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 was 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: Completed
• Conditions: Immunoglobulin A Nephropathy; IgA Nephropathy
• Intervention / Treatment: Drug: Placebo; Drug: Atrasentan; Drug: Atrasentan

Detailed Description

Patients with biopsy-proven IgAN who were 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, were randomized to either sequence Atrasentan/Placebo or sequence Placebo/Atrasentan in which they received 0.75 mg atrasentan once daily during one period (period A), complete a 12-week washout period, and then received matching placebo during the other period (period B) as determined by the randomization schema.

Subjects who were not on background SGLT2i therapy would first 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 remained 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 was to evaluate the efficacy of atrasentan vs. placebo while on background therapy with SGLT2i.

• 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
  • São Paulo
    • São Paulo, São Paulo, Brazil, 05403-000
      • Hospital das Clínicas da Faculdade de Medicina da USP
    • São Paulo, São Paulo, Brazil, 04038-002
      • Universidade Federal de Sao Paulo
• Malaysia
  • 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))
    • Kuala Lumpur, Kuala Lumpur, Malaysia, 59100
      • University Malaya Medical Centre
  • Perak
    • Ipoh, Perak, Malaysia, 30450
      • Hospital Raja Permaisuri Bainun (HRPB)
• South Korea
  • Busan
    • Busan, Busan, South Korea, 49201
      • Dong-A University Medical Center (Dong-A University Hospital)
  • Chungnam-Do
    • Cheonan, Chungnam-Do, South Korea, 31151
      • Soon Chun Hyang Central Medical Center (SCHMC) - Soon Chun Hyang University Hospital
  • Gyeonggi-do
    • Anyang-si, Gyeonggi-do, South Korea, 14068
      • Hallym University Sacred Heart Hospital
  • Seoul
    • Seoul, Seoul, South Korea, 06973
      • Chung-Ang University College
• 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)
  • Seville, 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 Atrasentan/Placebo; 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 Placebo/Atrasentan; 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
Percentage Change in Proteinuria (UPCR From a 24-Hour Urine Collection) From Baseline to Week 12	Change in proteinuria from Baseline to Week 12 across both periods between atrasentan versus placebo. Proteinuria was assessed using the urine protein to creatinine ratio (UPCR) measured from a 24-hour urine collection.	From Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in Proteinuria (UPCR From a 24-Hour Urine Collection) From Baseline to Week 24 in Treatment Period 2.	Change in proteinuria from Baseline to Week 24 in Treatment Period 2 between atrasentan versus placebo. Proteinuria was assessed using the urine protein to creatinine ratio (UPCR) measured from a 24-hour urine collection.	From Baseline to Week 24 of Treatment Period 2
Number of Subjects With TEAE and TEAESI	Number of Subjects With Treatment-Emergent Adverse Events (TEAE) and Treatment-Emergent Adverse Events of Special Interest (TEAESI). Severity assessment of AEs was based on CTCAE (Common Terminology Criteria for Adverse Events).	From first dose of study treatment until end of study, up to 60 weeks
Plasma Concentration of Atrasentan	Blood samples were 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

Publications and helpful links

General Publications

• Tunnicliffe DJ, Reid S, Craig JC, Samuels JA, Molony DA, Strippoli GF. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst Rev. 2024 Feb 1;2(2):CD003962. doi: 10.1002/14651858.CD003962.pub3.
• Heerspink HJL, Noronha IL, Gorriz JL, Lim SK, Kotwal SS, Kirsztajn GM, Barros Neto J, Ryan J, Fu MS, Kim SG, Barratt J, Brahmbhatt Y, Housler GJ, Jiao R, Dahlke M, Lodha A, Mottl AK; Atrasentan and Sodium Glucose Cotransporter-2 Inhibitor Efficacy and Safety Trial (ASSIST) Investigator Group. Efficacy and Safety of Atrasentan in Patients with IgA Nephropathy Receiving Sodium-Glucose Cotransporter 2 Inhibitors: Placebo-Controlled, Crossover Trial. J Am Soc Nephrol. 2026 Mar 29. doi: 10.1681/ASN.0000001076. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2023
• Primary Completion (Actual): June 30, 2025
• Study Completion (Actual): October 29, 2025

Study Registration Dates

• First Submitted: April 18, 2023
• First Submitted That Met QC Criteria: April 27, 2023
• First Posted (Actual): April 28, 2023

Study Record Updates

• Last Update Posted (Actual): July 20, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: June 1, 2026

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; Pathologic Processes; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Renal Insufficiency; Nephritis; Pathological Conditions, Signs and Symptoms; Urologic Diseases; Glomerulonephritis; Kidney Diseases; Renal Insufficiency, Chronic; Glomerulonephritis, IGA; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrrolidines; Dioxoles; Benzodioxoles; Atrasentan
• Other Study ID Numbers: CEXV811A12201; CHK01-03 (Other Identifier: Chinook Therapeutics Inc.); 2023-503828-13-00 (Other Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

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