| CTRI Number |
CTRI/2022/06/043396 [Registered on: 21/06/2022] Trial Registered Prospectively |
| Last Modified On: |
15/09/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
A study to compare the effectiveness and safety of Atrasentan to placebo in patients with IgA nephropathy (IgAN) at risk of progressive loss of renal function |
|
Scientific Title of Study
|
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) |
| Trial Acronym |
|
Secondary IDs if Any
Modification(s)
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| Secondary ID |
Identifier |
| 151085 |
Other |
| 2020-003084-26 |
EudraCT |
| CHK01-01 Amd 3.1 IN dated 12 May 2022 |
Protocol Number |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
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| Designation |
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| Affiliation |
|
| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Shweta Pradhan |
| Designation |
Head Clinical Operations |
| Affiliation |
IQVIA RDS (India) Private Limited |
| Address |
Omega Embassy Tech Square, Marathahalli - Sarjapura, Outer Ring Road, Kadubeesanahalli
Bangalore
KARNATAKA
560103
India |
| Phone |
9513774664 |
| Fax |
|
| Email |
shweta.pradhan@iqvia.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Shweta Pradhan |
| Designation |
Head Clinical Operations |
| Affiliation |
IQVIA RDS (India) Private Limited |
| Address |
Omega Embassy Tech Square, Marathahalli - Sarjapura, Outer Ring Road, Kadubeesanahalli
Bangalore
KARNATAKA
560103
India |
| Phone |
9513774664 |
| Fax |
|
| Email |
shweta.pradhan@iqvia.com |
|
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Source of Monetary or Material Support
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| Chinook Therapeutics U.S., Inc. Seattle, WA 98109 |
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Primary Sponsor
|
| Name |
Chinook Therapeutics |
| Address |
U.S., Inc. Seattle, WA 98109 |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
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Details of Secondary Sponsor
|
| Name |
Address |
| IQVIA RDS India Private Limited |
Omega Embassy Tech Square Marathahalli Sarjapur Outer Ring Road Kadubeesanahalli Bangalore KA 560103. |
|
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Countries of Recruitment
|
Argentina
Australia
Brazil
Canada
China
Colombia
Czech Republic
France
Germany
Hong Kong
India
Ireland
Italy
Japan
New Zealand
Poland
Portugal
Republic of Korea
Spain
Taiwan
United Kingdom
United States of America |
Sites of Study
Modification(s)
|
| No of Sites = 6 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Suceena Alexander |
Christian Medical College |
Nephrology Department,
1st floor A Block, Christian Medical College Ranipet Campus,
Kilminnal Village, Ranipet - 632517, Tamil Nadu, India
Vellore
TAMIL NADU |
9662490598
suceena@gmail.com |
| Dr Binoj Panekkatil |
Government Medical College Kozhikode |
Department of Nephrology Government Medical College Campus, Medical College Junction, 17, Mavoor Road, Near Police Station
Kozhikode
KERALA |
9809955936
Dr.binojnephrocmc@gmail.com |
| Dr Pinaki Mukhop adhyay |
Nil Ratan Sircar Medical College & Hospital |
138 AJC Bose Road Kolkata 700014
Kolkata
WEST BENGAL |
9231978078
drpinaki@yahoo.com |
| Dr Manisha Sahay |
Osmania General Hospital |
Department of Nephrology Afzalgunj Hyderabad 500012
Hyderabad
TELANGANA |
9849097507
drmanishasahay@gmail.com |
| Dr Atul Dattatraya Sajgure |
Sahyadri Super Specialty Hospital |
30 C Erandwane Karve Road Pune 411004
Pune
MAHARASHTRA |
9890676278
atulsajgure@yahoo.com |
| Dr V Suresh Babu |
Yashoda Hospital |
behind Hari Hara Kalabhavan S P road Secunderabad – 500003
Hyderabad
TELANGANA |
9849304805
sukonda2007@gmail.com |
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Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 6 |
| Name of Committee |
Approval Status |
| Ethics Committee, N.R.S Medical College |
Approved |
| Institutional Ethics Committee, Govt Medical College |
Approved |
| Institutional Ethics Committee, Osmania Medical College Koti |
Approved |
| Institutional Review Board Christian Medical College |
Approved |
| Sahyadri Hospitals Limited Ethics Committee |
Approved |
| Yashoda Academy of Medical Education & Research IEC |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
, (1) ICD-10 Condition: N178||Other acute kidney failure, |
|
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Atrasentan (Active) |
0.75 mg per tablet, 1 tablet QD, Oral Route for 132 weeks
|
| Comparator Agent |
Placebo |
Matching placebo film-coated round tablets, 1 tablet QD for 132 weeks |
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Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
Age and Sex
Male and female subjects aged 18 and older at the time of signing the ICF prior to initiation of any study specific activities/procedures.
Types of Subjects and Disease Characteristics
Biopsy-proven IgAN that, in the opinion of the Investigator, is not due to secondary causes.
Biopsy could have occurred at any point in time prior to study.
A diagnostic report must be available for review by the Sponsor or designee.
Receiving a maximally tolerated and optimized dose of a RAS inhibitor that has been stable for at least 12 weeks prior to screening.
Investigator discretion should be used in determining maximally tolerated and optimized dose.
Subjects who are intolerant to RAS inhibitors are eligible but will not exceed Approximately 5 percent of total population randomized.
Total urine protein greater than or equal to 1g/day as measured via 24-hour urine collection at a central laboratory collected at Screening
eGFR of at least 30 mL per min per 1.73 mL at screening based on the CKD EPI equation.
Pregnancy and Contraception
All fertile men and WOCBP 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 hormonal contraceptive agents must have been started at least 1 month prior to baseline.
