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

IgA Nephropathy Clinical Trial

— ASSIST  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05834738
• Other study ID #: CHK01-03
• Status: Recruiting
• Phase: Phase 2
• Start date: July 20, 2023
• Est. completion date: August 19, 2026

Study information

• Verified date: May 2024
• Source: Chinook Therapeutics, Inc.
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 52
• Est. completion date: August 19, 2026
• Est. primary completion date: October 22, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• IgA Nephropathy
• Immunoglobulin A Nephropathy
• Kidney Diseases

Intervention

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

Locations

Country	Name	City	State
Australia	Monash Health- Monash Medical Centre	Clayton	Victoria
Australia	The St. George Hospital	Kogarah	New South Wales
Australia	Sunshine Hospital	St Albans	Victoria
Australia	Prince of Wales Hospital	Sydney	New South Wales
Brazil	NUPEC Cardio	Belo Horizonte	Minas Gerais
Brazil	Santa Casa de Misericordia de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital das Clinicas da Faculdade de Medicina da USP	São Paulo	Sao Paulo
Brazil	Universidade Federal de Sao Paulo	São Paulo	Sao Paulo
Korea, Republic of	Hallym University Sacred Heart Hospital	Anyang	Gyeonggi-do
Korea, Republic of	Dong-A University Medical Center (Dong-A University Hospital)	Busan
Korea, Republic of	Soon Chun Hyang Central Medical Center (SCHMC) - Soon Chun Hyang University Hospital	Cheonan	Chungnam-Do
Korea, Republic of	Chung-Ang University College	Seoul
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
Spain	Hospital Torrecardenas	Almería
Spain	Hospital del Vall d´Hebron	Barcelona
Spain	Hospital Clinico Universitario	Ibáñez	Valencia
Spain	Hospital Ribera Polusa	Lugo	Galicia
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Universitario De Getafe (HUG)	Madrid
Spain	Hospital del Mar	Passeig Marítim	Barcelona
Spain	Hospital Virgen Macarena	Sevilla
United States	University of Alabama at Birmingham (UAB) - The Kirklin Clinic (TKC) - Nephrology Clinic	Birmingham	Alabama
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	NANI Research	Oak Brook	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Chinook Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Korea, Republic of,  Malaysia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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