CystinosisPhase 3NCT01197378
Long-Term Safety Follow-up Study of Cysteamine Bitartrate Delayed-release Capsules (RP103)
A Phase 3 study testing Cysteamine Bitartrate Delayed-release Capsules in people with Cystinosis, run by Amgen at 10 sites in 3 countries.
Trial summary
Cystinosis is an inherited disease that if untreated, results in kidney failure as early as the first decade of life. The current marketed therapy is Cystagon® (cysteamine bitartrate immediate release) which must be taken every six hours for the rest of the patient's life to prevent complications of cystinosis. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Cystinosis
- What is being tested?
- Cysteamine Bitartrate Delayed-release Capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 10 sitesin 3 countries
- Study dates
- 27 Aug 2010to 26 Jun 2017
- Phase
- Phase 3
- 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 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male and female subjects must have completed the last visit of Study RP103-03 and be willing to continue with RP103 treatment.
- OR for patients who did not complete the RP103-03 study:
- Male and female subjects must have cystinosis.
- Subjects must be on a stable dose of Cystagon® at least 21 days prior to Screening.
- Within the last 6 months, no clinically significant change from normal in liver function tests (i.e., alanine aminotransferase [ALT], aspartate aminotransferase [AST], total bilirubin) and renal function (i.e., estimated glomerular filtration rate [eGFR]) at Screening as determined by the Investigator.
- Subjects with an eGFR corrected for body surface area > 30 mL/min/1.73m².
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- Sexually active female subjects of childbearing potential (i.e., not surgically sterile [tubal ligation, hysterectomy, or bilateral oophorectomy] or at least 2 years naturally postmenopausal) must agree to utilize the same acceptable form of contraception from Screening through completion of the study.
- Subjects must be willing and able to comply with the study restrictions and requirements.
- Subjects or their parent or guardian must provide written informed consent and assent (where applicable) prior to participation in the study.
Who cannot join
- Patients enrolled in the previous Study RP103-03 who did not complete their last scheduled Study visit or who do not wish to continue on treatment with RP103.
- AND for patients who did not complete the RP103-03 study:
- Subjects less than 1 year old
- Subjects with a known history, currently of the following conditions or other health issues that make it, in the opinion of the investigator, unsafe for them to participate: inflammatory bowel disease (if currently active) or have had prior resection of small intestine; Heart disease (e.g., myocardial infarction, heart failure, unstable arrhythmias or poorly controlled hypertension) 90 days prior to Screening; Active bleeding disorder 90 days prior to Screening; Malignant disease within the last 2 years.
- Patients with a hemoglobin level < 10 g/dL at Screening or a level that, in the opinion of the investigator, makes it unsafe for the subject to participate.
- Subjects with known hypersensitivity to cysteamine or penicillamine.
- Female subjects who are nursing, planning a pregnancy, known or suspected to be pregnant, or have a positive serum pregnancy screen.
- Subjects who, in the opinion of the Investigator, are not able or willing to comply with the protocol.
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
United States5 sites
Emory Children's Center
Atlanta, Georgia, 30322
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60614
Texas Children's Hospital/Baylor University
Houston, Texas, 77030
California Pacific Medical Center (CPMC) Research Institute
San Francisco, California, 94115
Stanford University Medical School
Stanford, California, 94305
France4 sites
Hospices Civils de Lyon
Lyon
Hôpital Arnaud Villeneuve - CHU Montpellier
Montpellier
Hopital Necker
Paris
Robert Debre Hospital
Paris
About this study
Official title: A Long-Term, Open-Label, Safety and Efficacy Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Patients With Cystinosis
Cystinosis is an inherited disease that if untreated, results in kidney failure as early as the first decade of life. The current marketed therapy is Cystagon® (cysteamine bitartrate immediate release) which must be taken every six hours for the rest of the patient's life to prevent complications of cystinosis. Cysteamine bitartrate delayed-release capsules (RP103) is a formulation of cysteamine bitartrate that is being studied to see if it can be given less frequently, once every 12 hours, and have similar results to four times a day Cystagon®.
