TABLE 1.

Ongoing^a clinical trials targeting primary mitochondrial disease

Therapy	Clinical trial identifier	Phase	Mechanism of action	Disorder	Age range (years)	Primary outcomes measure(s)	Status
EPI‐743	NCT01370447	II	Mitochondrial Redox Modulator	PMD	1+	Change in neuromuscular function, IAE, NPMDS	Active, not recruiting
Vatiquinone (PTC743, EPI‐743)	NCT04378075	II	Mitochondrial Redox Modulator	PMD with Refractory Epilepsy	≤18	Change from baseline in number of observable motor seizures per 28 days, number of disease‐related hospital days, number of participants with status epilepticus	Not yet recruiting
Vincerinone (EPI‐743)	NCT02352896	II	Mitochondrial Redox Modulator	Leigh Syndrome	1–18	Long term effect on disease severity measured by NPMDS	Active, not recruiting
KH176 (Sonlicromanol)	NCT04165239	II	Mitochondrial Redox Modulator	MELAS, MIDD, MM, PMD	18+	Cognitive function: attention domain	Recruiting
Idebenone (Raxone)	NCT02774005	IV	Mitochondrial Redox Modulator	LHON	12+	Proportion of eyes with clinically relevant recovery of visual acuity from baseline	Active, not recruiting
Idebenone (Raxone)	NCT02771379	PASS	Mitochondrial Redox Modulator	LHON	Child, Adult, Older Adult	Long‐term safety profile ‐ IAE	Recruiting
Nicotinamide Riboside	NCT03432871	N/A	NAD Modulator Mitochondrial Biogenesis Enhancer	MELAS, MM, PEO, PMD	18‐70	Bioavailability—pharmacokinetics. Safety—IAE, change in blood analytes, temperature, blood pressure, pulse. Mitochondrial biogenesis31P‐MRS, respiratory chain enzyme analysis, mtDNA copy number	Recruiting
KL1333	NCT03888716	I	NAD Modulator Mitochondrial Biogenesis Enhancer	MELAS, MM, MRCD, PMD, HV	18‐75	IAE, ECG, incidence of abnormal vital signs, incidence of abnormal physical examinations	Recruiting
REN001	NCT03862846	I	Mitochondrial Biogenesis Enhancer	MM	16+	IAE	Active, not recruiting
ABI‐009 (Nab‐sirolimus)	NCT03747328	II	Inhibition of Mitophagy	Leigh/ Leigh‐like Syndrome	2–17	IAE, GMFM	Not yet recruiting
L‐Citrulline	NCT03952234	I	Nitric Oxide Precursor	MELAS	18‐65	Maximal tolerable dose, IAE	Not yet recruiting
Sodium Phenylbutyrate	NCT03734263	I/II	Inhibition of Pyruvate Dehydrogenase Kinase	PDHC Deficiency	0.25‐18	Blood lactate levels	Recruiting
Dichloroacetate	NCT02616484	III	Inhibition of Pyruvate Dehydrogenase Kinase	PDHC Deficiency	0.5‐17	Observer Reported Outcome (ObsRO) measure of health, IAE	Recruiting
Thymidine and Deoxycytidine	NCT03639701	I/II	Nucleosides	Myopathic Thymidine Kinase 2 Deficiency	All	Liver transaminase levels, lymphocyte count, creatinine, ECG, incidence of diarrhoea	Enrolling by invitation
EE‐TP	NCT03866954	II	Erythrocyte Encapsulated ERT	MNGIE	12+	Safety—IAE, laboratory indices, vital signs. Pharmacodynamics—changes in plasma and urine thymidine and deoxyuridine levels. Efficacy— change in body mass index.	Not yet recruiting
CD34+ cells enriched with MNV‐BLD	NCT03384420	I/II	Biological	PMD, PS	Child, Adult, Older Adult	IAE, IPMDS QoL questionnaire	Enrolling by invitation
scAAV2‐P1ND4v2	NCT02161380	I	Gene Therapy	LHON	15+	IAE	Recruiting
GS010 (rAAV2/2‐ND4)	NCT02064569	I/II	Gene Therapy	LHON	18+	IAE	Active, not recruiting
GS010 (rAAV2/2‐ND4)	NCT03293524	III	Gene Therapy	LHON	15+	BCVA	Active, not recruiting
GS010 (rAAV2/2‐ND4)	NCT03406104	III	Gene Therapy	LHON	15+	Long term follow up of gene therapy—IAE	Recruiting
rAAV2‐ND4	NCT03153293	II/III	Gene Therapy	LHON	10‐65	BCVA, computerised visual field	Active, not recruiting

Abbreviations: BCVA, best corrected visual acuity; CPET, cardiopulmonary exercise testing; ECG, electrocardiogram; ERT, enzyme replacement therapy; GMFM, gross motor function measure; HV, healthy volunteers; IAE: incidence of adverse events; IPMDS, international paediatric mitochondrial disease scale; LHON, Leber hereditary optic neuropathy; MDDS, mitochondrial DNA depletion syndrome; MELAS, mitochondrial encephalopathy lactic acidosis and stroke‐like episodes; MIDD, maternally inherited diabetes and deafness; MM, mitochondrial myopathy; MNGIE, mitochondrial neurogastrointestinal encephalopathy; MRCD, mitochondrial respiratory chain deficiency; MRS, magnetic resonance spectroscopy; NPMDS, Newcastle paediatric mitochondrial disease scale; PASS, post‐authorisation safety study; PDHC, pyruvate dehydrogenase complex; PEO, progressive external ophthalmoplegia; PS, Pearson syndrome; QoL, quality of life.

^aSelection of clinical trials for primary mitochondrial disease (PMD) listed in https://clinicaltrials.gov accessed May 22, 2020.