Japan
    • Kanazawa University Hospital
  • Kashihara, Japan
    • Nara University
  • Kawasaki, Japan
    • St. Marianna University (SMU) School of Medicine
  • Niigata, Japan
    • Niigata University
  • Okayama, Japan
    • Okayama University Hospital
  • Osaka, Japan
    • Osaka General Medical Center
  • Saitama, Japan
    • Dokkyo Medical University - Saitama Medical Center
  • Shinagawa-ku, Japan
    • Showa University Hospital
  • Tokyo, Japan
    • Juntendo Nerima Hospital
  • Tokyo, Japan
    • Juntendo University Hospital, Tokyo
  • Toyoake, Japan
    • Fujita Health University Hospital
  • Urayasu, Japan
    • Juntendo University Urayasu Hospital
• Korea, Republic of
  • Anyang, Korea, Republic of
    • Hallym University Medical Center
  • Daejeon, Korea, Republic of
    • Chungnam National University Hospital
  • Gyeonggi-do, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Gyeonggi-do, Korea, Republic of, 10475
    • Myongji Hospital
  • Jeju, Korea, Republic of
    • Jeju National University Hospital
  • Seongnam-si, Korea, Republic of
    • CHA Bundang Medical Center, CHA University
  • Seoul, Korea, Republic of
    • Kyung Hee University Hospital at Gangdong
  • Seoul, Korea, Republic of
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of
    • Severance Hospital, Yonsei University Hospital
• New Zealand
  • Dunedin, New Zealand
    • Dunedin Public Hospital
  • Hamilton, New Zealand
    • Waikato Hospital
  • Papatoetoe, New Zealand
    • Middlemore Clinical Trials
• Poland
  • Rzeszów, Poland
    • Centrum Medyczne Medyk - Rzeszow
  • Warszawa, Poland
    • Miedzyleski Szpital Specjalistyczny
  • Łódź, Poland
    • Samodzielny Publiczny ZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego
• Portugal
  • Carnaxide, Portugal, 2790-134
    • Centro Hospitalar de Lisboa Ocidental EPE - Hospital Santa Cruz
  • Torres Novas, Portugal, 2350-399
    • Centro Hospitalar do Medio Tejo (CHMT), E.P.E.
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain
    • Fundacion Puigvert
  • Lugo, Spain
    • Hospital Da Marina
  • Madrid, Spain
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Sagunto, Spain
    • Hospital de Sagunto
  • Sevilla, Spain
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain
    • H U Dr. Peset
• Taiwan
  • Changhua, Taiwan
    • Changhua Christian Medical Foundation
  • Hsinchu, Taiwan
    • National Taiwan University Hospital Hsin-Chu Branch
  • New Taipei City, Taiwan
    • Far Eastern Memorial Hospital
  • New Taipei City, Taiwan
    • Taipei Medical University
  • Taipei, Taiwan
    • National Taiwan University Hospital
• United Kingdom
  • Bristol, United Kingdom, BS10 5NB
    • North Bristol HNS Trust, Clinical Research Centre
  • Hertford, United Kingdom
    • Lister Hospital
  • Leicester, United Kingdom, LE5 4PW
    • Leicester General Hospital
  • London, United Kingdom
    • Guys Hospital
  • London, United Kingdom
    • Royal London Hospital
  • London, United Kingdom, SE5 9R6
    • King's College Hospital
  • Salford, United Kingdom
    • Salford Royal
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
    • Huntsville, Alabama, United States, 35805
      • Nephrology Consultants, LLC
  • California
    • Alhambra, California, United States, 91754
      • Comprehensive Research Institute
    • Glendale, California, United States, 91204
      • Kidney Disease Medical Group
    • Long Beach, California, United States, 90806
      • Shreenath Clinical Services
    • Los Angeles, California, United States, 90022
      • Academic Medical Research Institute
    • Los Angeles, California, United States, 90095
      • UCLA Clinical and Translational Research Center
    • San Dimas, California, United States, 91773
      • Chino Valley Medical Center
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • Stanford, California, United States, 93405
      • Stanford University
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Georgia
    • Columbus, Georgia, United States, 31904
      • DCR Columbus - Renal Associates, LLC
    • Lawrenceville, Georgia, United States, 30046
      • GA Nephrology Associates
  • Illinois
    • Hinsdale, Illinois, United States, 60521
      • NANI Research, LLC
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • NANI Research, LLC
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville Physicians- Kidney Disease Program
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Intermed Consultants
  • Nevada
    • Las Vegas, Nevada, United States, 89129
      • Pelican Point Dialysis - DaVita Clinical Research
  • New York
    • Clifton Park, New York, United States, 12065
      • Capital District Renal Physicians
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mountain Kidney and Hypertension Associates
    • Winston-Salem, North Carolina, United States, 27103
      • Brookview Hills Research Associates, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • Cincinnati VA Medical Center
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • LeHigh Valley Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Dallas, Texas, United States, 75230
      • Liberty Research Center
    • Dallas, Texas, United States, 75246
      • Renal Disease Research Inst.
    • El Paso, Texas, United States, 79925
      • El Paso Kidney Specialists
    • Houston, Texas, United States, 77054
      • Prolato Clinical Research Center
    • Lufkin, Texas, United States, 75904
      • P&I Clinical Research, LLC
    • San Antonio, Texas, United States, 78258
      • San Antonio Kidney Disease Center Physicians Group, P.L.L.C
  • Virginia
    • Fairfax, Virginia, United States, 22033
      • Nephrology Associates of Northern Virginia
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Health Services
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • Milwaukee Nephrologists, SC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 m2 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.

