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Randomized, Double-blind, Placebo-controlled, Crossover Study of Atrasentan in Subjects With IgA Nephropathy (ASSIST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05834738
Recruitment Status : Recruiting
First Posted : April 28, 2023
Last Update Posted : May 22, 2024
Sponsor:
Information provided by (Responsible Party):
Chinook Therapeutics, Inc.

Brief Summary:
The ASSIST study is a phase 2, double-blind, placebo-controlled crossover study to evaluate the safety and efficacy of atrasentan vs. placebo in subjects with IgA nephropathy (IgAN) while on background standard of care therapy and an SGLT2 inhibitor (SGLT2i).

Condition or disease Intervention/treatment Phase
IgA Nephropathy Immunoglobulin A Nephropathy Drug: Atrasentan Drug: Placebo Phase 2

Detailed Description:

Approximately 52 patients with biopsy-proven IgAN who are on a background SGLT2i and a maximally tolerated and stable dose of a renin-angiotensin system inhibitor (RASi) [such as angiotensin converting enzyme inhibitor (ACEi) or angiotensin-receptor antagonist (ARB)] as part of standard of care, will be randomized to either sequence AB or sequence BA in which they will receive 0.75 mg atrasentan once daily during one period (period A), complete a 12-week washout period, and then receive matching placebo during the other period (period B) as determined by the randomization schema.

Subjects who are not on background SGLT2i therapy must be willing to undergo a run-in period of 8 weeks with an SGLT2i with a 24-hour total urine protein of > 0.85 grams/day at screening prior to the run-in period and have 24-hour total urine protein of > 0.5 grams/day at the end of the run-in period to be eligible for randomization.

Subjects will remain on their maximally tolerated and stable dose of RASi and stable dose of SGLT2i therapies for the duration of the study following randomization.

The primary objective of the study is to evaluate the efficacy of atrasentan vs. placebo while on background therapy with SGLT2i.

Subjects will have safety and efficacy assessments for 1 year (52 weeks).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double-blind
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Crossover Study of Atrasentan in Subjects With IgA Nephropathy on Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i)
Actual Study Start Date : July 20, 2023
Estimated Primary Completion Date : October 22, 2025
Estimated Study Completion Date : August 19, 2026


Arm Intervention/treatment
Experimental: Sequence AB
Once daily oral administration of 0.75 mg atrasentan for 12 weeks (Period A) followed by once daily oral administration of placebo for 24 weeks (Period B)
Drug: Atrasentan
Period A (12 Weeks) - Film-coated tablet, Washout Period: 12 weeks, Period B (24 Weeks) - Placebo
Other Names:
  • CHK-01
  • Atrasentan Hydrochloride
  • ABT-627

Drug: Placebo
Placebo

Experimental: Sequence BA
Once daily oral administration of placebo for 12 weeks (Period B) followed by once daily oral administration of 0.75 mg atrasentan for 24 weeks (Period A)
Drug: Atrasentan
Period B (12 Weeks) - Placebo, Washout Period: 12 weeks, Period A (24 Weeks) - Film-coated tablet
Other Names:
  • CHK-01
  • Atrasentan Hydrochloride
  • ABT-627

Drug: Placebo
Placebo




Primary Outcome Measures :
  1. Change From Baseline in Proteinuria at Week 12 in Both Treatment Periods 1 and 2 [ Time Frame: Baseline and 12 weeks or approximately 3 months ]
    The change in urine protein: creatinine ratio (UPCR) from baseline to Week 12


Secondary Outcome Measures :
  1. Change From Baseline in Proteinuria at Week 24 in Treatment Periods 2 [ Time Frame: Baseline and 24 weeks or approximately 6 months ]
    The change in UPCR from baseline to Week 24

  2. Number of Subjects With Adverse Events (AEs) [ Time Frame: From informed consent until end of study, approximately 60 weeks ]
    Type, incidence, severity, seriousness, and relatedness of AEs will be collected.

  3. Plasma Concentration of Atrasentan [ Time Frame: Treatment Period 1: Pre-dose on Weeks 2, 6 and 12; Treatment Period 2: Pre-dose on Weeks 2, 6, 12 and 24 ]
    Blood samples will be collected for the measurement of plasma concentrations of atrasentan.



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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:

  • Legal adults (per local and country specifications) ≥ 18 years of age at the time of signing the informed consent form (ICF) prior to initiation of any study specific activities/procedures.
  • Biopsy-proven IgA nephropathy.
  • Receiving a maximally tolerated and stable dose of a RASi for at least 12 weeks prior to screening. Investigator discretion should be used in determining maximally tolerated and optimized dose.
  • eGFR of at least 30 mL/min/1.73 m^2 at screening based on the 2021 CKD-EPI equation.
  • Willing to agree to highly effective forms of contraception, as specified in the protocol, throughout the study and for up to 1 month afterward. In WOCBP, use of hormonal contraceptive agents must have been started at least 1 month prior to baseline.
  • Willing and able to provide informed consent and comply with all study requirements.
  • Inclusion Criteria for SGLT2i stable subjects

    • Receiving a stable dose of an SGLT2i for at least 8 weeks prior to screening
    • Must have a 24-hour urine protein of >0.5 grams/day.
  • Inclusion Criteria for Run-In Subjects

    • Must have a 24-hour total urine protein of >0.85 grams/day at screening
    • Willing to participate in an 8-week run-in period with an SGLT2i (per Investigator choice)
  • Additional Inclusion Criteria for Run-in Subjects at the end of Run-In

    • Must have completed the 8-week run-in period on a stable and well tolerated dose of an SGLT2i
    • Must have a 24-hour total urine protein of >0.5 grams/day confirmed at the Run-in Week 8 visit.
    • Must have an eGFR of ≥ 30 mL/min/1.73 m^2 based on the CKD-EPI equation at their Run-in Week 8 visit.

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 prior hospital admissions for conditions relating to fluid overload that in the opinion of the Principal Investigator or Sponsor might confound the results of the study or pose additional risk to the participant by their participation in the study.
  • 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): NCT05834738


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com

Locations
Show Show 27 study locations
Sponsors and Collaborators
Chinook Therapeutics, Inc.
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Chinook Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05834738    
Other Study ID Numbers: CHK01-03
First Posted: April 28, 2023    Key Record Dates
Last Update Posted: May 22, 2024
Last Verified: May 2024

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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.:
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
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases
Glomerulonephritis
Nephritis
Autoimmune Diseases
Immune System Diseases
Atrasentan
Antineoplastic Agents
Endothelin A Receptor Antagonists
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action