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

NCT ID: NCT02473445

Last Updated: 2024-12-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-19
• Study Completion Date: 2017-03-06

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).

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.

Study with completed results acquired from Horizon in 2024.

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)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Cysteamine Bitartrate

Intervention Type: DRUG

Cysteamine Bitartrate Delayed-release capsules

Interventions

Cysteamine Bitartrate

Cysteamine Bitartrate Delayed-release capsules

Intervention Type: DRUG

Other Intervention Names

RP103; PROCYSBI®

Eligibility Criteria

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

University of California at San Diego (UCSD)

San Diego, California, United States

Stanford University School of Medicine

Stanford, California, United States

Akron Children's Hospital

Akron, Ohio, United States

Baylor College of Medicine

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 20569301 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22208644 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18702664 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19960200 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

RP103-MITO-002

Identifier Type: -

Identifier Source: org_study_id