New Phase 1 Trial of Potential Treatment for Mitochondrial Diseases, KL1333, Enrolling in UK

A second early clinical trial evaluating KL1333, an investigational treatment for genetic mitochondrial diseases, has enrolled its first participant, NeuroVive announced.

The Phase 1a/b trial (NCT03888716) of this small molecule treatment is recruiting healthy people and those with a genetic mitochondrial disease at its single site in Leeds, U.K. Contact information is available here.

This trial will continue to evaluate the safety and tolerability of KL1333 and its pharmacokinetics profile — sometimes described as what the body does to a medicine, or the time course of its absorption, bioavailability, distribution, metabolism, and excretion.

It will assess the therapy’s effects when delivered in multiple doses in both groups — patients and healthy people. A single dose arm will also be included for healthy volunteers. This single dose arm aims to further confirm the results of the previous randomized, single-ascending dose Phase 1 trial (NCT03056209) for KL1333.

In that initial trial, 60 healthy volunteers were given a single oral dose of either 25, 50, 100, 200, 400, 600, 800 mg of KL1333 and monitored for two weeks. Its main goal is to record adverse events.

Trial data, released in 2017, showed that KL1333 had a highly favorable and very clear dose-dependent pharmacokinetic profile.

“We are excited about this study which will take the KL1333 project further towards our goal of offering it to patients with severe genetic mitochondrial disease with few or no treatment options,” Erik Kinnman, NeuroVive’s CEO, said in a press release.

“This truly is an important project milestone for KL1333. During the past few months we have worked intensely with preparing for study start, including an optimization of the bioanalytical method” said Magnus Hansson, the company’s chief medical officer and vice president preclinical and clinical development.

KL1333 is a modulator of the cellular levels of NAD+, a central co-enzyme in the cell’s energy metabolism. In preclinical models, KL1333 was shown to increase mitochondrial energy output, reduce lactate accumulation, lower the formation of harmful free radicals, and have long-term benefits on energy metabolism, such as the formation of new mitochondria.

The U.S. Food and Drug Administration (FDA) designated KL1333 an orphan drug as a potential treatment of inherited mitochondrial respiratory chain diseases; this action gives its developer several incentives to support and speed testing.

The investigational molecule is being developed to treat primary genetic mitochondrial disorders, including mitochondrial encephalomyopathy, lactic acidosis and stroke-like episode (MELAS), Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), Pearson syndrome, and myoclonic epilepsy with ragged red fibers (MERRF) syndrome.