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

A Randomized, Double-blind, Placebo-controlled, Crossover Study of Atrasentan in Subjects With IgA Nephropathy on Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i)

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).

Study Overview

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

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).

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • The St. George Hospital
    • Sydney, New South Wales, Australia, 2031
      • Prince of Wales Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3168
      • Monash Health- Monash Medical Centre
    • St Albans, Victoria, Australia, 3021
      • Sunshine Hospital
• Brazil
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30220-140
      • NUPEC Cardio
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-074
      • Santa Casa de Misericordia de Porto Alegre
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 05403-000
      • Hospital das Clínicas da Faculdade de Medicina da USP
    • São Paulo, Sao Paulo, Brazil, 04038-002
      • Universidade Federal de Sao Paulo
• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • Dong-A University Medical Center (Dong-A University Hospital)
  • Seoul, Korea, Republic of, 06973
    • Chung-Ang University College
  • Chungnam-Do
    • Cheonan, Chungnam-Do, Korea, Republic of, 31151
      • Soon Chun Hyang Central Medical Center (SCHMC) - Soon Chun Hyang University Hospital
  • Gyeonggi-do
    • Anyang, Gyeonggi-do, Korea, Republic of, 14068
      • Hallym University Sacred Heart Hospital
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Centre
  • Johor Darul Takzim
    • Johor Bahru, Johor Darul Takzim, Malaysia, 80100
      • Hopsital Sultanah Aminah Johor Bharu (HSAJB) - Bangunan Bakawali Heodialysis Centre
  • Kuala Lumpur
    • Cheras, Kuala Lumpur, Malaysia, 56000
      • Universiti Kebangsaan Malaysia (UKM) - Medical Centre (Pusat Perubatan) (Hospital Canselor Tuanku Muhriz (HCTM))
  • Perak
    • Ipoh, Perak, Malaysia, 30450
      • Hospital Raja Permaisuri Bainun (HRPB)
• Spain
  • Almería, Spain, 04009
    • Hospital Torrecardenas
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08035
    • Hospital del Vall d´Hebron
  • Lugo, Spain, 27004
    • Hospital Ribera Polusa
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
  • Madrid, Spain, 28009
    • Hospital Universitario De Getafe (HUG)
  • Sevilla, Spain, 41009
    • Hospital Virgen Macarena
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham (UAB) - The Kirklin Clinic (TKC) - Nephrology Clinic
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Fides Clinical Research
  • Illinois
    • Oak Brook, Illinois, United States, 60523
      • NANI Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill - Nephrology and Hypertension
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • UNIVERSITY of PENNSYLVANIA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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: Placebo; Placebo; Drug: Atrasentan; Period A (12 Weeks) - Film-coated tablet, Washout Period: 12 weeks, Period B (24 Weeks) - Placebo; Other Names: ABT-627; CHK-01; Atrasentan Hydrochloride; Drug: Atrasentan; Period B (12 Weeks) - Placebo, Washout Period: 12 weeks, Period A (24 Weeks) - Film-coated tablet; Other Names: ABT-627; CHK-01; Atrasentan Hydrochloride
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: Placebo; Placebo; Drug: Atrasentan; Period A (12 Weeks) - Film-coated tablet, Washout Period: 12 weeks, Period B (24 Weeks) - Placebo; Other Names: ABT-627; CHK-01; Atrasentan Hydrochloride; Drug: Atrasentan; Period B (12 Weeks) - Placebo, Washout Period: 12 weeks, Period A (24 Weeks) - Film-coated tablet; Other Names: ABT-627; CHK-01; Atrasentan Hydrochloride

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Proteinuria at Week 24 in Treatment Periods 2	The change in UPCR from baseline to Week 24	Baseline and 24 weeks or approximately 6 months
Number of Subjects With Adverse Events (AEs)	Type, incidence, severity, seriousness, and relatedness of AEs will be collected.	From informed consent until end of study, approximately 60 weeks
Plasma Concentration of Atrasentan	Blood samples will be collected for the measurement of plasma concentrations of atrasentan.	Treatment Period 1: Pre-dose on Weeks 2, 6 and 12; Treatment Period 2: Pre-dose on Weeks 2, 6, 12 and 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2023
• Primary Completion (Estimated): October 22, 2025
• Study Completion (Estimated): August 19, 2026

Study Registration Dates

• First Submitted: February 20, 2025
• First Submitted That Met QC Criteria: February 20, 2025
• First Posted (Estimated): February 24, 2025

Study Record Updates

• Last Update Posted (Estimated): February 24, 2025
• Last Update Submitted That Met QC Criteria: February 20, 2025
• Last Verified: February 1, 2025

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: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Kidney Diseases; Glomerulonephritis, IGA; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Endothelin A Receptor Antagonists; Endothelin Receptor Antagonists; Atrasentan
• Other Study ID Numbers: CHK01-03 (Other Identifier: Chinook Therapeutics Inc.)

Drug and device information, study documents

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