Open-Label, Dose-Escalating Study to Assess Safety, Tolerability, Efficacy, PK and PD of RP103 in Children With Inherited Mitochondrial Disease (RP103-MITO-001)
Patients (male or female) with either documented genetically confirmed diagnosis of inherited mitochondrial diseases, who are ≥ 2 years old and < 18 years, and meet other specified inclusion and exclusion criteria, will be included in this study.
Patients with inherited mitochondrial diseases associated with nuclear or mitochondrial DNA mutations that impair the respiratory chain. These include, but are not limited to the following clinical syndromes: Leber's hereditary optic neuropathy; myoclonic epilepsy and ragged-red fibers (MERFF); mitochondrial encephalomyopathy, lactic acidosis, and stroke-like syndrome (MELAS); Kearn-Sayre syndrome; subacute necrotizing encephalopathy (Leigh Syndrome); POLG-related disorders (Alpers-Huttenlocher Syndrome, Autosomal Dominant Progressive External Ophthalmoplegia, Autosomal Recessive Progressive External Ophthalmoplegia, Childhood Myocerebrohepatopathy Spectrum Disorders, Myoclonic Epilepsy Myopathy Sensory Ataxia, POLG-Related Ataxia Neuropathy Spectrum Disorders); Mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE), also called myoneurogastrointestinal encephalopathy syndrome or POLIP syndrome; others, e.g., mitochondrial cardiomyopathies and other syndromes due to multiple mitochondrial DNA deletions.
During the pre-screening and screening process, eligibility criteria for each subject will be reviewed by participating Investigators and Raptor's medical officer, in an attempt to ensure all enrolled subjects have a mitochondrial disease with a known genetic mutation (i.e., patients with a clinical presentation and known mitochondrial disease mutations and no variants of uncertain significance). It is anticipated that approximately two-thirds of subjects will have genetically confirmed Leigh Syndrome.
Up to 25 patients will be enrolled if there is no toxicity up to the level of 1.3 g/m2/day of RP103. Initial sample size estimate is 25 subjects. Interim analyses will occur after 4 and then 12 subjects complete the study through Week 24. There is a possibility of stopping for efficacy or for futility after either interim analysis. If the study is not stopped early, final analysis will occur after 25 subjects have completed through Week 24.
The rationale for choosing patients with inherited mitochondrial disease who are age 2 and older is based on available clinical data collected in previous and current RP103 studies in other indications, in subjects aged 2 years and older.
Inherited Mitochondrial Disease, Including Leigh Syndrome
Drug: Cysteamine Bitartrate Delayed-release Capsules (RP103)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Open-Label, Dose-Escalating Study to Assess Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease|
- Change in Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Score [ Time Frame: Baseline vs. Week 24 ] [ Designated as safety issue: No ]Quality of life
- Change over time in Pharmacodynamic Biomarkers [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24 ] [ Designated as safety issue: No ]glutathione, acetoacetate, beta-hydroxybutyrate, lactate
|Study Start Date:||June 2014|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
|Experimental: RP103||Drug: Cysteamine Bitartrate Delayed-release Capsules (RP103)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT02023866
|United States, California|
|University of California at San Diego (UCSD)|
|San Diego, California, United States, 92093-0935|
|Stanford, California, United States, 94305|
|United States, Ohio|
|Akron Children's Hospital|
|Akron, Ohio, United States, 44308|
|United States, Texas|
|Baylor College of Medicine|
|Houston, Texas, United States, 77030|
|United States, Utah|
|University of Utah, Division of Medical Genetics|
|Salt Lake City, Utah, United States, 84132|
|Principal Investigator:||Bruce H. Cohen, MD||Akron Children's Hospital|