Mitochondrial DiseasesPhase 2NCT02473445
A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease
A Phase 2 study testing Cysteamine Bitartrate in people with Mitochondrial Diseases, run by Amgen at 5 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Mitochondrial Diseases
- What is being tested?
- Cysteamine Bitartrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 5 sitesUnited States
- Study dates
- 19 May 2015to 6 Mar 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Akron Children's Hospital
Akron, Ohio, 44308
Baylor College of Medicine
Houston, Texas, 77030
University of Utah
Salt Lake City, Utah, 84132
University of California at San Diego (UCSD)
San Diego, California, 92093-0935
Stanford University School of Medicine
Stanford, California, 94305
About this study
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
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).
Read the 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
- Being tested
- Cysteamine Bitartrate
- 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)
- Medical subject headings
- Mitochondrial Diseases, Leigh Disease, Optic Atrophy, Hereditary, Leber, Epilepsies, Myoclonic, Mitochondrial Encephalomyopathies, Acidosis, Lactic, Ophthalmoplegia, Chronic Progressive External, Visceral myopathy familial external ophthalmoplegia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cysteamine BitartrateDrug
Also called RP103, PROCYSBI®
Cysteamine Bitartrate Delayed-release capsules
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Cysteamine Bitartrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: Baseline, every 3 months and Study Exit (up to 24 Months)
Change Over Time in Pharmacodynamic Biomarkers
Change from baseline in glutathione, glutathione disulfide, and lactate analyses were not performed as the study was prematurely terminated.
Measured: Baseline, every 3 months and Study Exit (up to 24 Months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2015 (estimated)
- Study start19 May 2015
- Primary completion6 Mar 2017
- Study completion6 Mar 2017
Why it stopped: Sponsor decision to end development of RP103 for mitochondrial disease due to lack of efficacy demonstrated in base study RP103-MITO-001.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Mitochondrial DiseasesStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label extension study
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02473445
- Sponsor's protocol ID
- RP103-MITO-002
- Status last verified
- Dec 2024
- First submitted
- 10 Jun 2015
- Last updated
- 27 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 20569301Salmi 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.
PubMed 22208644Maher 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.
PubMed 18702664Mancuso 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.
PubMed 19960200
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02473445
- Acronym / sponsor ID
- RP103-MITO-002
- 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)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision to end development of RP103 for mitochondrial disease due to lack of efficacy demonstrated in base study RP103-MITO-001.
- Enrolment
- 22 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 19 May 2015 (actual)
- Primary completion
- 6 Mar 2017 (actual)
- Study completion
- 6 Mar 2017 (actual)
- First posted
- 16 Jun 2015 (estimated)
- Results
- Posted 11 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label extension study
| Arm | Type | Receives |
|---|---|---|
| Cysteamine Bitartrate Delayed-release | Experimental | Drug: Cysteamine BitartrateParticipants 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. |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- 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):
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cysteamine BitartrateAlso: RP103, PROCYSBI®Cysteamine Bitartrate Delayed-release capsules | Drug | Cysteamine Bitartrate Delayed-release |
Primary outcome
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.
2 secondary outcomes
Change Over Time in Two of the Most Pre-eminent Symptoms
Time frame: Baseline, every 3 months and Study Exit (up to 24 Months)
Change Over Time in Pharmacodynamic Biomarkers
Time frame: Baseline, every 3 months and Study Exit (up to 24 Months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20569301Bousquet 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.
- Background: PubMed 22208644Salmi 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.
- Background: PubMed 18702664Maher 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.
- Background: PubMed 19960200Mancuso 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cysteamine Bitartrate in people with Mitochondrial Diseases, run by Amgen at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Score (time frame: Baseline, every 3 months and Study Exit (up to 24 Months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02473445, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2024.