The KHENERGYC Study

Inclusion Criteria: 1. Age between 0 months and 17 years 2. Genetically confirmed mitochondrial disease, of which the gene defect is known to decrease one or more oxidative phosphorylation system enzymes and who suffer from motor symptoms, based on investigator judgement 3. Abnormal gross motor function and/or presence of at least one clinically significant motor symptom (hypotonia, decreased muscle strength, ataxia, dystonia, chorea and/or spasticity) based on investigator judgement 4. Before enrollment in the adaptive PK phase and before randomization into the double-blind placebo-controlled phase: Gross Motor Function Measure-88 (GMFM-88) Total Score ≤96% 5. Before enrollment in the adaptive PK phase and before randomization into the double-blind placebo-controlled phase: International Paediatric Mitochondrial Disease Scale IPMDS Score ≥10 6. Stable disease symptoms since the previous routine control visit (consistent with a score of "stable" on the item "disease course since previous IPMDS" of the IPMDS) in the opinion of the investigator. 7. Written informed (patient/parental/caregiver) consent, able and willing to comply with the study requirements of the study protocol. 8. Women of childbearing potential must be willing to use highly effective contraceptive methods during the entire study, i.e. combined (estrogen and progestogen containing) oral, intravaginal or transdermal hormonal contraception associated with inhibition of ovulation; oral, injectable, or or implantable progestogen-only hormonal contraception associated with inhibition of ovulation; use of an intrauterine device; an intrauterine hormone releasing system, bilateral tubal occlusion and vasectomy of the partner. Any hormonal contraception method must be supplemented with a barrier method (preferably male condom). Vasectomised partner is considered a highly effective birth control method provided that partner is the sole sexual partner of the subject and that the vasectomised partner has received medical assessment of the surgical success. Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. Reliability of sexual abstinence needs to be evaluated in in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Note 1: Natural family planning methods, female condom, cervical cap or diaphragm are not considered adequate contraceptive methods in the context of this study. Note 2: To be considered not of childbearing potential, potential female subjects must have been surgically sterilized (bilateral tubal ligation, hysterectomy or bilateral oophorectomy) for at least 6 months prior to Screening. Note 3: KH176 has been shown non-genotoxic judged from the Ames test, Chromosomal Aberration test and in vivo Micronucleus test. Moreover, appreciable systemic exposure from the exposure to (\~2.5 mL) semen is extremely unlikely. However, until reproductive toxicology studies have confirmed that KH176 does not adversely affect normal reproduction in adult males and females, as well as causing developmental toxicity in the offspring, the following contraceptive precautions must be adhered to: * male subjects with female partners of childbearing potential must be willing to use condoms during the entire study. * female partners of childbearing potential of male subjects must be willing to use adequate contraceptive methods during the entire study, i.e., a hormonal contraceptive method (pill, vaginal ring, patch, implant, injectable, hormone-medicated intrauterine device) or an intrauterine device. Exclusion criteria: 1. Surgery of the gastro-intestinal tract with removal of piece(s) of stomach, duodenum or jejunum that might interfere with absorption. Feeding through gastrostomy tube is however allowed. 2. Treatment with an investigational product within 3 months or 5 times the half-life of the investigational product (whichever is longer) prior to the first dose of the study medication. 3. Clinically relevant cardiovascular disease or risk factors for arrythmia: 1. Abnormal ECG (including QTcF exceeding the 95th percentile for the age- and sex-dependent QTc interval (https://www.qtcalculator.org) and/or abnormal structural or functional 2D ECHO 2. Systolic Blood Pressure (SBP) above the 95th percentile for the sex, age group and height percentile at screening or baseline on single measurement (see appendix 1) 3. History of acute or chronic heart failure, (family) history of unexplained syncope or congenital long and short QT syndrome or sudden death 4. Hyperkalemia or hypokalemia; hypomagnesemia or hypermagnesemia; hypocalcemia or hypercalcemia (local laboratory normal values; to be judged by investigator) 4. Clinically relevant abnormal laboratory results: 1. Aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) \> 3 times upper limit of normal (ULN), or bilirubin \> 3 x ULN. If a patient has ASAT or ALAT \> 3 x ULN but \< 3.5 x ULN, re-assessment is allowed at the investigator's discretion. 2. Estimated glomerular filtration rate below age-appropriate limits (according to the formula: 40.9\* ((1.8 / Cystatine C)0.93): \< 2 months: \< 25 ml/min/1.73 m2 2 months to 1 year: \< 35 ml/min/1.73 m2 \> 1 year: \< 60 ml/min/1.73 m2 3. All other clinically relevant parameters at screening or baseline as judged by the investigator 5. History of hypersensitivity or idiosyncrasy to any of the components of the investigational product. 6. Medical history of drug abuse (illegal drugs such as cannabinoids, amphetamines, cocaine, opiates or problematic use of prescription drugs such as benzodiazepines, opiates). 7. The use of any of the following medication and/or supplements within 4 weeks or 5 times the half-life (whichever is longer) prior to the first dosing of the study medication: 1. (multi)vitamins, co-enzyme Q10, Vitamin E, riboflavin, and antioxidant supplements (including, but not limited to idebenone/EPI-743, mitoQ); unless stable for at least one month before first dosing and remaining stable throughout the study. 2. any medication negatively influencing mitochondrial functioning (including but not limited to valproic acid, glitazones, statins, anti-virals, amiodarone, and non-steroidal anti- inflammatory drugs (NSAIDs)), unless stable for at least one month before first dosing and remaining stable throughout the study. Note: thus, mitoQ and any medication negatively influencing mitochondrial functioning are allowed as long as the dose has been stable for at least one month prior to first dosing and remains stable throughout the study. 3. any strong Cytochrome P450 (CYP)3A4 inhibitors (all 'conazoles-anti-fungals', HIV antivirals, grapefruit). 4. strong CYP3A4 inducers (including HIV antivirals, carbamazepine, phenobarbital, phenytoin, rifampicin, St. John's wort, pioglitazone, troglitazone). 5. any medication known to affect cardiac repolarisation, unless the QTc interval at screening is normal during stable treatment for a period of two weeks, or 5 half-lives of the medication and its major metabolite(s), whichever period is the shortest (all anti-psychotics, several anti-depressants: nor- / amitriptyline, fluoxetine, anti-emetics: domperidone (Motilium®), granisetron, ondansetron). 6. any medication metabolised by CYP3A4 with a narrow therapeutic width.