Ignite Creation Date:
2024-05-06 @ 3:20 PM
Last Modification Date:
2025-12-17 @ 8:47 AM
Study NCT ID:
NCT04604548
Status:
None
Last Update Posted:
2024-03-06 00:00:00
First Post:
2020-06-19 00:00:00
Brief Title:
The KHENEREXT Study
Sponsor:
Khondrion BV
Organization:
Khondrion BV
Study Overview
Official Title:
A Phase IIb Open-label, Multi-centre, Extension Study to Explore the Long-term Safety and Efficacy of KH176 in Subjects With a Genetically Confirmed Mitochondrial DNA tRNALeu(UUR) m.3243A>G Mutation Who Have Completed the KHENERGYZE Study KH176-202.
Status:
None
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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.
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.
Detailed Description:
Mitochondrial diseases estimated prevalence 1 in 4300 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
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None