E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Monocarboxylate Transporter 8 (MCT8) deficiency |
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E.1.1.1 | Medical condition in easily understood language |
MCT 8 deficiency or AHDS (Allan-Herndon-Dudley syndrome) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
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 |
To evaluate the effects of tiratricol treatment on neurodevelopment in young MCT8 deficiency patients as measured by the Gross Motor Function Measure 88 (GMFM-88). |
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E.2.2 | Secondary objectives of the trial |
1) To evaluate the effect of tiratricol treatment on specific Motor Development milestones by individual item scores in the Gross Motor Function Measure test.
2) To evaluate the effect of tiratricol treatment on neurodevelopment in young MCT8 deficient patients as measured by the Bayley Scales of Infant Development (BSID-III).
3) Evaluate the effect of tiratricol on clinical and biochemical thyrotoxic features (serum T3 concentrations, tissue specific markers of thyroid hormone action). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated informed consent form from the parents or legal guardian.
2. Parents stated willingness to comply with all study procedures and availability for the duration of the study.
3. The participant should be aged between 0 and 30 months on the day of inclusion.
4. The participant should have a pathogenic mutation in the MCT8 gene.
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E.4 | Principal exclusion criteria |
1. Previous treatment with tiratricol.
2. Previous treatment with a combination of Propylthiouracil (PTU) and Levothyroxine (LT4).
3. Previous treatment with LT4 for a longer period than three months.
4. Treatment with LT4 within three months of baseline visit.
5. Major illness or recent major surgery (within four weeks of baseline visit 1) unrelated to MCT8 deficiency.
6. Known allergic reactions to components of the IMP.
7. Treatment with another investigational drug or participation in other interventional trial within three months prior to baseline visit 1.
8. Patients that have any contra-indication for tiratricol treatment as stated in the Investigators Brochure.
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E.5 End points |
E.5.1 | Primary end point(s) |
GMFM-88 score compared to natural history GMFM-88 scores from untreated patients. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 24 months of treatment compared to baseline. An interim analysis will be done after 12 months treatment. |
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E.5.2 | Secondary end point(s) |
1) Gross Motor Function Measure test (GMFM-88) individual item score 10 and 24 compared to natural history scores from untreated patients.
2) Age equivalent (AE) score from the BSID compared to natural history AE scores from untreated patients.
3) Serum T3 (efficacy), peripheral thyroid hormone TH status (serum SHBG; serum creatine kinase, creatinine, blood pressure and body weight) (efficacy).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 24 months of treatment compared to baseline. An interim analysis will be done after 12 months treatment. |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | 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 | 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) | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 | No |
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 |
Czech Republic |
France |
Germany |
Italy |
Netherlands |
United Kingdom |
United States |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |