The AFFINITY Study (Amendment 1)
Research type
Research Study
Full title
A Phase 2, Open-Label, Basket Study of Atrasentan in Patients with Proteinuric Glomerular Diseases
IRAS ID
294459
Contact name
Stephanie Turner
Contact email
Sponsor organisation
Chinook Therapeutics U.S., Inc.
Eudract number
2020-004176-18
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 3 months, 27 days
Research summary
The AFFINITY study is studying atrasentan to find
out if atrasentan delays worsening of kidney
function in patients with proteinuric kidney
disease. The mechanism of action of atrasentan
in blocking ETA receptors targets a key
pathogenic pathway common to the progression
of proteinuric glomerular disease of different
underlying etiologies. Therefore, atrasentan has
potential to be beneficial in other glomerular
diseases where proteinuria is present, such as
IgA Nephropathy, focal segmental
glomerulosclerosis (FSGS), Alport syndrome,
and diabetic kidney disease (DKD).
There is evidence supporting the evaluation of
ETA antagonists in IgAN, FSGS, Alport
syndrome, and DKD patients who are also taking
an SGLT2 inhibitor. ETA antagonism showed
reduced proteinuria in IgAN patients on an
optimized dose of a RAS inhibitor and in FSGS
patients with nephrotic syndrome. Alport
syndrome mice treated with an ETA antagonist
showed delayed onset of proteinuria and
normalized pathologic kidney and inner ear
findings on histology. In SONAR (a large Phase
3 study of atrasentan in DKD patients) there was
a small number of patients treated with
atrasentan who were also taking an SGLT2
inhibitor versus atrasentan alone who showed
greater proteinuria lowering with less fluid
retention compared to those taking atrasentan
alone.
This Phase 2, open-label basket study will
evaluate the efficacy and safety of 0.75 mg oral
atrasentan once daily in subjects with IgAN with
urine protein to creatinine ratio (UPCR) of 0.5 to
<1.0 g/g, FSGS, Alport syndrome, and diabetic
kidney disease (on top of background care of
SGLT2 inhibitor) at risk of progressive loss of
kidney function. The goal of the study is to gather
preliminary data to support moving into larger
phase 3 studies in these diseases.REC name
North East - Tyne & Wear South Research Ethics Committee
REC reference
21/NE/0053
Date of REC Opinion
25 Mar 2021
REC opinion
Further Information Favourable Opinion