Date: 2017-06-27
Type of
information: Initiation of patient enrollment
phase: 2
Announcement: initiation of patient enrollment
Company: Genkyotex (Switzerland)
Product: GKT831 (formerly GKT137831)
Action
mechanism: enzyme inhibitor/NOX inhibitor. GKT-831 (formerly GKT137831) is an orally bioavailable dual inhibitor of NADPH oxidase isoforms NOX4 and NOX1. NOX enzymes exist in seven isoforms and produce reactive oxygen species (ROS). ROS can cause tissue damage and modify biological pathways that are important in a number of pathologies, including metabolic, cardiovascular, pulmonary and neurological diseases. In the kidney, NOX4 is the most abundantly expressed isoform and even further upregulated in diabetic nephropathy. The causal role of NOX enzymes in diabetic complications is well recognised. NOX4 plays a key role in glomerular damage and kidney fibrosis, which lead to albuminuria and end-stage renal disease, respectively. NOX1 is also involved in angiogenesis, atherosclerosis and other diabetic co-morbidities, making the inhibition of both the NOX1 and NOX4 enzymes by GKT137831. This competitive therapeutic profile of GKT137831 has been validated in several animal models of diabetes and diabetic nephropathy.
Disease: primary biliary cholangitis (PBC)
Therapeutic
area: Liver diseases - Hepatic diseases
Country: Canada, several undisclosed european countries, USA
Trial
details:
- The Phase 2 clinical trial is a 24-week, double-blind, placebo controlled, multi-center trial evaluating the safety and
efficacy of GKT831 in patients with PBC and inadequate response to ursodeoxycholic acid. A total of 102 PBC patients
will be enrolled in this international study and allocated to placebo or one of two doses of GKT831 (400mg once a
day or 400mg twice a day). The primary objective of the trial will be to demonstrate therapeutic activity through a
reduction of gamma glutamyl transpeptidade, a marker of liver injury, which also reflects oxidative stress. Secondary
efficacy endpoints include markers of liver inflammation and injury (CK-18, hs-CRP, ALT), non-invasive markers of
liver fibrosis (Enhanced Liver Fibrosis score, transient elastography and circulating collagen fragments).
In addition, the trial will evaluate the effect of GKT831 on bile acid metabolism, itching, autoimmunity, and quality
of life. Moreover, the trial will characterize the clinical safety profile and pharmacokinetics of GKT831 in this patient
population. An interim analysis will be performed once 90 patients have completed their week 6 visit.
Latest
news:
- • On June 27, 2017, Genkyotex announced that it has begun enrolling patients into the Phase 2 clinical trial of GKT831, its NOX1 and NOX4 enzymes inhibitor, in primary biliary cholangitis (PBC). Enrollment initiation at the first
investigational center in the U.S. took place following regulatory clearance by theFDA and local Institutional Review Board. Dosing of the first patient is expected shortly.
- Genkyotex is currently working on the activation of a large network of investigational centers participating in this
global trial. In total, over 50 centers are expected to be activated in the United States, Canada and several European
countries. Interim top-line results from the Phase 2 clinical trial are anticipated in the first half of 2018, and full
results are expected in the second half of 2018.
- • On May 2, 2017, Genkyotex announced that the FDA has accepted its Investigational New Drug (IND) Application, which allows Genkyotex to proceed with a phase 2 clinical
trial of GKT831, its NOX1 and NOX4 inhibitor, in patients with primary biliary cholangitis (PBC). Genkyotex
expects to initiate this study prior to the end of the second quarter 2017, with interim top-line results
anticipated in the first half of 2018, and full results anticipated in the second half of 2018.
Is
general: Yes
