A Phase II study with KH176 in patients with mitochondrial disease

Phase 1

Conditions: Inherited mitochondrial disease, including MELAS (mitochondrial Encephalopathy Lactic Acidosis and Stroke like episodes) and MIDD (Maternally Inherited Diabetes and Deafness)
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: EUCTR2016-001696-79-NL

Lead Sponsor: Khondrion BV

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

Participants in the trial will be patients with a mitochondrial DNA tRNALeu(UUR) m.3243A>G mutation and clinical signs of mitochondrial disease, including but not limited to MELAS, MIDD and mixed types.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Motoric abnormalities other than related to the mitochondrial disease interfering with the outcome parameters.
2.CPEO patients with clinical signs and symptoms restricted to the eye only
3.Heteroplasmy level as measured in urine < 20%
4.Poor nutritional state as judged by the investigator
5.Body Mass Index (BMI) not within 18.0-30.0 kg/m2 at screening.
6.History of cancer
7.Surgery or active illness of gastro-intestinal tract that might interfere with absorption.
8.Participation in a trial of an investigational product in the preceding 3 months prior to the first dose or during this trial.
9.Positive drug, alcohol or cotinine test at screening and/or admission (Day 1 of the first dosing period).
10.Clinically relevant abnormal laboratory, ECG recordings, cardiac echo (within 1 year prior to screening), vital signs or physical or mental findings at screening as judged by the Investigator.
11.Clinically relevant abnormal ECG or cardiac functioning as judged by a cardiologist.
12.ECG: QTc > 450 ms, abnormal T-wave
13.Symptomatic heart failure or signs of ischemic heart disease
14.Left Ventricular Ejaction Fraction <45%
15.History or family history of congenital Long QT syndrome
16.Increased or decreased potassium (local laboratory normal range)
17.Inadequate contraception use, pregnancy or breast feeding (females)
18.Clinically significant presence or history of allergy as judged by the Investigator.
19.History of hypersensitivity or idiosyncrasy to any of the components of the investigational drug.
20.Within 4 weeks prior to dosing, the use of (multi)vitamins, co-enzyme Q10, Vitamine E, riboflavin, and anti-oxidant supplements (and idebenone/EPI-743), as well as any medication negatively influencing mitochondrial functioning (including but not limited to valproic acid, glitazones, statins, anti-virals, amiodarone, and NSAID’s) as well as any strong Cytochrome P450 inhibitors (all ‘conazoles-anti-fungals’, HIV antivirals, grapefruit) and strong Cytochrome P450 inducers (a.o. carbamazepine, phenobarbital, phenytoin, rifampicine, St Johns wort, pioglitazone, troglitazone) as well as any medication known to affect cardiac repolarization (all anti-psychotics, several anti-depressants: nor/amytriptilline, fluoxetine, anti-emetics: domperidone (motilium) granisetron, ondansetron)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the effect of KH176 on gait (Gaitrite®) parameters: step-length and variability in step-time and step-width in patients with a m.3243A>G mutation;Secondary Objective: - To explore the effect of KH176 on biomarkers of mitochondrial functioning in patients with an m.3243A>G mutation.<br>- To explore the effect of KH176 on functional clinical measures of mitochondrial disease in patients with an m.3243A>G mutation.<br>- To investigate the tolerability and safety of KH176 following 28 days of oral administration to patients with an m.3243A>G mutation.<br>- To investigate the multiple dose pharmacokinetics of KH176 following 28 days of oral administration in patients with an m.3243A>G mutation<br>;Primary end point(s): Gait parameters: cadence, walking speed, right and left step and stride lengths, and right and left step times;Timepoint(s) of evaluation of this end point: baseline and after 28 days

Secondary Outcome Measures

Name	Time	Method

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Recruitment & Eligibility

Study & Design

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