Atrasentan in Patients With Proteinuric Glomerular Diseases

Diabetic Kidney Disease Clinical Trial

— AFFINITY  

Official title:

A Phase 2, Open-Label, Basket Study of Atrasentan in Patients With Proteinuric Glomerular Diseases

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04573920
• Other study ID #: CHK01-02
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 1, 2021
• Est. completion date: July 28, 2026

Study information

• Verified date: May 2024
• Source: Chinook Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The AFFINITY Study is a phase 2, open-label, basket study to evaluate the efficacy and safety of atrasentan in patients with proteinuric glomerular disease who are at risk of progressive loss of renal function.

Description:

The AFFINITY Study is a phase 2, open-label, basket study to evaluate the efficacy and safety of atrasentan in patients with proteinuric glomerular disease who are at risk of progressive loss of renal function. Cohorts will consist of patients with:

• IgA nephropathy (IgAN) with urine protein:creatinine ratio (UPCR) of 0.5 to less than 1.0 g/g

• Focal segmental glomerulosclerosis (FSGS)

• Alport syndrome

• Diabetic kidney disease (DKD) on top of background care of a RAS inhibitor and SGLT2 inhibitor

Additional cohorts may be added as data is available.

Approximately 100 patients will be enrolled in the study. Approximately 20 patients will be enrolled in each cohort to receive 0.75 mg atrasentan QD for 52 weeks. The study will also evaluate efficacy and safety of 1.5 mg atrasentan QD in FSGS subjects who received 0.75 mg atrasentan and it was well tolerated.

Patients will be allowed to continue into treatment extension and receive oral atrasentan QD for up to an additional 84 weeks (total maximum treatment of 188 weeks),

The primary objective of the study is to evaluate the effect of atrasentan on proteinuria (for IgAN, FSGS, and Alport syndrome patients) or albuminuria (for DKD patients) levels. Exploratory objectives include evaluating the change in kidney function over time as measured by eGFR, safety and tolerability. To facilitate study participation over this time period, where allowed by local regulations, options for remote study visits using telemedicine and home health may be offered.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 103
• Est. completion date: July 28, 2026
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age 18 years and older for patients in the IgAN, FSGS, and Alport Syndrome cohorts

• Age 18-70 years for patients in the DKD cohort

• Receiving a maximally tolerated dose of RAS inhibitor therapy (ACEi or ARB) that has been stable for at least 12 weeks.

• For patients enrolling in IgAN Cohort:

1. Biopsy-proven IgA nephropathy

2. UPCR between 0.5 to less than 1.0 g/g

3. Screening eGFR = 30 mL/min/1.73 m2

• For patients enrolling in FSGS Cohort:

1. Biopsy-proven FSGS or documented genetic mutation in a podocyte protein associated with FSGS

2. UPCR > 1.0 g/g

3. Screening eGFR = 30 mL/min/1.73 m2

4. Subjects receiving systemic corticosteroids or other immunosuppressants must be on a stable dose for at least 12 weeks.

5. BMI = 40 kg/m2

• For patients enrolling in Alport syndrome Cohort:

1. Diagnosis of Alport syndrome by genetic testing

2. UPCR > 0.5 g/g

3. Screening eGFR = 30 mL/min/1.73 m2

• For patients enrolling in DKD Cohort:

1. Diagnosis of type 2 diabetes mellitus

2. UACR = 0.5 g/g

3. Screening eGFR = 45 mL/min/1.73 m2

4. Receiving a stable dose of SGLT2 inhibitor for at least 12 weeks

• Willing and able to provide informed consent and comply with all study requirements

Exclusion Criteria:

• Current diagnosis of another cause of chronic kidney disease or another primary glomerulopathy.

• History of kidney transplantation or other organ transplantation.

• Except for FSGS patients, 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.

• 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 blood transfusion for anemia within the past 3 months.

• Clinical diagnosis of nephrotic syndrome

• Malignancy within the past 5 years. Exception to the criteria include nonmelanoma skin cancer and curatively treated cervical carcinoma in situ.

• For women, pregnant, breastfeeding, or intent to become pregnant during the study.

