E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011777 |
E.1.2 | Term | Cystinosis |
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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 |
Main objective The primary objective is to study the relationship between compliance of patients treated with cysteamine and the WBC cystine level.
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E.2.2 | Secondary objectives of the trial |
Secondary objectives •to study the compliance to cysteamine and its clinical impact in terms of retinal crystals and neuropsychological disorders (neurological disorders, visuoperceptual defects), •to study the relationship between compliance to cysteamine and cystine accumulation in the CNS, •to describe absorption, distribution and elimination of cysteamine, and its metabolic pathways, •to determine the concentration effect and dose effect relationship, •to compare the metabonomic network in patients with cystinosis and their controls. . |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with nephropathic cystinosis
- Male and female subjects with confirmed diagnosis of nephropathic cystinosis (defined by clinical signs and WBC cystine level). - Age > 6 years. - Subjects receiving any oral cysteamine treatment: Cystagon or RP103. - Subjects must be able to swallow their typically administered cysteamine treatment. - Sexually active female subjects of childbearing potential must agree to utilize the same acceptable form of contraception from day 1 through completion of the study. - Subjects or their parent or legal guardian must provide written informed consent prior to participation in the study. - Subjects covered by or having the right to social security.
Controls
- Age and sex matched to study population : Age range : patients aged 6 to 11 years , patients aged 12 to 17 years, adult patients: 18 or above. Sex : male or female - Subjects or their parent or legal guardian must provide written informed consent prior to participation in the study. - Subjects covered by or having the right to social security.
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E.4 | Principal exclusion criteria |
Patients with nephropathic cystinosis - Subjects receiving any form of cysteamine medication through a gastric tube. - Subjects with known hypersensitivity to cysteamine and penicillamine. - Females who are nursing, planning a pregnancy, known or suspected to be pregnant, or with a positive urinary pregnancy test. - Subjects who, in the opinion of the Investigator, are not able or willing to comply with the protocol. Contra-indication to MRI assessment
Controls for metabonomic assessment - Any uropathology or nephropathology. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint WBC cystine levels: PD measurements will be performed every month, then quarterly following usual standard of care. WBC cystine levels will be considered as a dichotomous variable (threshold = 1nmol half cystine/mg protein). Compliance under cysteamine will be measured from D1 to M24 using electronic devices (date and time of bottle opening are recorded), accountability of study treatment and information of patients’ diary. Compliance measurement between two consecutive study visits will be expressed as the proportion of the observed number of opening compared to the expected number and the cumulated dose taken compared to the expected dose. Compliance will be first considered as a dichotomous variable, the compliance being described as satisfactory if greater than 95% during a specific period. Compliance will then be considered as a quantitative variable.
Secondary endpoints - Eye examination (fundoscopy) performed every 6 month as usual standard of care. Presence or absence and accountability of crystals will be determined after centralized review of fundoscopy. - Neuropsychological disorders, visuoperceptual defects will be evaluated with specific memory and visuoperceptual tests repeated during the study (at beginning, after a year and at the end of patient’s follow-up). - NMRS assessments at M1 and M24: presence or absence of cystine accumulation, determination of the sites of cystine accumulation in the CNS and relationship with the compliance to cysteamine treatment. - Concentration of cysteamine in the CSF, associated to a measuremetn of the CSF pressure; concentration of cysteamine in urine and blood (measured by toxicological HPLC analysis with fluorescence detection); discrimination of urine and blood samples at month 1, before and after cysteamine treatment intake, from metabolic spectroscopic data obtained by nuclear magnetic resonance. - Concentration effect, dose effect model. - Perturbed metabolic network resulting from the intake of cysteamine in comparison to controls, using urine and blood samples available for patients with cystinosis and their controls.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Information not present in EudraCT |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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 | |
E.8.9.1 | In the Member State concerned months | 48 |
E.8.9.1 | In the Member State concerned days | |