|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|Genetic form of diabetes, blindness and neuroegneration
|Diseases [C] - Nervous System Diseases [C10]
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|The Primary objective is:
To determine the effectiveness of Sodium Valproate treatment in delaying the loss of vision in Wolfram syndrome
|Secondary objectives of the trial
|There is one secondary research objective. This is:
To assess the safety and tolerability of sodium valproate treatment, given as tablets by mouth over the 36 months of the Trial.
|Trial contains a sub-study
|Principal inclusion criteria
|Patients must meet all of the following criteria to be eligible for enrolment:
1. The patient is aged 5 years or older and has a definitive diagnosis of Wolfram syndrome, as determined by the following:
a. Documented diabetes mellitus diagnosed under 16 completed years according to WHO or ADA criteria plus documented optic atrophy diagnosed under 16 completed years AND
b. Documented functionally relevant mutations on one or both alleles of the WFS1 gene based on historical test results (if available) or from a qualified laboratory at screening.
2. The patient’s visual acuity, assessed as the mean of right eye and left eye corrected visual acuities assessed separately has a LogMAR score of 1.6 or better on an EDTRS chart.
3. The patient, patient’s parent(s), or legally authorized guardian(s) must have voluntarily signed an Institutional Review Board/Independent Ethics Committee-approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient. The guardians’ consent and patient’s assent, if relevant, must be obtained.
4. Women of child bearing potential will only be included after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test. If sexually active, they must agree to use a highly effective contraception measure, with additional pregnancy testing at monthly intervals.
5. Sexually active men with a female partner of childbearing potential must agree to the use of condoms and the use of a highly effective method of contraception by the female partner
6. Patient willing and able to meet all protocol defined visits for the duration of the Trial
|Principal exclusion criteria
|Patients who meet any of the following criteria are not eligible for this study:
1. The patient has clinically significant non-Wolfram related Central Nervous System (CNS) involvement, which is judged by the Investigator to be likely to interfere with the accurate administration and interpretation of protocol assessments.
2. The patient has a diagnosis of a mitochondrial myopathy
3. The patient has active liver disease, has a personal or family history of liver dysfunction, or has porphyria.
4. The patient has a mutation in the POLG gene that is known to be associated with sodium valproate induced liver injury
5. The patient has received treatment with any investigational drug within the 30 days prior to study entry.
6. The patient is currently taking sodium valproate; or has a known hypersensitivity to sodium valproate or its excipients.
7. Any other acute or chronic medical, psychiatric, social situation or laboratory result that, based on investigator’s judgment, would jeopardize patient safety during trial participation, cause inability to comply with the protocol, or affect the study outcome.
8. The Patient is currently breastfeeding
9. The Patient has Known urea cycle disorders
10. The patient has one of the following disorders; Lactose intolerance, the Lapp lactase deficiency, or glucose- galactose malabsorption
|E.5 End points
|Primary end point(s)
|a) Rate of change in visual acuity (EDTRS chart)
|Timepoint(s) of evaluation of this end point
|Planned interim analysis after 24 months of intervention and placebo.
Planned final analysis within 6 months of the final assessment of the final patient.
|Secondary end point(s)
|Safety of sodium valproate administration
|Timepoint(s) of evaluation of this end point
|We will assess the safety of sodium valproate by comparing the proportion of patients who experience an adverse event of specific interest in the first 3 months of treatment.
SAE's will be monitored and evaluated throughout the trial.
|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
|Number of sites anticipated in 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
|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
|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