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Atrasentan in Patients With IgA Nephropathy (ALIGN)

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ClinicalTrials.gov Identifier: NCT04573478
Recruitment Status : Recruiting
First Posted : October 5, 2020
Last Update Posted : August 19, 2022
Sponsor:
Information provided by (Responsible Party):
Chinook Therapeutics, Inc. ( Chinook Therapeutics U.S., 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.

Condition or disease Intervention/treatment Phase
IgA Nephropathy Immunoglobulin A Nephropathy Drug: Atrasentan Drug: Placebo Phase 3

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 the study may be eligible to enroll in an extension study to receive open-label treatment with atrasentan under a separate protocol.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 380 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: Double-blind
Primary Purpose: Treatment
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
Actual Study Start Date : December 11, 2020
Estimated Primary Completion Date : December 1, 2023
Estimated Study Completion Date : December 1, 2025


Arm Intervention/treatment
Experimental: Atrasentan
Once daily oral administration of 0.75 mg atrasentan for 132 weeks
Drug: Atrasentan
Film-coated tablet
Other Names:
  • CHK-01
  • Atrasentan Hydrochloride
  • ABT-627

Placebo Comparator: Placebo
Once daily oral administration of placebo for 132 weeks
Drug: Placebo
Film-coated tablet




Primary Outcome Measures :
  1. Change in proteinuria [ Time Frame: Up to Week 24 or approximately 6 months ]
    The change in urine protein:creatinine ratio (UPCR) from baseline to Week 24. (non-SGLT2i stratum)


Secondary Outcome Measures :
  1. Change in eGFR [ Time Frame: Up to approximately 2.6 years ]
    Change from baseline to end of study in eGFR.

  2. Percent of subjects meeting the first composite endpoint [ Time Frame: 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/1.73m2, sustained for at least 30 days
    • Chronic dialysis ≥30 days
    • Kidney transplantation
    • All-cause mortality

  3. Percent of subjects meeting the second composite endpoint [ Time Frame: 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/1.73m2, sustained for at least 30 days
    • Chronic dialysis ≥30 days
    • Kidney transplantation
    • All-cause mortality


Other Outcome Measures:
  1. Change in proteinuria (UPCR) [ Time Frame: Baseline to Week 24 ]
    1. Change in proteinuria (UPCR) based on 24-hour urine collection in SGLT2i stable stratum compared to Placebo



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04573478


Contacts
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Contact: Chinook Therapeutics (206) 485-7051 clinicaltrials@chinooktx.com

Locations
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Sponsors and Collaborators
Chinook Therapeutics U.S., Inc.
Investigators
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Study Director: Charlotte Jones-Burton, MD, MS SVP, Product Development & Strategy
Additional Information:
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Responsible Party: Chinook Therapeutics U.S., Inc.
ClinicalTrials.gov Identifier: NCT04573478    
Other Study ID Numbers: CHK01-01
First Posted: October 5, 2020    Key Record Dates
Last Update Posted: August 19, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Chinook Therapeutics, Inc. ( Chinook Therapeutics U.S., Inc. ):
Kidney Diseases
Kidney Disease, Chronic
Urologic Diseases
Glomerulonephritis
Glomerular Disease
Glomerulonephritis, IGA
Glomerulopathy
Immunoglobulin Disease
Additional relevant MeSH terms:
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Kidney Diseases
Glomerulonephritis, IGA
Urologic Diseases
Glomerulonephritis
Nephritis
Autoimmune Diseases
Immune System Diseases
Atrasentan
Antineoplastic Agents
Endothelin A Receptor Antagonists
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action