Exclusion Criteria:

• Current diagnosis with another chronic kidney disease, including diabetic kidney disease.
• History of kidney transplantation or other organ transplantation.
• Use of systemic immunosuppressant medications, such as steroids, for more than 2 weeks in the past 3 months.
• Blood pressure above 150 mmHg systolic or 95 mmHg diastolic as evaluated by the Investigator.
• Known history of heart failure or a previous hospital admission for fluid overload.
• Clinically significant history of liver disease as assessed by the Investigator.
• Hemoglobin below 9 g/dL as measured by the Investigator or prior history of blood transfusion for anemia within the past 3 months.
• Malignancy within the past 5 years. Exceptions to this criteria include nonmelanoma skin cancer and curatively treated cervical carcinoma in situ.
• For women, pregnancy, breast feeding, or intent to become pregnant during the study. and at least 1 month afterward.
• For men, intent to father a child or donate sperm during the study.
• Have received any investigational agent or approved treatment for IgAN (other than a RAS inhibitor) including SGLT2i (except for subjects in the SGLT2i stable stratum) within 1 month (or 5 half-lives of the agent, whichever is longer) prior to Screening. If the investigational agent is a cytotoxic or immunosuppressive agent then this washout period is 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atrasentan; Once daily oral administration of 0.75 mg atrasentan for 132 weeks	Drug: Atrasentan; Film-coated tablet; Other Names: ABT-627; CHK-01; Atrasentan Hydrochloride
Placebo Comparator: Placebo; Once daily oral administration of placebo for 132 weeks	Drug: Placebo; Film-coated tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in eGFR	Change from baseline to end of study in eGFR.	Up to approximately 2.6 years
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/1.73m2, sustained for at least 30 days; Chronic dialysis ≥30 days; Kidney transplantation; All-cause mortality	Up to approximately 2.6 years
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/1.73m2, sustained for at least 30 days; Chronic dialysis ≥30 days; Kidney transplantation; All-cause mortality	Up to approximately 2.6 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in proteinuria (UPCR)	1. Change in proteinuria (UPCR) based on 24-hour urine collection in SGLT2i stable stratum compared to Placebo	Baseline to Week 36

Collaborators and Investigators

• Sponsor: Chinook Therapeutics U.S., Inc.
• Investigators: Study Director: Shuping Yang, MD, Chinook Therapeutics U.S., Inc.

Publications and helpful links

Helpful Links

• Study Website

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2020
• Primary Completion (Actual): September 7, 2023
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: September 12, 2020
• First Submitted That Met QC Criteria: September 28, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Actual): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Urologic Diseases; Kidney Diseases; Glomerular Disease; Glomerulonephritis; Kidney Disease, Chronic; Glomerulonephritis, IGA; Glomerulopathy; Immunoglobulin Disease
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Glomerulonephritis, IGA; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Endothelin Receptor Antagonists; Endothelin A Receptor Antagonists; Atrasentan
• Other Study ID Numbers: CHK01-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No