AFFINITY: Atrasentan in Patients With Proteinuric Glomerular Diseases

Sponsor

Chinook Therapeutics U.S., Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04573920

Collaborator

(none)

100

Enrollment

Locations

Arms

Anticipated Duration (Months)

2.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
IgA Nephropathy Focal Segmental Glomerulosclerosis Alport Syndrome Diabetic Kidney Disease Diabetic Nephropathy Type 2 Immunoglobulin A Nephropathy	Drug: Atrasentan	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 1, 2021

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Feb 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Atrasentan 0.75 mg Once daily oral administration of 0.75 mg atrasentan	Drug: Atrasentan Film-coated tablet Other Names: CHK-01 Atrasentan Hydrochloride ABT-627
Experimental: Atrasentan 1.5 mg Once daily oral administration 1.5 mg atrasentan (FSGS cohorts only)	Drug: Atrasentan Film-coated tablet Other Names: CHK-01 Atrasentan Hydrochloride ABT-627

Arm

Intervention/Treatment

Experimental: Atrasentan 0.75 mg

Once daily oral administration of 0.75 mg atrasentan

Drug: Atrasentan

Film-coated tablet

Other Names:

CHK-01

Atrasentan Hydrochloride

ABT-627

Experimental: Atrasentan 1.5 mg

Once daily oral administration 1.5 mg atrasentan (FSGS cohorts only)

Drug: Atrasentan

Film-coated tablet

Other Names:

CHK-01

Atrasentan Hydrochloride

ABT-627

Outcome Measures

Primary Outcome Measures

Change in proteinuria for IgAN, FSGS, and Alport syndrome patients receiving 0.75 mg atrasentan QD [Up to Week 12 or approximately 3 months]
The change in urine protein:creatinine ratio (UPCR) from baseline to Week 12
Change in albuminuria for DKD patients [Up to Week 12 or approximately 3 months]
The change in urine albumin:creatinine ratio (UACR) from baseline to Week 12
Change in proteinuria for FSGS patients at 1.5 mg dose [Up to Week 24 or approximately 6 months]
The change in urine protein:creatinine ratio (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:

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:

Biopsy-proven IgA nephropathy
UPCR between 0.5 to less than 1.0 g/g
Screening eGFR ≥ 30 mL/min/1.73 m2

For patients enrolling in FSGS Cohort:

Biopsy-proven FSGS or documented genetic mutation in a podocyte protein associated with FSGS
UPCR > 1.0 g/g
Screening eGFR ≥ 30 mL/min/1.73 m2
Subjects receiving systemic corticosteroids or other immunosuppressants must be on a stable dose for at least 12 weeks.
BMI ≤ 40 kg/m2

For patients enrolling in Alport syndrome Cohort:

Diagnosis of Alport syndrome by genetic testing
UPCR > 0.5 g/g
Screening eGFR ≥ 30 mL/min/1.73 m2

For patients enrolling in DKD Cohort:

Diagnosis of type 2 diabetes mellitus
UACR ≥ 0.5 g/g
Screening eGFR ≥ 45 mL/min/1.73 m2
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nephrology Consultants, LLC	Huntsville	Alabama	United States	35805
2	Comprehensive Research Institute	Alhambra	California	United States	91801
3	Kidney Disease Medical Group	Glendale	California	United States	91204
4	Academic Medical Research Institute	Los Angeles	California	United States	90022
5	North America Research Institute	San Dimas	California	United States	91773
6	Elixia Tampa, LLC	Temple Terrace	Florida	United States	33637
7	Georgia Nephrology Research Institute	Lawrenceville	Georgia	United States	30046
8	Northwest Louisiana Nephrology	Shreveport	Louisiana	United States	71101
9	Tufts Medical Center	Boston	Massachusetts	United States	02111
10	University of Minnesota Health Clinical Research Unit- A UMPhysicians Clinic	Minneapolis	Minnesota	United States	55455
11	DaVita Clinical Research	Las Vegas	Nevada	United States	89128
12	Mountain Kidney and Hypertension Associates	Asheville	North Carolina	United States	28801
13	Brookview Hills Research Associates, LLC	Winston-Salem	North Carolina	United States	27103
14	Renal Disease Research Institute, LLC	Dallas	Texas	United States	75246
15	El Paso Kidney Specialists	El Paso	Texas	United States	79925
16	Prolato Clinical Research Center	Houston	Texas	United States	77054
17	San Antonio Kidney Disease Center Physicians Group, P.L.L.C	San Antonio	Texas	United States	78258
18	Milwaukee Nephrologists, SC	Wauwatosa	Wisconsin	United States	53226
19	Renal Research	Gosford	New South Wales	Australia	2250
20	Royal North Shore Hospital	St. Leonards	New South Wales	Australia	2065
21	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4029
22	Monash Health- Monash Medical Centre	Clayton	Victoria	Australia	3168
23	Melbourne Renal Research Group	Reservoir	Victoria	Australia	3073
24	Sunshine Hospital	St Albans	Victoria	Australia	3021
25	IRCCS Ospedale Policlinico San Martino	Genova	Liguria	Italy	16132
26	Fondazione Salvatore Maugeri IRCCS	Pavia	Lombardy	Italy	27100
27	Instituto di Ricerche Farmacologiche Mario Negri, Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccó	Pavia	Lombardy	Italy
28	Kyung Hee University Hospital at Gangdong	Gangdong		Korea, Republic of
29	Hallym University Sacred Heart Hospital	Gyeonggi-do		Korea, Republic of	14068
30	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
31	Severance Hospital, Yonsei University	Seoul		Korea, Republic of	3722
32	Hospital Publico da Marina	Burela	Lugo	Spain
33	Hospital Universitario Puerta del Hierro Majadahonda	Majadahonda	Madrid	Spain	28222
34	Hospital de Sagunto	Sagunto	Valencia	Spain	46520
35	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
36	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28007
37	Royal Hospital London	London	England	United Kingdom