| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10011777 |
| E.1.2 | Term | Cystinosis |
| E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Primary Objective:
• To assess safety and tolerability of long-term repeat dosing of RP103 in patients with nephropathic cystinosis. |
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| E.2.2 | Secondary objectives of the trial |
Secondary Objectives:
• To assess the steady-state pharmacokinetics (PK) and pharmacodynamics (PD) of RP103.
• To assess the long term quality of life using either PedsQL™ or SF-36® instruments. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Optional PK Substudy Visit for Subjects 6 Years Old or Younger:
The optional PK Substudy Visit may take place during a regularly scheduled RP103-04 Quarterly Visit, or it may take place as a separately scheduled visit. PK samples will be collected within 15 minutes pre- and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-RP103 morning dose. PD samples will be collected at 0.5 and 3 hours post-RP103 morning dose. During the PK Substudy Visit, blood samples will be collected at the following timepoints:
PK Blood Samples:
Time 0 (within 15 minutes prior to the morning RP103 dose)
0.5 hour (30 minutes) post-dose
1 hour post-dose
2 hours post-dose
3 hours post-dose
4 hours post-dose
6 hours post-dose
8 hours post-dose
10 hours post-dose
12 hours post-dose (within 15 minutes prior to the evening RP103 dose)
PD Blood Sample:
0.5 hour (30 minutes) after the morning RP103 dose
3 hours post-dose |
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| E.3 | Principal inclusion criteria |
1. 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:
2. Male and female subject with a documented diagnosis of cystinosis.
3. Subject must be on a stable dose of Cystagon® at least 21 days prior to Screening.
4. Within the last 6 months, no clinically significant change from normal in liver function tests [i.e., 1.5 times ULN for ALT and AST, and/or 1.5 times ULN for total bilirubin] and renal function [i.e., estimated GFR (corrected for body surface area)] at Screening as determined by the Investigator.
5. Subject must have an estimated GFR (corrected for body surface area) > 30 mL/minute/1.73 m2.
6. 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. The acceptable forms of contraception for this Study include hormonal contraceptives (oral, implant, transdermal patch, or injection) at a stable dose for at least 3 months prior to Screening, barrier (spermicidal condom, diaphragm with spermicide), IUD, or a partner who has been vasectomized for at least 6 months. For pre-pubescent children, a documented attestation of abstinence from their parent or guardian will be acceptable.
7. Subject must be willing and able to comply with the Study restrictions and requirements.
8. Subject or their parent or guardian must provide written informed consent and assent (where applicable) prior to participation in the Study. |
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| E.4 | Principal exclusion criteria |
1. 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:
2. Subjects less than 1 year old
3. Subjects with current history of the following conditions or any other health issues that make it, in the opinion of the Investigator, unsafe for them to participate:
• Inflammatory bowel disease (if currently active) or 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;
• History of malignant disease within the last 2 years.
4. Subject with a hemoglobin level of < 10 g/dL at Screening or, in the opinion of the Investigator, a hemoglobin level that would make it unsafe for the subject to participate.
5. Subjects with known hypersensitivity to cysteamine and penicillamine.
6. Female subjects who are nursing, planning a pregnancy, known or suspected to be pregnant, or with a positive serum pregnancy screen.
7. Subjects who, in the opinion of the Investigator, are not able or willing to comply with the protocol. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Safety Endpoints:
• The safety profile of RP103 will be investigated by safety reviews conducted by the Investigator at or prior to each Monthly or Quarterly visit and through adverse event report monitoring (including attribution of treatment-emergent adverse events and serious adverse events [SAEs]), physical examination (including basic neurological and skin assessment findings), vital signs, ECG and clinical laboratory testing as outlined in the Schedule of Events.
Pharmacokinetic Endpoint:
• The trough plasma cysteamine concentration will be measured from samples collected 0.5 hour post dose at each Study visit.
Pharmacodynamic Endpoint:
•The WBC cystine content will be measured from samples collected 0.5 hour post dose at each Study visit.
Exploratory Endpoints:
• The longitudinal change in the use of concomitant gastric acid reduction therapies, VAS swallowing difficulty and PedsQL™ or SF-36® questionnaire scores while being administered RP103. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Monthly Study Visits are only for patients who completed Study RP103-03 and will begin within 1 month (± 7 days) after study entry. Each patient will complete a minimum of 6 consecutive Monthly visits.
Quarterly Study Visits will commence for each patient ≥ 1 month and < 4 months after the patient has completed at least 6 consecutive Monthly visits.
Each Quarterly visit will take place by the middle of the first month (± 7 days) of each calendar quarter (i.e., January 15, April 15, July 15 and October 15).
Depending on enrollment timing, up to 6 Quarterly visits may occur over this 3 year study |
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| E.5.2 | Secondary end point(s) |
To assess the steady-state pharmacokinetics (PK) and pharmacodynamics(PD) of RP103.
To assess the long term quality of life using either PedsQL™ or SF-36® instruments. |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Monthly Study Visits are only for patients who completed Study RP103-03 and will begin within 1 month (± 7 days) after study entry. Each patient will complete a minimum of 6 consecutive Monthly visits.
Quarterly Study Visits will commence for each patient ≥ 1 month and < 4 months after the patient has completed at least 6 consecutive Monthly visits.
Each Quarterly visit will take place by the middle of the first month (± 7 days) of each calendar quarter (i.e., January 15, April 15, July 15 and October 15).
Depending on enrollment timing, up to 6 Quarterly visits may occur over this 3 year study |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 5 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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