Trial Outcomes & Findings for 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 NCT02473445)

Last Updated: 2024-12-27

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

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

Results posted on

2024-12-27

Participant Flow

Participants who completed study RP103-MITO-001 (NCT02023866) study were eligible for enrollment into this extension study. The study was conducted at 5 sites in the United States.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	22
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	22

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Withdrawal by Subject	2
Overall Study Sponsor Decision	20

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cysteamine Bitartrate Delayed-release n=22 Participants 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.
Age, Continuous	10.8 years STANDARD_DEVIATION 4.5 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants
Race/Ethnicity, Customized Black of African American	0 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=5 Participants
Race/Ethnicity, Customized White	18 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	2 Participants n=5 Participants

PRIMARY outcome

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

Population: The study was closed prematurely due to lack of efficacy demonstrated in base study RP103-MITO-001. As a result, only a limited amount of data was collected for patients that were enrolled prior to termination. The decision was made that the data were not complete enough, and no analyses were conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

Cysteamine Bitartrate Delayed-release

Serious events: 9 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cysteamine Bitartrate Delayed-release n=22 participants at risk 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.
Eye disorders Blepharospasm	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Gastrointestinal disorders Diarrhoea	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Gastrointestinal disorders Vomiting	9.1% 2/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Infections and infestations Clostridium difficile infection	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Infections and infestations Device related infection	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Infections and infestations Influenza	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Infections and infestations Parainfluenzae virus infection	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Infections and infestations Respiratory syncytial virus bronchiolitis	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Infections and infestations Rhinovirus infection	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Infections and infestations Urosepsis	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Metabolism and nutrition disorders Dehydration	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Musculoskeletal and connective tissue disorders Mobility decreased	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Musculoskeletal and connective tissue disorders Muscle twitching	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Nervous system disorders Ataxia	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Nervous system disorders Convulsion	9.1% 2/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Nervous system disorders Muscle spasticity	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Nervous system disorders Status epilepticus	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Psychiatric disorders Confusional state	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Respiratory, thoracic and mediastinal disorders Cough	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Respiratory, thoracic and mediastinal disorders Hypercapnia	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Respiratory, thoracic and mediastinal disorders Hypoxia	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Respiratory, thoracic and mediastinal disorders Respiratory distress	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	4.5% 1/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.

Other adverse events

Other adverse events
Measure	Cysteamine Bitartrate Delayed-release n=22 participants at risk 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.
Gastrointestinal disorders Abdominal pain	9.1% 2/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Gastrointestinal disorders Nausea	9.1% 2/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Gastrointestinal disorders Vomiting	50.0% 11/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
General disorders Asthenia	9.1% 2/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
General disorders Pyrexia	22.7% 5/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Nervous system disorders Ataxia	9.1% 2/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Nervous system disorders Convulsion	9.1% 2/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Nervous system disorders Headache	9.1% 2/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Nervous system disorders Lethargy	9.1% 2/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Nervous system disorders Myoclonus	9.1% 2/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.
Respiratory, thoracic and mediastinal disorders Nasal congestion	9.1% 2/22 • From first dose of study drug until the last dose; median duration of treatment was 238 days.

Additional Information

Evelyn Olson, Director

Horizon Pharma USA, Inc.

Phone: 224- 383-3000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Horizon requests that any Investigator/institution that plans on presenting or publishing results provide written notification of their request a minimum of 60 days prior to presentation or publication. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsors' Intellectual Property rights .
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Restriction type: OTHER