Read the detailed description
This is a long-term, open-label, study to determine the safety and tolerability of twice a day treatment with cysteamine bitartrate delayed-release capsules (RP103). It will involve 6-9 monthly clinic visits followed by quarterly clinic visits for the duration of the study and home use of cysteamine bitartrate delayed-release capsules.
Initially, enrollment was open to those patients who had completed the previous Phase 3 Study (RP103-03, NCT01000961). Subsequently enrollment in Study RP103-04 was opened to additional participants, including children aged 1 to 6 years and renal transplant recipients, who had previously been on a stable dose of Cystagon® for at least 21 days.
Study with completed results acquired from Horizon in 2024.
- Conditions
- Cystinosis
- Being tested
- Cysteamine Bitartrate Delayed-release Capsules
- Keywords
- cystinosis, cysteamine, inheritable disease, orphan disease, CTNS protein, human, metabolic disease, nephropathic cystinosis
- Medical subject headings
- Cystinosis, Rare Diseases, Metabolic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cysteamine Bitartrate Delayed-release CapsulesDrug
Also called RP103, PROCYSBI®
Participants who entered the trial from the RP103-03 study continued treatment with cysteamine bitartrate every 12 hours at the last dose level prescribed during their participation in that study.
Participants not entering the trial from Study RP103-03 were started on twice a day administration of cysteamine bitartrate at a total daily RP103 dose of 70% of their pre-study total daily stable Cystagon® dose.
| Study group | Role | What they receive |
|---|---|---|
| Cysteamine Bitartrate | Experimental | Cysteamine bitartrate delayed-release capsules were administered twice daily for up to 96 months. Receives: Drug: Cysteamine Bitartrate Delayed-release Capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events
Drug-related adverse events (AEs) are AEs the investigator assessed as having relation to drug of 'possibly', 'probably' or 'definitely'.
The severity of AEs was categorized according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 as follows:
- Mild (Grade 1): experience is minor and does not cause significant discomfort to subject or change in activities of daily living (ADL); subject is aware of symptoms but symptoms are easily tolerated;
- Moderate (Grade 2): experience is an inconvenience or concern to the subject and causes interference with ADL, but the subject is able to continue with ADL.
- Severe (Grade 3): experience significantly interferes with ADL and the subject is incapacitated and/or unable to continue with ADL
- Life-threatening (Grade 4): experience that, in the view of the Investigator, places the subject at immediate risk of death from the event as it occurred.
Measured: From first dose of study drug to 7 days after the last dose; median duration of treatment was 1461 days.
Secondary outcomes (2)
Trough Plasma Cysteamine Concentration
Plasma cysteamine concentration was determined using methods employing Hydrophilic Interaction Liquid Chromatography (HILC) high pressure liquid chromatography (HPLC) tandem mass spectrometry (HPLC-MS/MS).
Measured: Day 1 (predose) and Month 6, Years 1, 1.5, 2, 3, 4 and 5 at 0.5 hours post-dose
White Blood Cell Cystine Concentration
White blood cell (WBC) cystine concentration was determined using high performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS).
Measured: Day 1 (predose) and Month 6, Years 1, 1.5, 2, 3, 4 and 5 at 0.5 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2010 (estimated)
- Study start27 Aug 2010
- Primary completion26 Jun 2017
- Study completion26 Jun 2017
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 CystinosisStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 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
- NCT01197378
- Sponsor's protocol ID
- RP103-04
- Other IDs
- 2010-018365-34
- Status last verified
- Dec 2024
- First submitted
- 3 Sep 2010
- Last updated
- 27 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Dohil R, Fidler M, Barshop BA, Gangoiti J, Deutsch R, Martin M, Schneider JA. Understanding intestinal cysteamine bitartrate absorption. J Pediatr. 2006 Jun;148(6):764-9. doi: 10.1016/j.jpeds.2006.01.050.
PubMed 16769383Fidler MC, Barshop BA, Gangoiti JA, Deutsch R, Martin M, Schneider JA, Dohil R. Pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion. Br J Clin Pharmacol. 2007 Jan;63(1):36-40. doi: 10.1111/j.1365-2125.2006.02734.x.
