Clinical Trial: Open-Label, Dose-Escalating Study Assessing Safety, Tolerability, Efficacy, of RP103 in Mitochondrial Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 M

Brief Summary: Patients with mitochondrial diseases, who are ≥ 2 years old and < 18 years, will be included in this study. It is anticipated that approximately one half 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. Interim analyses will occur after 4 and then 12 subjects complete the study through Week 24. If the study is not stopped early, final analysis will occur after 25 subjects have completed through Week 24.

Detailed Summary:

This is an open-label, dose-escalation study to assess the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of Cysteamine Bitartrate Delayed-release Capsules (RP103) for treatment of children with inherited mitochondrial disease.

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 strokelike syndrome (MELAS); KearnSayre syndrome; subacute necrotizing encephalopathy (Leigh Syndrome); POLGrelated disorders (Alpers-Huttenlocher Syndrome, Autosomal Dominant Progressive External Ophthalmoplegia, Autosomal Recessive Progressive External Ophthalmoplegia, Childhood Myocerebrohepatopathy Spectrum Disorders, Myoclonic Epilepsy Myopathy Sensory Ataxia, POLGRelated 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.

Prior to treatment, patients will undergo a Screening Visit. If eligible, each subject will return for the Day 1 study visit and begin RP103 dosing on that day. Every 2 weeks over the subsequent 8 weeks, subjects will alternate between returning to the clinic for detailed assessments (Weeks 4 and 8) and receiving a telephone call from the Investigator team to assess safety and RP103 dose (Weeks 2 and 6) and the potential need for an immediate unscheduled study visit. Thereafter, subjects will continue to return to the clinic every 4 w
Sponsor: Horizon Pharma USA, Inc.

Current Primary Outcome: Change in Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Sections I-IV to assess Disease Progression [ Time Frame: Baseline through Week 24 ]

Quality of life


Original Primary Outcome: Change in Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Score [ Time Frame: Baseline vs. Week 24 ]

Quality of life


Current Secondary Outcome:

  • Change over time in Pharmacodynamic Biomarkers [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24 ]
    Glutathione, glutathione disulfide, and lactate
  • Change over time in two of the most preeminent symptoms [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24 ]
    Myopathy, Dystonia, Ataxia, Retarded motor development, Reduced activities of daily living, Vision


Original Secondary Outcome: Change over time in Pharmacodynamic Biomarkers [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24 ]

glutathione, acetoacetate, beta-hydroxybutyrate, lactate


Information By: Horizon Pharma USA, Inc.

Dates:
Date Received: December 17, 2013
Date Started: June 2014
Date Completion:
Last Updated: April 11, 2017
Last Verified: April 2017