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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02023866
• Date of registration: 17/12/2013
• Prospective Registration: Yes
• Primary sponsor: Horizon Pharma USA, Inc.
• Public title: Open-Label, Dose-Escalating Study Assessing Safety, Tolerability, Efficacy, of RP103 in Mitochondrial Disease MITO-001
• Scientific title: An Open-Label, Dose-Escalating 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
• Date of first enrolment: May 2014
• Target sample size: 36
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02023866
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Evelyn Olson, BS
• Affiliation: Horizon Pharma USA, Inc.

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Age = 6 years and < 18 years

2. Body weight = 5 kg

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 score between 15 to 45 inclusive [Leber's Hereditary Optic
Neuropathy (LHON) subjects are exempt of this inclusion criteria], if approved by the
sponsor.

5. For patients regularly taking dietary supplements such as creatinine, alpha-lipoic
acid, coenzyme Q10 (CoQ10), vitamin B, carnitine, 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:

1. Be willing to abstain from initiating dietary supplements and non-prescribed
medications, except as allowed by the Investigator, throughout the study (from
the Screening Visit to Study Exit);

2. 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 forms of contraception throughout the study
(from the Screening Visit to Study Exit):

1. Hormonal contraception: birth control pills, injection, patch, vaginal ring or
implant;

2. Condom or diaphragm, with spermicide;

3. Intrauterine device (IUD)

4. Sterile male partner (vasectomy performed at least 6 months prior to the study).

9. Subjects'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:

1. Weakness consistent with myopathy (e.g. accompanied by muscle wasting and/or
absence of neuropathy) on physical exam

2. OR documented myopathy on the basis of muscle biopsy consistent with
mitochondrial myopathy disease

3. 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, aspartate
aminotransferase [AST] or alanine aminotransferase [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 total parenteral nutrition (TPN), chronic diarrhea, bouts of
pseudo obstruction

8. Severe end-organ hypo-perfusion syndrome secondary to cardiac failure resulting in
lactic acidosis

9. Patients 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 electrocardiogram (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. Subject's who, in the opinion of the Investigator, are not able or willing to comply
with the protocol.



Age minimum: 6 Years
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Inherited Mitochondrial Disease, Including Leigh Syndrome

Intervention(s)

Drug: Cysteamine Bitartrate

Primary Outcome(s)

Change From Baseline in Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Sections I-IV [Time Frame: Baseline through Week 24]

Secondary Outcome(s)

Change From Baseline in Glutathione Disulfide [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24]

Change From Baseline in 6 Minute Walk Test [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24]

Change From Baseline in Friedreich Ataxia Rating Scale [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24]

Change From Baseline in Glutathione [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24]

Change From Baseline in Jamar Dynamometer Hand Strength [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24]

Change From Baseline in Lactic Acid [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24]

Change From Baseline in Barry-Albright Dystonia Scale Total Score [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24]

Change From Baseline in Gross Motor Function [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24]

Change From Baseline in Modified Lansky Play Performance Scale [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24]

Secondary ID(s)

RP103-MITO-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 13/11/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02023866