Informed Consent
Willing and able to provide written informed consent and comply with all study visits and study procedures.
|
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| ExclusionCriteria |
| Details |
Subjects must meet NONE of the following exclusion criteria to be enrolled.
Concurrent diagnosis of another cause of chronic kidney disease including diabetic kidney disease or another primary glomerulopathy.
Clinical suspicion of rapidly progressive glomerulonephritis (RPGN) based on KDIGO guidelines or clinical suspicion of Henoch-Schonlein Purpura.
Clinical diagnosis of nephrotic syndrome
BNP value of more than 200 mg per mL at screening.
Platelet count less than 80,000 per µL at screening.
History of organ transplantation (subjects with history of corneal transplant are not excluded).
Use of systemic immunosuppressant medications including including systemic corticosteroids
(e.g., prednisone, prednisolone, etc.), mycophenolate, azathioprine, cyclosporine, tacrolimus, etc.; use of herbs such as Tripterygium Wilfordii Hook F, Caulis sinomenii and Sinomenium acutum; for more than 2 weeks in the past 3 months. Use of rituximab within the past 6 months.
Confirmed blood pressure more than 150 mmHg systolic or more than 95 mmHg diastolic based on a mean of 3 measurements obtained at screening.
Known history of heart failure or prior hospital admissions for conditions relating to fluid overload such as pulmonary edema, uncontrolled peripheral edema, pleural effusion, or ascites.
Known history of clinically significant liver disease or transaminase or bilirubin values more than twice the upper limit of normal. Subjects with treated hepatitis C can be considered for inclusion into the study upon consultation with the Sponsor’s Medical Monitor (or designee).
Hemoglobin below 9 g per dL at screening or prior history of blood transfusion for anemia within 3 months of screening.
History of malignancy unless cancer free for at least 5 years or nonmelanoma skin cancer not requiring ongoing treatment. A subject with curatively treated cervical carcinoma in situ is eligible for this study.
Pregnancy, breast feeding, or intent to become pregnant during the study period and at least 1 month afterward for females.
Intent to father a child or donate sperm during the study period and at least 1 month afterward for males.
Have received any investigational agent or approved treatment for IgAN (other than a
RAS inhibitor) including SGLT2 inhibitors 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.
Concurrent clinically significant, unstable, or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the Investigator or Sponsor’s Medical Monitor (or designee), might confound the results of the study or pose additional risk to the subject by their participation in the study.
History of an alcohol or illicit drug-related disorder within the past 3 years.
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Method of Generating Random Sequence
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Computer generated randomization |
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Method of Concealment
|
Centralized |
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Blinding/Masking
|
Double Blind Double Dummy |
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Primary Outcome
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| Outcome |
TimePoints |
| To evaluate the effect of atrasentan versus placebo on proteinuria levels at Week 24 |
The change in proteinuria (urine protein: creatinine ratio [UPCR] based on 24-hour urine collection) from baseline to Week 24 |
|
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Secondary Outcome
|
| Outcome |
TimePoints |
| To evaluate the effect of atrasentan versus placebo on change from baseline to Week 136 (4 weeks post cessation of randomized treatment) in estimated glomerular filtration rate (eGFR) |
Change from baseline to final study visit (Week 136) in eGFR, using the chronic kidney disease-epidemiology collaboration (CKD-EPI) creatinine equation. |
| To compare 2-year on-treatment rates of change in eGFR between atrasentan and placebo (eGFR slope Week 12 to Week 120 of randomized treatment) |
Rate of change in eGFR during 2 years on treatment as measured through a chronic slope calculated from values at Week 12 through to Week 120 |
| 3. To compare the total on-study rates of change in eGFR between atrasentan and placebo (eGFR slope from baseline to Week 136). |
Rate of change in eGFR during the study as measured through a total slope calculated from values at baseline to Week 136 |
| Additional efficacy outcomes |
• Percent of subjects achieving proteinuria reduction to more than1 g per day at Week 24 and 40% decrease in UPCR from baseline.
• Percent of subjects experiencing at least a 30% reduction in eGFR or reach end-stage kidney disease (ESKD) during the study.
• Percent of subjects experiencing at least a 40% reduction in eGFR or reach ESKD during the study Safety.
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Target Sample Size
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Total Sample Size="320"
Sample Size from India="15"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
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Phase 3 |
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Date of First Enrollment (India)
|
15/07/2022 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
15/03/2021 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="5"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
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Publication Details
|
Not applicable |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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Brief Summary
|
This is a Phase 3, randomized, double-blind, placebo-controlled study to compare the efficacy and safety of atrasentan to placebo in subjects with IgAN at risk of progressive loss of renal function. All subjects participating in the study will be required to be on a maximally tolerated and stable dose of RAS inhibitor (physician choice) throughout the study. The study is comprised of an optional pre-screening period, a screening period, a treatment period and a follow-up period. After signing an ICF for the study, subjects will be screened for study eligibility over 4 weeks. UPCR eligibility will be determined from first morning void (FMV) urine sample at Screening. On Day 1, eligible subjects will be randomized 1:1 to receive atrasentan 0.75 mg QD or a matched placebo for 132 weeks. Randomization will be stratified according to region and screening UPCR levels. At Week 1, subjects will have a telephone contact for safety evaluation. Subsequently and throughout the treatment period, subjects will be evaluated for change in proteinuria and eGFR from baseline; subjects will also be monitored for adverse events (AEs), clinically significant changes in laboratory assessments, ECG findings, and vital signs including weight and blood pressure. Pregnancy testing for women of childbearing potential (WOCBP) and counselling for men and women on study contraception requirements will also occur throughout the study. Subjects will be requested to monitor their weight weekly for the first 2 weeks on study drug. Following the end of treatment, subjects will have follow-up evaluations for safety and efficacy at Week 134 and 136 (EoS). |