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A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease

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ClinicalTrials.gov Identifier: NCT02473445
Recruitment Status : Terminated (Sponsor decision to end development of RP103 for mitochondrial disease due to lack of efficacy demonstrated in base study RP103-MITO-001.)
First Posted : June 16, 2015
Results First Posted : May 11, 2018
Last Update Posted : May 11, 2018
Information provided by (Responsible Party):
Horizon Pharma USA, Inc.

Brief Summary:
A long-term extension study to assess the safety, tolerability and efficacy of cysteamine bitartrate delayed-release capsules (RP103) in children with inherited mitochondrial diseases who previously enrolled into study RP103-MITO-001 (NCT02023866).

Condition or disease Intervention/treatment Phase
Mitochondrial Diseases Drug: Cysteamine Bitartrate Phase 2

Detailed Description:

Patients with inherited mitochondrial diseases associated with nuclear or mitochondrial deoxyribonucleic acid (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); polymerase gamma (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 polyneuropathy-ophthalmoplegia-leukoencephalopathy- Intestinal pseudoobstruction (POLIP) syndrome; others, e.g., mitochondrial cardiomyopathies and other syndromes due to multiple mitochondrial DNA deletions.

Patients completing study RP103-MITO-001 (NCT02023866) are eligible for enrollment into the extension study RP103-MITO-002 if all inclusion and exclusion criteria are fulfilled. Subjects continue on the last total daily dose of cysteamine bitartrate delayed-release capsules taken during RP103-MITO-001. Dose-adjustments are permitted.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Open-label extension study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Long-Term Open-Label Extension Study of RP103-MITO-001 to Assess the Safety, Tolerability and Efficacy of Cysteamine Bitartrate Delayed-release Capsules (RP103) for Treatment of Children With Inherited Mitochondrial Disease
Actual Study Start Date : May 19, 2015
Actual Primary Completion Date : March 6, 2017
Actual Study Completion Date : March 6, 2017

Arm Intervention/treatment
Experimental: Cysteamine Bitartrate Delayed-release
Participants received cysteamine bitartrate delayed-release capsules (RP103) twice daily for up to 2 years. The starting dose was the same as the last dose received in study RP103-MITO-001, the maximum dose was 1.3 g/m²/day.
Drug: Cysteamine Bitartrate
Cysteamine Bitartrate Delayed-release capsules
Other Names:
  • RP103

Primary Outcome Measures :
  1. Change in Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Score [ Time Frame: Baseline, every 3 months and Study Exit (up to 24 Months) ]

    The NPMDS evaluates the progression of mitochondrial disease in pediatric patients in 4 domains:

    I - Current Function (vision, hearing, communication, feeding, and mobility) with scores ranging from 0 to 21;

    II - System Specific Involvement (seizures, encephalopathy, bleeding diathesis or coagulation defects, gastrointestinal, endocrine, respiratory, cardiovascular, renal, liver, and blood) with scores ranging from 0 to 30.

    III - Current Clinical Assessment (growth and development over past 6 months, vision, strabismus and eye movement, myopathy, ataxia, pyramidal, extrapyramidal, and neuropathy) with scores ranging from 0 to 28;

    IV - Quality of Life with scores ranging from 0 to 25. For sections I-III, higher scores reflect more severe disease. For Section IV, a higher score reflects a lower quality of life.

Secondary Outcome Measures :
  1. Change Over Time in Two of the Most Pre-eminent Symptoms [ Time Frame: Baseline, every 3 months and Study Exit (up to 24 Months) ]
    The two pre-eminent symptoms previously identified in study RP103-MITO-001 were to be continued to be assessed during the extension study. Symptoms included myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision.

  2. Change Over Time in Pharmacodynamic Biomarkers [ Time Frame: Baseline, every 3 months and Study Exit (up to 24 Months) ]
    Change from baseline in glutathione, glutathione disulfide, and lactate analyses were not performed as the study was prematurely terminated.

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Completed all visits in Study RP103-MITO-001 (NCT02023866).
  2. Body weight ≥ 5 kg.
  3. The subject must be willing to abstain from initiating dietary supplements and non-prescribed medications except as allowed by the Investigator, throughout the study (from Day 1 to Study Exit).
  4. 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.
  5. 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 Day 1 to Study Exit):

    • Hormonal contraception: birth control pills, injection, patch, vaginal ring or implant;
    • Condom or diaphragm, with spermicide;
    • Intrauterine device (IUD);
    • Sterile male partner (vasectomy performed at least 6 months prior to the study).
  6. Patient's legally authorized representative must provide written informed consent; Patient must provide assent, if required by local/institutional requirements.

Exclusion Criteria:

  1. Documented diagnosis of concurrent inborn errors of metabolism.
  2. Platelet count, lymphocyte count or hemoglobin below the lower limit of normal (LLN) at the Baseline visit.
  3. 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 Baseline Visit.
  4. Bilirubin > 1.2 g/dL at the Baseline Visit.
  5. Inability to complete the elements of the study, e.g., coma, hemodynamic instability or requiring continuous ventilator support.
  6. Malabsorption requiring total parenteral nutrition (TPN), chronic diarrhea, bouts of pseudo obstruction.
  7. Severe end-organ hypo-perfusion syndrome secondary to cardiac failure resulting in lactic acidosis.
  8. Patients with suspected elevated intracranial pressure, pseudotumor cerebri (PTC) and/or papilledema.
  9. Severe gastrointestinal disease including gastroparesis.
  10. History of drug or alcohol abuse.
  11. History of pancreatitis.
  12. Participated in an investigational drug trial (except the RP103-MITO-001 study) within 30 days or, within 90 days for a biologic, device, or surgical treatment, for inherited mitochondrial diseases prior to the Baseline Visit.
  13. Known or suspected hypersensitivity to cysteamine and penicillamine.
  14. Female subjects who are nursing, planning a pregnancy, known or suspected to be pregnant, or with a positive serum pregnancy test at the Baseline visit.
  15. Patients who, in the opinion of the Investigator, are not able or willing to comply with the protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02473445

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United States, California
University of California at San Diego (UCSD)
San Diego, California, United States, 92093-0935
Stanford University School of Medicine
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
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Horizon Pharma USA, Inc.
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Study Director: Evelyn Olson, BS Horizon Pharma USA, Inc.
  Study Documents (Full-Text)

Documents provided by Horizon Pharma USA, Inc.:
Study Protocol  [PDF] December 16, 2014
Statistical Analysis Plan  [PDF] October 16, 2017

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Responsible Party: Horizon Pharma USA, Inc.
ClinicalTrials.gov Identifier: NCT02473445    
Other Study ID Numbers: RP103-MITO-002
First Posted: June 16, 2015    Key Record Dates
Results First Posted: May 11, 2018
Last Update Posted: May 11, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Horizon Pharma USA, Inc.:
Inherited mitochondrial disease
Leigh Syndrome
Leber's Hereditary Optic Neuropathy (LHON)
Myoclonic epilepsy and ragged-red fibers (MERFF)
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like syndrome (MELAS)
Kearn-Sayre syndrome
Polymerase gamma (POLG) -related disorders
Mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE)
Additional relevant MeSH terms:
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Mitochondrial Diseases
Metabolic Diseases
Cystine Depleting Agents
Molecular Mechanisms of Pharmacological Action