• For men, intent to father a child or donate sperm during the study.

• Recently received an investigational agent.

• Clinically significant unstable or uncontrolled medical condition as assessed by the Investigator.

Related Conditions & MeSH terms

• Alport Syndrome
• Diabetic Kidney Disease
• Diabetic Nephropathies
• Diabetic Nephropathy Type 2
• Focal Segmental Glomerulosclerosis
• Glomerulonephritis, IGA
• Glomerulosclerosis, Focal Segmental
• IgA Nephropathy
• Immunoglobulin A Nephropathy
• Kidney Diseases
• Nephritis, Hereditary

Intervention

Drug:
• Atrasentan
Film-coated tablet

Locations

Country	Name	City	State
Australia	Monash Health- Monash Medical Centre	Clayton	Victoria
Australia	Renal Research	Gosford	New South Wales
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Melbourne Renal Research Group	Reservoir	Victoria
Australia	Sunshine Hospital	St Albans	Victoria
Australia	Royal North Shore Hospital	St. Leonards	New South Wales
Italy	Fondazione Salvatore Maugeri IRCCS	Pavia	Lombardy
Italy	Ospedale Pediatrico Bambino Gesu	Rome	Lazio
Korea, Republic of	SoonChunHyang University Hospital Cheonan	Cheonan-si	Chungcheongnam-do
Korea, Republic of	Kyung Hee University Hospital at Gangdong	Gangdong
Korea, Republic of	Hallym University Sacred Heart Hospital	Gyeonggi-do
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University	Seoul
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Ribera Polusa	Lugo	Galicia
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario Puerta del Hierro Majadahonda	Majadahonda	Madrid
Spain	Hospital de Sagunto	Sagunto	Valencia
United Kingdom	Royal Hospital London	London	England
United Kingdom	Sheffield Teaching Hospitals NHS	Sheffield
United States	Mountain Kidney and Hypertension Associates	Asheville	North Carolina
United States	Fides Clinical Research - North Atlanta Kidney Specialist	Atlanta	Georgia
United States	Tufts Medical Center	Boston	Massachusetts
United States	Renal Disease Research Institute, LLC	Dallas	Texas
United States	Colorado Kidney Care, P.C.	Denver	Colorado
United States	Kidney Disease Medical Group	Glendale	California
United States	NANI Research, LLC	Hinsdale	Illinois
United States	Prolato Clinical Research Center	Houston	Texas
United States	Apogee Clinical Research, LLC	Huntsville	Alabama
United States	DaVita Clinical Research	Las Vegas	Nevada
United States	Academic Medical Research Institute	Los Angeles	California
United States	University of Minnesota Health Clinical Research Unit- A UMPhysicians Clinic	Minneapolis	Minnesota
United States	San Antonio Kidney Disease Center Physicians Group, P.L.L.C	San Antonio	Texas
United States	North America Research Institute	San Dimas	California
United States	Northwest Louisiana Nephrology	Shreveport	Louisiana
United States	Stanford University	Stanford	California
United States	Elixia Tampa, LLC	Temple Terrace	Florida
United States	Brookview Hills Research Associates, LLC	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Chinook Therapeutics U.S., Inc.

Countries where clinical trial is conducted

United States,  Australia,  Italy,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in proteinuria for IgAN, FSGS, and Alport syndrome patients receiving 0.75 mg atrasentan QD	The change in urine protein:creatinine ratio (UPCR) from baseline to Week 12	Up to Week 12 or approximately 3 months
Primary	Change in albuminuria for DKD patients	The change in urine albumin:creatinine ratio (UACR) from baseline to Week 12	Up to Week 12 or approximately 3 months
Primary	Change in proteinuria for FSGS patients at 1.5 mg dose	The change in urine protein:creatinine ratio (UPCR) from baseline to Week 24	Up to Week 24 or approximately 6 months
Primary	Change in proteinuria for FSGS patients at 1.5 mg dose	The change in urine protein:creatinine ratio (UPCR) from baseline to Week 30	Up to Week 30 or approximately 7.5 months