Recruitment

Recruitment Status
Not yet recruiting
Estimated Enrollment
Same as current

Summary

Conditions
  • Chronic Progressive External Ophthalmoplegia (CPEO)
  • Maternally Inherited Diabetes and Deafness (MIDD)
  • Mitochondrial Diseases
  • Mitochondrial DNA tRNALeu(UUR) m.3243A<G Mutation
  • Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke Like Episodes (MELAS)
Type
Interventional
Phase
Phase 2
Design
Allocation: N/AIntervention Model: Single Group AssignmentIntervention Model Description: Open LabelMasking: None (Open Label)Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

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 mitoc...

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.

Tracking Information

NCT #
NCT04604548
Collaborators
  • Julius Clinical, The Netherlands
  • ProPharma Group
  • Author
Investigators
Not Provided