Table 2.
Summary of the historic and current disease specific pharmacological therapeutic landscape for in mitochondrial disease.
| Disease(s)/syndrome(s) investigated | Pharmacological agent | Trial phase | Description | N | Most recent update | Status/result | Trial ID |
|---|---|---|---|---|---|---|---|
| Childhood PMD | Cysteamine | 2 | Safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics | 36 | 2017 | Terminated (lack of effect) | NCT02023866 |
| EPI-743 | 1/2 | Crossover trial to investigate efficacy | 20 | 2020 | Completed | NCT01642056 | |
| Leigh and Leigh-like | ABI-009 | 2a | Safety, tolerability and efficacy | 32 | 2020 | Not yet recruiting | NCT03747328 |
| EPI-743 | 2 | Safety, tolerability and efficacy | 30 | 2020 | Active, not recruiting | NCT02352896 | |
| KL1333 | 1 | Safety | 30 (C) | 2016 | Completed | NCT02544217 | |
| LHON | Elamipretide | 2 | Safety, tolerability and efficacy | 12 | 2019 | Completed | NCT02693119 |
| Idebenone | 4 | Efficacy (long term follow-up) | 250 | 2019 | Active, not recruiting | NCT02774005 | |
| 4 | Safety (long term follow-up) | 250 | 2020 | Active, not recruiting | NCT02771379 | ||
| 4 | Expanded access | NA | 2020 | Available | NCT04381091 | ||
| 2 | Safety, tolerability and efficacy | 85 | 2013 | Completed | NCT00747487 | ||
| KL1333 | 1 | Safety | 30 (C) | 2016 | Completed | NCT02544217 | |
| m.3243A<G | Acipimox | 2a/2b | Adaptive design; single centre | 80-120 | 2020 | Recruiting | ISRCTN12895613 |
| KL1333 | 1 | Safety | 30 (C) | 2016 | Completed | NCT02544217 | |
| ME | KH176 | 2 | Safety, tolerability and efficacy | 20 (C) | 2018 | Completed | NCT02909400 |
| KL1333 | 2 | Safety, tolerability and efficacy | 27 (C) | 2020 | Recruiting | NCT04165239 | |
| MELAS | Dichloroacetic acid | 2 | Treatment | 35 | 2005 | Terminated (peripheral nerve toxicity) | NCT00068913 |
| Idebenone | 2 | Treatment | 27 | 2016 | Completed | NCT00887562 | |
| KH176 | 2 | Safety, tolerability and efficacy | 20 (C) | 2018 | Completed | NCT02909400 | |
| KL1333 | 1 | Safety | 30 (C) | 2016 | Completed | NCT02544217 | |
| 2 | Safety, tolerability and efficacy | 27 (C) | 2020 | Recruiting | NCT04165239 | ||
| MIDD | KH176 | 2 | Safety, tolerability and efficacy | 20 (C) | 2018 | Completed | NCT02909400 |
| KL1333 | 1a/1b | Safety, tolerability, pharmacokinetics and pharmacodynamics | 72 (C) | 2019 | Recruiting | NCT03888716 | |
| mDNA depletion | Thymidine and deoxycytidine | 1/2 | Safety, tolerability and efficacy | 20 | 2019 | Enrolling by invitation | NCT03639701 |
| Mitochondrial respiratory chain deficiencies | EPI-743 | 2 | Palliative expanded access protocol | 94 | 2020 | Active, not recruiting | NCT01370447 |
| KL1333 | 1a/1b | Safety, tolerability, pharmacokinetics and pharmacodynamics | 72 (C) | 2019 | Recruiting | NCT03888716 | |
| Pearson | EPI-743 | 2 | Safety, tolerability and efficacy | 2 | 2018 | Terminated | NCT02104336 |
| PMD | Bezafibrate | 2 | Treatment | 6 | 2017 | Awaiting results | NCT02398201 |
| KL1333 | 2 | Safety, tolerability and efficacy | 27 (C) | 2020 | Recruiting | NCT04165239 | |
| Elamipretide | 2 | Safety, tolerability and efficacy | 36 | 2020 | Terminated | NCT02976038 | |
| 2 | Safety, tolerability and efficacy | 30 | 2017 | Completed | NCT02805790 | ||
| 2 | Prospective observational | 215 | 2019 | Completed | NCT03048617 | ||
| KH176 | 2 | Safety, tolerability and efficacy | 20 (C) | 2018 | Completed | NCT02909400 | |
| KL1333 | 1 | Safety | 30 (C) | 2016 | Completed | NCT02544217 | |
| 1a/1b | Safety, tolerability, pharmacokinetics and pharmacodynamics | 72 (C) | 2019 | Recruiting | NCT03888716 | ||
| PMM | Elamipretide | 3 | Safety, tolerability and efficacy | 218 | 2020 | Failed (did not meet primary end-point) | NCT03323749 |
| KH176 | 2 | Safety, tolerability and efficacy | 20 (C) | 2018 | Completed | NCT02909400 | |
| KL1333 | 2 | Safety, tolerability and efficacy | 27 (C) | 2020 | Recruiting | NCT04165239 | |
| 1a/1b | Safety, tolerability, pharmacokinetics and pharmacodynamics | 72 (C) | 2019 | Recruiting | NCT03888716 | ||
| REN001 | 1 | Safety | 23 | 2020 | Not reported | NCT03862846 | |
| RTA 408 | 2 | Safety, efficacy and pharmacodynamics | 53 | 2018 |
Completed Results not reported |
NCT02255422 | |
| PCDC | Dichloroacetic acid | 3 | Treatment | 9 | 2020 | Recruiting | NCT02616484 |
Recruiting trials as of August 2020 are indicated in bold. Please note some trials investigate therapy in multiple disorders
C combined clinical trial investigating multiple primary mitochondrial diseases, LHON Leber's hereditary optic neuropathy, ME myalgic encephalomyelitis, MELAS mitochondrial encephalopathy lactic acidosis and stroke-like episodes, N number of participants recruited lactic acidosis and stroke-like episodes, MIDD maternally inherited diabetes-deafness syndrome, PCDD pyruvate dehydrogenase complex deficiency, PMD primary mitochondrial disease, PMM primary mitochondrial myopathies