PubMed 17229040Levtchenko EN, van Dael CM, de Graaf-Hess AC, Wilmer MJ, van den Heuvel LP, Monnens LA, Blom HJ. Strict cysteamine dose regimen is required to prevent nocturnal cystine accumulation in cystinosis. Pediatr Nephrol. 2006 Jan;21(1):110-3. doi: 10.1007/s00467-005-2052-0. Epub 2005 Oct 27.
PubMed 16252107Langman CB, Greenbaum LA, Grimm P, Sarwal M, Niaudet P, Deschenes G, Cornelissen EA, Morin D, Cochat P, Elenberg E, Hanna C, Gaillard S, Bagger MJ, Rioux P. Quality of life is improved and kidney function preserved in patients with nephropathic cystinosis treated for 2 years with delayed-release cysteamine bitartrate. J Pediatr. 2014 Sep;165(3):528-33.e1. doi: 10.1016/j.jpeds.2014.05.013. Epub 2014 Jun 16.
PubMed 24948347
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, Safety and Efficacy Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Patients With Cystinosis
- ClinicalTrials.gov ID
- NCT01197378
- Acronym / sponsor ID
- RP103-04
- Conditions
- Cystinosis
- Keywords
- cystinosis, cysteamine, inheritable disease, orphan disease, CTNS protein, human, metabolic disease, nephropathic cystinosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 27 Aug 2010 (actual)
- Primary completion
- 26 Jun 2017 (actual)
- Study completion
- 26 Jun 2017 (actual)
- First posted
- 9 Sep 2010 (estimated)
- Results
- Posted 24 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cystinosis is an inherited disease that if untreated, results in kidney failure as early as the first decade of life. The current marketed therapy is Cystagon® (cysteamine bitartrate immediate release) which must be taken every six hours for the rest of the patient's life to prevent complications of cystinosis. Cysteamine bitartrate delayed-release capsules (RP103) is a formulation of cysteamine bitartrate that is being studied to see if it can be given less frequently, once every 12 hours, and have similar results to four times a day Cystagon®.
Detailed description
This is a long-term, open-label, study to determine the safety and tolerability of twice a day treatment with cysteamine bitartrate delayed-release capsules (RP103). It will involve 6-9 monthly clinic visits followed by quarterly clinic visits for the duration of the study and home use of cysteamine bitartrate delayed-release capsules.
Initially, enrollment was open to those patients who had completed the previous Phase 3 Study (RP103-03, NCT01000961). Subsequently enrollment in Study RP103-04 was opened to additional participants, including children aged 1 to 6 years and renal transplant recipients, who had previously been on a stable dose of Cystagon® for at least 21 days.
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
| Arm | Type | Receives |
|---|---|---|
| Cysteamine Bitartrate | Experimental | Drug: Cysteamine Bitartrate Delayed-release CapsulesCysteamine bitartrate delayed-release capsules were administered twice daily for up to 96 months. |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Male and female subjects must have completed the last visit of Study RP103-03 and be willing to continue with RP103 treatment.
- Male and female subjects must have cystinosis.
- Subjects must be on a stable dose of Cystagon® at least 21 days prior to Screening.
- Within the last 6 months, no clinically significant change from normal in liver function tests (i.e., alanine aminotransferase [ALT], aspartate aminotransferase [AST], total bilirubin) and renal function (i.e., estimated glomerular filtration rate [eGFR]) at Screening as determined by the Investigator.
- Subjects with an eGFR corrected for body surface area > 30 mL/min/1.73m².
Key exclusion criteria (8 listed)
- Patients enrolled in the previous Study RP103-03 who did not complete their last scheduled Study visit or who do not wish to continue on treatment with RP103.
- Subjects less than 1 year old
- Subjects with a known history, currently of the following conditions or other health issues that make it, in the opinion of the investigator, unsafe for them to participate: inflammatory bowel disease (if currently active) or have had prior resection of small intestine; Heart disease (e.g., myocardial infarction, heart failure, unstable arrhythmias or poorly controlled hypertension) 90 days prior to Screening; Active bleeding disorder 90 days prior to Screening; Malignant disease within the last 2 years.
