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

Sponsor

Chinook Therapeutics, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05834738

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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: Atrasentan Drug: Placebo	Phase 2

Detailed Description

Approximately 52 patients with biopsy-proven IgAN on a background SGLT2i and a maximally tolerated and stable dose of a renin-angiotensin system (RAS) inhibitor [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.

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 Design

Study Type:

Interventional

Anticipated 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)

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2025

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in proteinuria [Up to 12 weeks or approximately 3 months]
The change in urine protein: creatinine ratio (UPCR) from baseline to Week 12

Secondary Outcome Measures

Change in proteinuria at 24 weeks of treatment [24 weeks or approximately 6 months]
The change in UPCR from baseline to Week 24

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects aged 18 and older 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 RAS inhibitor therapy (ACEi or ARB) for at least 12 weeks prior to screening. Investigator discretion should be used in determining maximally tolerated and stable dose.
eGFR of at least 30 mL/min/1.73 m2 at screening based on the 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 Week -1 Visit
Must have an eGFR of ≥ 30 mL/min/1.73 m2 based on the CKD-EPI equation at the Week -1 Visit
Receiving treatment with SGLT2i at a stable dose for at least 8 weeks prior to screening.

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 a previous hospital admission for fluid overload.
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.