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

NCT ID: NCT05834738

Last Updated: 2025-04-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-20
• Study Completion Date: 2026-08-19

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).

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).

Conditions

IgA Nephropathy; Immunoglobulin A Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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)

Group Type: EXPERIMENTAL

Atrasentan

Intervention Type: DRUG

Period A (12 Weeks) - Film-coated tablet, Washout Period: 12 weeks, Period B (24 Weeks) - Placebo

Placebo

Intervention Type: DRUG

Placebo

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)

Group Type: EXPERIMENTAL

Atrasentan

Intervention Type: DRUG

Period B (12 Weeks) - Placebo, Washout Period: 12 weeks, Period A (24 Weeks) - Film-coated tablet

Placebo

Intervention Type: DRUG

Placebo

Interventions

Atrasentan

Period A (12 Weeks) - Film-coated tablet, Washout Period: 12 weeks, Period B (24 Weeks) - Placebo

Intervention Type: DRUG

Atrasentan

Period B (12 Weeks) - Placebo, Washout Period: 12 weeks, Period A (24 Weeks) - Film-coated tablet

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

CHK-01; Atrasentan Hydrochloride; ABT-627; CHK-01; Atrasentan Hydrochloride; ABT-627

Eligibility 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.

• 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.

• 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)

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

University of Alabama at Birmingham (UAB) - The Kirklin Clinic (TKC) - Nephrology Clinic

Birmingham, Alabama, United States

Fides Clinical Research

Atlanta, Georgia, United States

NANI Research

Oak Brook, Illinois, United States

Tufts Medical Center

Boston, Massachusetts, United States

University of North Carolina at Chapel Hill - Nephrology and Hypertension

Chapel Hill, North Carolina, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

The St. George Hospital

Kogarah, New South Wales, Australia

Prince of Wales Hospital

Sydney, New South Wales, Australia

Monash Health- Monash Medical Centre

Melbourne, Victoria, Australia

Sunshine Hospital

St Albans, Victoria, Australia

NUPEC Cardio

Belo Horizonte, Minas Gerais, Brazil

Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Universidade Federal de Sao Paulo

São Paulo, São Paulo, Brazil

Hospital das Clinicas da Faculdade de Medicina da USP

São Paulo, São Paulo, Brazil

Hopsital Sultanah Aminah Johor Bharu (HSAJB) - Bangunan Bakawali Heodialysis Centre

Johor Bahru, Johor Darul Takzim, Malaysia

Universiti Kebangsaan Malaysia (UKM) - Medical Centre (Pusat Perubatan) (Hospital Canselor Tuanku Muhriz (HCTM))

Cheras, Kuala Lumpur, Malaysia

Hospital Raja Permaisuri Bainun (HRPB)

Ipoh, Perak, Malaysia

University Malaya Medical Centre

Kuala Lumpur, , Malaysia

Soon Chun Hyang Central Medical Center (SCHMC) - Soon Chun Hyang University Hospital

Cheonan, Chungnam-Do, South Korea

Hallym University Sacred Heart Hospital

Anyang-si, Gyeonggi-do, South Korea

Dong-A University Medical Center (Dong-A University Hospital)

Busan, , South Korea

Chung-Ang University College

Seoul, , South Korea

Hospital Torrecardenas

Almería, , Spain

Hospital del Mar

Barcelona, , Spain

Hospital del Vall d´Hebron

Barcelona, , Spain

Hospital Ribera Polusa

Lugo, , Spain

Hospital Universitario De Getafe (HUG)

Madrid, , Spain

Hospital 12 de Octubre

Madrid, , Spain

Hospital Virgen Macarena

Seville, , Spain

Hospital Clinico Universitario

Valencia, , Spain

Countries

United States; Australia; Brazil; Malaysia; South Korea; Spain

References

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.

Reference Type: DERIVED

PMID: 38299639 (View on PubMed)

Other Identifiers

CHK01-03

Identifier Type: OTHER

Identifier Source: secondary_id

CEXV811A12201

Identifier Type: -

Identifier Source: org_study_id

NCT06841094

Identifier Type: -

Identifier Source: nct_alias