- Patients with a hemoglobin level < 10 g/dL at Screening or a level that, in the opinion of the investigator, makes it unsafe for the subject to participate.
- Subjects with known hypersensitivity to cysteamine or penicillamine.
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 Bitartrate Delayed-release CapsulesAlso: RP103, PROCYSBI®Participants who entered the trial from the RP103-03 study continued treatment with cysteamine bitartrate every 12 hours at the last dose level prescribed during their participation in that study. Participants not entering the trial from Study RP103-03 were started on twice a day administration of cysteamine bitartrate at a total daily RP103 dose of 70% of their pre-study total daily stable Cystagon® dose. | Drug | Cysteamine Bitartrate |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events
Time frame: From first dose of study drug to 7 days after the last dose; median duration of treatment was 1461 days.
Drug-related adverse events (AEs) are AEs the investigator assessed as having relation to drug of 'possibly', 'probably' or 'definitely'. The severity of AEs was categorized according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 as follows: * Mild (Grade 1): experience is minor and does not cause significant discomfort to subject or change in activities of daily living (ADL); subject is aware of symptoms but symptoms are easily tolerated; * Moderate (Grade 2): experience is an inconvenience or concern to the subject and causes interference with ADL, but the subject is able to continue with ADL. * Severe (Grade 3): experience significantly interferes with ADL and the subject is incapacitated and/or unable to continue with ADL * Life-threatening (Grade 4): experience that, in the view of the Investigator, places the subject at immediate risk of death from the event as it occurred.
2 secondary outcomes
Trough Plasma Cysteamine Concentration
Time frame: Day 1 (predose) and Month 6, Years 1, 1.5, 2, 3, 4 and 5 at 0.5 hours post-dose
White Blood Cell Cystine Concentration
Time frame: Day 1 (predose) and Month 6, Years 1, 1.5, 2, 3, 4 and 5 at 0.5 hours post-dose
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 16769383Dohil R, Fidler M, Barshop BA, Gangoiti J, Deutsch R, Martin M, Schneider JA. Understanding intestinal cysteamine bitartrate absorption. J Pediatr. 2006 Jun;148(6):764-9. doi: 10.1016/j.jpeds.2006.01.050.
- Background: PubMed 17229040Fidler MC, Barshop BA, Gangoiti JA, Deutsch R, Martin M, Schneider JA, Dohil R. Pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion. Br J Clin Pharmacol. 2007 Jan;63(1):36-40. doi: 10.1111/j.1365-2125.2006.02734.x.
- Background: PubMed 16252107Levtchenko EN, van Dael CM, de Graaf-Hess AC, Wilmer MJ, van den Heuvel LP, Monnens LA, Blom HJ. Strict cysteamine dose regimen is required to prevent nocturnal cystine accumulation in cystinosis. Pediatr Nephrol. 2006 Jan;21(1):110-3. doi: 10.1007/s00467-005-2052-0. Epub 2005 Oct 27.
- Derived from this study: PubMed 24948347Langman CB, Greenbaum LA, Grimm P, Sarwal M, Niaudet P, Deschenes G, Cornelissen EA, Morin D, Cochat P, Elenberg E, Hanna C, Gaillard S, Bagger MJ, Rioux P. Quality of life is improved and kidney function preserved in patients with nephropathic cystinosis treated for 2 years with delayed-release cysteamine bitartrate. J Pediatr. 2014 Sep;165(3):528-33.e1. doi: 10.1016/j.jpeds.2014.05.013. Epub 2014 Jun 16.
- RP103 (marketed as PROCYSBI) is now approved by the US FDA for management of nephropathic cystinosis in patients 6 years and older.Link provided by the sponsor.
- 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
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cysteamine Bitartrate Delayed-release Capsules in people with Cystinosis, run by Amgen at 10 sites in 3 countries.
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 9 inclusion and 8 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: finished, 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 10 sites in United States, France, Netherlands. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 24 Jul 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?
Number of Participants With Treatment-emergent Adverse Events (time frame: From first dose of study drug to 7 days after the last dose; median duration of treatment was 1461 days.). 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 NCT01197378, 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.