Atrasentan in Patients With Proteinuric Glomerular Diseases (AFFINITY)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetic Kidney Disease; Focal Segmental Glomerulosclerosis; Immunoglobulin A Nephropathy; IgA Nephropathy; Diabetic Nephropathy Type 2; Alport Syndrome
• Intervention / Treatment: Drug: Atrasentan

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chinook Therapeutics; Phone Number: (206) 485-7051; Email: clinicaltrials@chinooktx.com

Study Locations

• Australia
  • New South Wales
    • Gosford, New South Wales, Australia, 2250
      • Renal Research
    • St. Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women'S Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health- Monash Medical Centre
    • Reservoir, Victoria, Australia, 3073
      • Melbourne Renal Research Group
    • St Albans, Victoria, Australia, 3021
      • Sunshine Hospital
• Italy
  • Lazio
    • Rome, Lazio, Italy, 00165
      • Ospedale Pediatrico Bambino Gesù
  • Lombardy
    • Pavia, Lombardy, Italy, 27100
      • Fondazione Salvatore Maugeri IRCCS
• Korea, Republic of
  • Gangdong, Korea, Republic of
    • Kyung Hee University Hospital at Gangdong
  • Gyeonggi-do, Korea, Republic of, 14068
    • Hallym University Sacred Heart Hospital
  • Seoul, Korea, Republic of, 3722
    • Severance Hospital, Yonsei University
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Chungcheongnam-do
    • Cheonan-si, Chungcheongnam-do, Korea, Republic of, 31151
      • Soonchunhyang University Hospital Cheonan
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Galicia
    • Lugo, Galicia, Spain, 27004
      • Hospital Ribera Polusa
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta del Hierro Majadahonda
  • Valencia
    • Sagunto, Valencia, Spain, 46520
      • Hospital de Sagunto
• United Kingdom
  • Sheffield, United Kingdom, S5 7AU
    • Sheffield Teaching Hospitals NHS
  • England
    • London, England, United Kingdom
      • Royal Hospital London
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • Apogee Clinical Research, LLC
  • California
    • Glendale, California, United States, 91204
      • Kidney Disease Medical Group
    • Los Angeles, California, United States, 90022
      • Academic Medical Research Institute
    • San Dimas, California, United States, 91773
      • North America Research Institute
    • Stanford, California, United States, 94305
      • Stanford University
  • Colorado
    • Denver, Colorado, United States, 80230
      • Colorado Kidney Care, P.C.
  • Florida
    • Coral Springs, Florida, United States, 33701
      • South Florida Nephrology Research
    • Temple Terrace, Florida, United States, 33637
      • Elixia Tampa, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Fides Clinical Research - North Atlanta Kidney Specialist
  • Illinois
    • Hinsdale, Illinois, United States, 60521
      • NANI Research, LLC
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Northwest Louisiana Nephrology
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Health Clinical Research Unit- A UMPhysicians Clinic
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Davita Clinical Research
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mountain Kidney and Hypertension Associates
    • Winston-Salem, North Carolina, United States, 27103
      • Brookview Hills Research Associates, LLC
  • Texas
    • Dallas, Texas, United States, 75246
      • Renal Disease Research Institute, LLC
    • El Paso, Texas, United States, 79925
      • El Paso Kidney Specialists
    • Houston, Texas, United States, 77054
      • Prolato Clinical Research Center
    • San Antonio, Texas, United States, 78258
      • San Antonio Kidney Disease Center Physicians Group, P.L.L.C

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Chinook Therapeutics U.S., Inc.
• Investigators: Principal Investigator: Yasmin Brahmbhatt, MD, Chinook Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: September 28, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Endocrine System Diseases; Urogenital Abnormalities; Congenital Abnormalities; Diabetes Complications; Diabetes Mellitus; Connective Tissue Diseases; Nephritis; Glomerulonephritis; Collagen Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Diabetic Nephropathies; Glomerulosclerosis, Focal Segmental; Glomerulonephritis, IGA; Nephritis, Hereditary; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Endothelin Receptor Antagonists; Endothelin A Receptor Antagonists; Atrasentan
• Other Study ID Numbers: CHK01-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No