Inherited mitochondrial disease, including MELAS (mitochondrial Encephalopathy Lactic Acidosis and Stroke like episodes) and MIDD (Maternally Inherited Diabetes and Deafness)
Conditions
Interventions
Product Name: KH176
Product Code: KH176
Pharmaceutical Form: Oral liquid
Pharmaceutical form of the placebo: Oral liquid
Route of administration of the placebo: Oral use
Sponsors
Khondrion BV
Eligibility
Sex/Gender
All
Inclusion criteria
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
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 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. - To explore the effect of KH176 on functional clinical measures of mitochondrial disease in patients with an m.3243A>G mutation. - To investigate the tolerability and safety of KH176 following 28 days of oral administration to patients with an m.3243A>G mutation. - To investigate the multiple dose pharmacokinetics of KH176 following 28 days of oral administration in patients with an m.3243A>G mutation ;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
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Safety parameters, including cardiovascular - Pharmacokinetic parameters - Pharmacodynamic parameters (metabolome, oxidative platform, glutathione, FGF21, GDF12, PRDX1) - NMDAS Score - Spirometric parameters: Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 sec (FEV1), Peak Expiratory Flow (PEF), Maximal inspiratory mouth pressure (MIP), Maximal Expiratory mouth pressure (MEP) - 30-Seconds sit – stand test: Number of standings. - Handgrip dynamometry: Maximum grip strength - 6 Minutes Chewing test: VAS pain, VAS tiredness, Rate of Mastication, quality of movement - 6 Minutes Walk Test (during the gait evaluation): Distance - RAND-SF36 score - Hospital Anxiety and Depression Scale (HAD), supplemented with a Beck Depression Index (BDI) - Checklist Individual Strenght (CIS) - Test of Attentional Performance (TAP): Alertness and Mental Flexibility ;Timepoint(s) of evaluation of this end point: Safety parameters continuously and several assessements during treatment Pharmacokinetics on Day 1 and 28 Other assessments at baseline and after 28 days | — |
Countries
Netherlands
Contacts
Public ContactEdwin Spaans, CMO
Khondrion BV
Outcome results
None listed