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

NCT02473445 | Terminated Phase 2 Results

• 1 other identifier: RP103-MITO-002
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 5

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).

Conditions

Mitochondrial Diseases

Keywords

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)

Outcome Measures

Primary Outcomes (1)

• Change in Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Score

  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.

  Baseline, every 3 months and Study Exit (up to 24 Months)

Secondary Outcomes (2)

• Change Over Time in Two of the Most Pre-eminent Symptoms

  Baseline, every 3 months and Study Exit (up to 24 Months)

• Change Over Time in Pharmacodynamic Biomarkers

  Baseline, every 3 months and Study Exit (up to 24 Months)

Study Arms (1)

Cysteamine Bitartrate Delayed-release

EXPERIMENTAL

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

Interventions

Cysteamine Bitartrate DRUG

Cysteamine Bitartrate Delayed-release capsules

Also known as: RP103, PROCYSBI®

Cysteamine Bitartrate Delayed-release

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Completed all visits in Study RP103-MITO-001 (NCT02023866).
• Body weight ≥ 5 kg.
• 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).
• 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.
• 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).
• Patient's legally authorized representative must provide written informed consent; Patient must provide assent, if required by local/institutional requirements.

You may not qualify if:

• Documented diagnosis of concurrent inborn errors of metabolism.
• Platelet count, lymphocyte count or hemoglobin below the lower limit of normal (LLN) at the Baseline visit.
• 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.
• Bilirubin \> 1.2 g/dL at the Baseline Visit.
• Inability to complete the elements of the study, e.g., coma, hemodynamic instability or requiring continuous ventilator support.
• Malabsorption requiring total parenteral nutrition (TPN), chronic diarrhea, bouts of pseudo obstruction.
• Severe end-organ hypo-perfusion syndrome secondary to cardiac failure resulting in lactic acidosis.
• Patients with suspected elevated intracranial pressure, pseudotumor cerebri (PTC) and/or papilledema.
• Severe gastrointestinal disease including gastroparesis.
• History of drug or alcohol abuse.
• History of pancreatitis.
• 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.
• Known or suspected hypersensitivity to cysteamine and penicillamine.
• 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.
• Patients who, in the opinion of the Investigator, are not able or willing to comply with the protocol.

Sponsors & Collaborators

• Amgen: lead

Study Sites (5)

University of California at San Diego (UCSD)

San Diego, California, 92093-0935, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (4)

• Bousquet M, Gibrat C, Ouellet M, Rouillard C, Calon F, Cicchetti F. Cystamine metabolism and brain transport properties: clinical implications for neurodegenerative diseases. J Neurochem. 2010 Sep;114(6):1651-8. doi: 10.1111/j.1471-4159.2010.06874.x. Epub 2010 Aug 19.

  PMID: 20569301 BACKGROUND

• Salmi H, Leonard JV, Rahman S, Lapatto R. Plasma thiol status is altered in children with mitochondrial diseases. Scand J Clin Lab Invest. 2012 Apr;72(2):152-7. doi: 10.3109/00365513.2011.646299. Epub 2012 Jan 2.

  PMID: 22208644 BACKGROUND

• Maher P, Lewerenz J, Lozano C, Torres JL. A novel approach to enhancing cellular glutathione levels. J Neurochem. 2008 Nov;107(3):690-700. doi: 10.1111/j.1471-4159.2008.05620.x. Epub 2008 Aug 12.

  PMID: 18702664 BACKGROUND

• Mancuso M, Orsucci D, Logerfo A, Rocchi A, Petrozzi L, Nesti C, Galetta F, Santoro G, Murri L, Siciliano G. Oxidative stress biomarkers in mitochondrial myopathies, basally and after cysteine donor supplementation. J Neurol. 2010 May;257(5):774-81. doi: 10.1007/s00415-009-5409-7. Epub 2009 Dec 4.

  PMID: 19960200 BACKGROUND

MeSH Terms

Conditions

Mitochondrial Diseases; Leigh Disease; Optic Atrophy, Hereditary, Leber; Epilepsies, Myoclonic; Mitochondrial Encephalomyopathies; Acidosis, Lactic; Ophthalmoplegia, Chronic Progressive External; Visceral myopathy familial external ophthalmoplegia

Interventions

Cysteamine

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pyruvate Metabolism, Inborn Errors; Carbohydrate Metabolism, Inborn Errors; Optic Atrophies, Hereditary; Optic Atrophy; Optic Nerve Diseases; Cranial Nerve Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Eye Diseases, Hereditary; Eye Diseases; Epilepsy, Generalized; Epilepsy; Epileptic Syndromes; Mitochondrial Myopathies; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Acidosis; Acid-Base Imbalance; Ophthalmoplegia; Ocular Motility Disorders; Paralysis; Neurologic Manifestations; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Mercaptoethylamines; Ethylamines; Amines; Organic Chemicals; Sulfhydryl Compounds; Sulfur Compounds

Limitations and Caveats

The study was closed prematurely due to lack of efficacy demonstrated in base study RP103-MITO-001 and no efficacy analyses were conducted.

Results Point of Contact

• Title: Evelyn Olson, Director
• Organization: Horizon Pharma USA, Inc.

clinicaltrials@horizonpharma.com

224- 383-3000

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label extension study

Study Record Dates

• First Submitted: June 10, 2015
• First Posted: June 16, 2015
• Study Start: May 19, 2015
• Primary Completion: March 6, 2017
• Study Completion: March 6, 2017
• Last Updated: December 27, 2024
• Results First Posted: May 11, 2018

Record last verified: 2024-12

Locations

US (5)