|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|Diseases [C] - Nutritional and Metabolic Diseases [C18]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|10010331 - Congenital, familial and genetic disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To demonstrate superiority of RP103 versus Cystagon® in controlling white blood cell cystine (WBC) levels over 24 hours in patients with cystinosis and to assess long-term safety and tolerability of RP103
|Secondary objectives of the trial
|To compare WBC cystine measurements provided by a central
laboratory versus sites’ local (regional, not associated with the
clinical trial) laboratories.
To assess long-term quality of life and sleep using instruments
appropriate to the subjects’ age and region (US or Europe).
To assess subject dosing compliance with two different
cysteamine bitartrate formulations, Q6H immediate-release
Cystagon® versus Q12H delayed-release RP103.
To assess halitosis during Cystagon® and RP103 treatment in a
subgroup of subjects
|Trial contains a sub-study
|Full title, date and version of each sub-study and their related objectives
|Some cystinosis patients have bad breath (halitosis) when they take
Cystagon. "Halitosis Substudy" is an optional portion of the study
protocol, that will investigate the concentration of dimethylsulfide (DMS)
in expired air – breath samples – after the administration of study
medication and measuring PK samples at two visits: Substudy Visit 1
while taking Cystagon and Substudy Visit 2 while taking RP103. The
substudy visits occur at the same time as regularly scheduled study
|Principal inclusion criteria
|1. Male or female with a documented diagnosis of cystinosis.
2. On a stable dose of Cystagon® for at least 21 days prior to Screening.
3. WBC cystine level > 1 nmol ½ cystine/mg of protein on average over
at least 2 measurements collected during the 2 years prior to Screening.
4. No clinically significant change in liver function tests, i.e. 1.5 times
ULN for ALT and AST, and/or 1.5 times ULN for total bilirubin, within 6
months prior to Screening.
5. No clinically significant change in renal function, i.e. estimated GFR
within 6 months prior to Screening.
6. Must have an estimated GFR > 20 mL/minute/1.73 m2 (using the
equation from Schwartz 2009 J Am Soc Nephrol 20:629-637) 1.
7. Female subjects who are sexually active and of childbearing potential,
i.e. not surgically sterile (tubal ligation, bilateral oopherectomy, or
hysterectomy) or at least 2 years naturally postmenopausal must agree
to use an acceptable form of contraception from Screening through
completion of the study. 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 or diaphragm with spermicide), IUD, or a
partner who has been vasectomized for at least 6 months.
8. Subject or their parent or guardian must provide written informed
consent and assent (where applicable) prior to participation in the study.
|Principal exclusion criteria
|1. Younger than 12 years of age.
2. Current history of the following conditions or any other
health issues that make it, in the opinion of the Investigator,
unsafe for study participation:
- 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) within 90 days prior to Screening;
-Active bleeding disorder within 90 days prior to
- History of malignant disease within 2 years prior to
3. Hemoglobin level of < 9 g/dL at Screening or, in the opinion
of the Investigator, a hemoglobin level that would make it
unsafe for study participation.
4. Known hypersensitivity to cysteamine and penicillamine.
5. Female subjects who are nursing, planning a pregnancy, or
are known or suspected to be pregnant.
6. Subjects who, in the opinion of the Investigator, are not able or willing to comply with study requirements.
|E.5 End points
|Primary end point(s)
|Comparison of steady-state cysteamine-trough WBC cystine
levels between Cystagon® and RP103 over 3 months for each
|Timepoint(s) of evaluation of this end point
|Months 1,2 and 3 vs Months 5,6 and 7
(Comparing the Cystagon and RP103 3-month treatment periods)
|Secondary end point(s)
The safety profile of RP103 will be investigated by changes
from the last study visit as noted in the following safety
assessments: physical examination, vital signs, ECG and
clinical laboratory testing. Incidence of adverse event report
(including attribution of treatment-emergent non-serious and
serious adverse events) will be recorded.
Halitosis Substudy participants only: Cmax, Tmax and AUCs
for plasma cysteamine and expired air DMS concentrations
will be determined.
The WBC cystine content will be measured from samples
collected within 15 minutes pre-dose under Cystagon® or 30
minutes post-dose under RP103 at each study visit.
Central laboratory versus local laboratory WBC cystine
The longitudinal change in the use of concomitant gastric
acid reduction therapies, quality of life questionnaires, and VAS swallowing difficulty and sleep rating scale scores.
|Timepoint(s) of evaluation of this end point
|Safety and secondary endpoints will be assesed following every pertinent study visit. Unless they discontinue the study, subjects will complete Screening, Day 1, an 8 bi-Monthly (every 2 week) visits, i.e. through Month 7 plus Termination Visit. If study drug is not yet approved , that will be followed by Quarterly visits, up to 24 Months.
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|last visit of last subject undergoing the trial.
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days