Clinical Trials Logo

Clinical Trial Summary

This is an open-label, multi-centre study in subjects with a genetically confirmed mitochondrial deoxyribonucleic acid (DNA) transfer ribonucleic acid (tRNA)Leu(UUR) m.3243A>G mutation who completed study KH176-202. In the KH176-203 study subjects will be receiving KH176 100 mg BID or KH176 50 mg bid in die (BID) (as determined by the investigator based on safety / tolerability considerations) for a year, thereby ensuring continued treatment with KH176 after study KH176-202. A final follow-up visit is scheduled 4 weeks after the intake of the last dose of study medication for patients not rolling over into the compassionate use program. Primary safety data and secondary efficacy (endpoint) data will be monitored and reviewed every three months by an independent Data Safety Monitoring Board (DSMB) to evaluate potential risks and benefits.


Clinical Trial Description

Mitochondrial diseases, estimated prevalence 1 in 4,300 adults, are caused by pathogenic mutations in genes that ultimately encode mitochondrial proteins of the different enzyme complexes of the oxidative phosphorylation system (OXPHOS). Of these mutations, the 3243> G nucleotide change in the mitochondrially encoded transfer RNALeu (UUR) leucine 1 gene (MT TL 1) is the most prevalent one. When mitochondria are defective, it can result in a wide variety of serious and debilitating diseases, especially in energy-demanding tissues such as the muscles and brain. Therefore, signs and symptoms of mitochondrial disease can include a variety of symptoms such as fatigue, exercise tolerance, muscle weakness, and ataxia, heart failure, deafness, blindness, stunted growth, and cognitive learning disabilities. Despite advances in understanding mitochondrial disease, treatment options are extremely limited and largely supportive to date. Therefore, there is an urgent need for new treatments. KH176, a pharmaceutical ingredient (API), is an orally bioavailable small molecule under development for the treatment of these conditions. KH176 acts as a potent intracellular redox modulating agent targeting the reactive oxygen species as demonstrated in a number of in vitro and in vivo assays. An earlier phase II study showed positive effects of KH176 on alertness and mood. The main objective of the current study is to enable continued treatment with KH176-202 for patients who have completed the KH176-202 study. Since KH176 is expected to be a chronic treatment for mitochondrial diseases, this study will examine long-term safety and explore long-term efficacy. To this end, the highest dose of 100 mg KH176 twice daily (safe and well tolerated by the target group in study KH176-201) will be used as the initial dose, to be administered over 1 year (minimum 365 days). Study KH176-202 uses doses of 50 mg twice daily and 100 mg twice daily. Currently, this study is still blinded, but a review of blinded safety data suggests that these doses are well tolerated. Primary safety data and secondary efficacy (endpoint) data will be monitored and reviewed every three months by an independent Data Safety Monitoring Board (DSMB) to evaluate potential risks and benefits. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04604548
Study type Interventional
Source Khondrion BV
Contact
Status Completed
Phase Phase 2
Start date August 9, 2021
Completion date June 1, 2023

See also
  Status Clinical Trial Phase
Completed NCT03388528 - Low Residue Diet Study in Mitochondrial Disease N/A
Completed NCT04378075 - A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy Phase 2/Phase 3
Completed NCT03678740 - Diagnostic Odyssey Survey 2
Recruiting NCT06051448 - Promoting Resilience in Stress Management (PRISM) and Clinical-focused Narrative (CFN) Pilot in Adults With Primary Mitochondrial Disease (PMD). Phase 1/Phase 2
Completed NCT02909400 - The KHENERGY Study Phase 2
Completed NCT02398201 - A Study of Bezafibrate in Mitochondrial Myopathy Phase 2
Completed NCT03857880 - Identification of New Candidate Genes in Patients With Mitochondrial Disease by High Resolution Chromosome Analysis on DNA Chip
Not yet recruiting NCT06450964 - Establishment of Reproductive Cohort and Prediction Model of Genetic Counseling for Mitochondrial Genetic Diseases
Completed NCT04165239 - The KHENERGYZE Study Phase 2
Completed NCT02284334 - Glycemic Index in Mitochondrial Disease
Recruiting NCT06080568 - Human Mitochondrial Stress-driven Obesity Resistance
Recruiting NCT06080581 - Mitochondrial Dysfunctions Driving Insulin Resistance
Recruiting NCT04802707 - Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome Phase 2
Completed NCT04594590 - Natural History Study of SLC25A46 Mutation-related Mitochondriopathy
Completed NCT04580979 - Natural History Study of FDXR Mutation-related Mitochondriopathy
Withdrawn NCT03866954 - Trial of Erythrocyte Encapsulated Thymidine Phosphorylase In Mitochondrial Neurogastrointestinal Encephalomyopathy Phase 2
Recruiting NCT04113447 - Mitochondrial Donation: An 18 Month Outcome Study.
Enrolling by invitation NCT04734626 - CrCest Study in Primary Mitochondrial Disease
Completed NCT03832218 - Executive Function Disorders and Anxio-depressive Symptomatology in Children and Adolescents With Mitochondrial Pathologies N/A
Terminated NCT02473445 - A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease Phase 2