Clinical trial NCT04573920: Atrasentan in Patients With Proteinuric Glomerular Diseases
Official title: A Phase 2, Open-Label, Basket Study of Atrasentan in Patients With Proteinuric Glomerular Diseases
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: IgA Nephropathy
Focal Segmental Glomerulosclerosis
Alport Syndrome
Diabetic Kidney Disease
Diabetic Nephropathy Type 2
Immunoglobulin A Nephropathy
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-10-05
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in proteinuria for IgAN, FSGS, and Alport syndrome patients receiving 0.75 mg atrasentan QD
timeFrame: Up to Week 12 or approximately 3 months
measure: Change in albuminuria for DKD patients
timeFrame: Up to Week 12 or approximately 3 months
measure: Change in proteinuria for FSGS patients at 1.5 mg dose
timeFrame: Up to Week 24 or approximately 6 months
measure: Change in proteinuria for FSGS patients at 1.5 mg dose
timeFrame: Up to Week 30 or approximately 7.5 months
Secondary outcomes:
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Kidney Disease Medical Group
state: California
city: Los Angeles
country: United States
facility: Academic Medical Research Institute
state: California
city: San Dimas
country: United States
facility: North America Research Institute
state: California
city: Stanford
country: United States
facility: Stanford U School Of Medicine
state: California
city: Denver
country: United States
facility: Colorado Kidney Care
state: Colorado
city: Shreveport
country: United States
facility: Northwest Louisiana Nephrology Research
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: Uni of Minnesota Hos and Clinics
state: Minnesota
city: Las Vegas
country: United States
facility: DaVita Clinical Research
state: Nevada
city: Asheville
country: United States
facility: Mountain Kidney And Hyper Associa
state: North Carolina
city: Winston-Salem
country: United States
facility: Brookview Hills Research Assoc
state: North Carolina
city: Dallas
country: United States
facility: Baylor Scott and White
state: Texas
city: Houston
country: United States
facility: Prolato Clinical Research Center
state: Texas
city: Wauwatosa
country: United States
facility: Milwaukee Nephrologists SC
state: Wisconsin
city: Gosford
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Herston
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Clayton
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Reservoir
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: St Albans
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: St Leonards
country: Australia
facility: Novartis Investigative Site
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Cheonan
country: Korea, Republic of
facility: Novartis Investigative Site
state: Chungcheongnam Do
city: Anyang Si
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Puerto De Sagunto
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Lugo
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Majadahonda
country: Spain
facility: Novartis Investigative Site
city: Sheffield
country: United Kingdom
facility: Novartis Investigative Site
state: South Yorkshire
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: