Principal Investigator: Nicola Longo
Keywords: Mitochondrial , Melas , Leigh Syndrome Department: Pediatric Genetics
IRB Number: 00084958 Co Investigator:  
Specialty: Pediatric Genetics
Sub Specialties: Medical Genetics
Recruitment Status: Recruiting

Contact Information

Carrie Bailey

Brief Summary

Primary Objective:
• To evaluate safety, tolerability and efficacy of RP103 administered up to 1.3 g/m2/day in two divided doses, every 12 hours, for up to 6 months in subjects with inherited mitochondrial disease.
Secondary Objective:
• To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of RP103 at steady state, in with inherited mitochondrial disease on a stable dose of RP103.
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.

Inclusion Criteria

1. Age 2: > 6 years and < 18 years.
2. Body weight 2: 5 kgs.
3. Documented (genetically confirmed known mutation, i.e. no variants of uncertain significance) diagnosis of inherited mitochondrial disease other than Friedreich's ataxia (FRDA).
4.Moderate disease severity based on Newcastle Pediatric Mitochondrial Disease Scale (NPMDS) score, with a total score of Sections I-III between 15 to 45 inclusive.
a. LHON subjects are exempt of this inclusion criteria but must be approved in writing prior to their enrollment by the Sponsor.
5. For subjects regularly taking dietary supplements such as creatinine, alpha-lipoic acid, CoQ10, vitamin B, camitine, etc. they have to have been taking them for at least 3 months pre-study and will agree to keep these the same throughout the study (from the Screening Visit to Study Exit).
6. With respect to concomitant medications, the subject must:
a) Be willing to abstain from initiating dietary supplements and nonprescribed medications, except as allowed by the Investigator, throughout the study (from the Screening Visit to Study Exit).
b) Be on a stable dose of medications prescribed for seizure management and prevention. Stable dose in this context means unchanged for at least 30 days prior to the Screening Visit.
7. Willing and able to comply with study drug dosing requirements, i.e. ingest the RP103 capsules intact, or sprinkled in liquid or soft food, or using a g-tube.
8. Sexually active female subjects of childbearing potential (i.e., not surgically sterile [tubal ligation, hysterectomy, or bilateral oophorectomy]) must agree to utilize two of the following acceptable methods of contraception throughout the study (from the Screening Visit to Study Exit):
a) Hormonal contraception: birth control pills, injection, patch, vaginal ring or
b) Condom or diaphragm, with spermicide;
c) Intrauterine device (IUD)
d) Sterile male partner (vasectomy performed at least 6 months prior to the
9. Subject's legally authorized representative must provide written informed consent; Subject must provide assent, if required by local/institutional requirements.
10. Have mitochondrial myopathy as evidenced by one or more of the following criteria:
a. Weakness consistent with myopathy (e.g. accompanied by muscle wasting and/or absence of neuropathy) on physical exam
b. OR documented myopathy on the basis of muscle biopsy consistent with mitochondrial myopathy disease
c. OR weakness and/or progressive exercise intolerance (in which modest exercise typically provokes heaviness, weakness, aching of active muscles, or tachycardia). Weakness should be due to myopathy and not neuropathy or other causes as deemed by investigator

Exclusion Criteria

1. Documented diagnosis of concurrent inborn errors of metabolism.
2. Non-elective hospitalization related to mitochondrial disease or direct complication of disease within 60 days prior to the Screening Visit.
3. Platelet count, lymphocyte count or hemoglobin below the lower limit of normal (LLN) at the Screening Visit.
4. Hepatic insufficiency with liver enzyme tests (alkaline phosphatase, AST or ALT) greater than 2.5 times the upper limit of normal (ULN) at the Screening Visit.
5. Bilirubin > 1.2 g/dl at the Screening Visit.
6. Inability to complete the elements of the study, e.g., coma, hemodynamic instability or requiring continuous ventilator support.
7. Malabsorption requiring TPN, chronic diarrhea, bouts of pseudo obstruction.
8. Severe end-organ hypo-perfusion syndrome secondary to cardiac failure resulting in lactic acidosis.
9. Subjects with suspected elevated intracranial pressure, pseudotumor cerebri (PTC) and/or papilledema.
10. Severe gastrointestinal disease including gastroparesis.
11 . History of angina, myocardial infarction, or cardiac surgery within 2 years prior to the Screening Visit.
12. Any clinically significant ECG, including dysrhythmia, or clinically significant abnormal laboratory finding not already listed above at the Screening Visit.
13. History of drug or alcohol abuse.
14. History of pancreatitis.
15. Participated in an investigational drug trial within 30 days or, within 90 days for a biologic, device, or surgical treatment, for inherited mitochondrial diseases prior to the Screening Visit.
16. Known or suspected hypersensitivity to cysteamine and penicillamine.
17. Female subjects who are nursing, planning a pregnancy, known or suspected to be pregnant, or with a positive serum pregnancy test at the Screening Visit.
18. Subjects who, in the opinion of the Investigator, are not able or willing to comply with the protocol.