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 |
Part I: Evaluate the effects of tiratricol treatment on neurodevelopment in young MCT8 deficiency patients, as measured by the Gross Motor Function Measure (GMFM-88) and Bayley Scales of Infant Development (BSID)-III Gross Motor Skill Domain.
Part II: Evaluate the effects of long-term treatment (up to 4 years of total treatment) with tiratricol on neurodevelopment in young boys (≤30 months) with MCT8 deficiency, as measured by the Gross Motor Function Measure (GMFM)-88 and Bayley Scales of Infant Development (BSID)-III Gross Motor Skill Domain. |
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E.2.2 | Secondary objectives of the trial |
Part I: 1. Evaluate the effect of Tiratricol treatment at week 96 on specific motor development milestones. 2. Evaluate the effect of tiratricol treatment on neurodevelopment in young MCT8 deficient patients as measured by the BSID-III. 3. Evaluate the effect of tiratricol at week 96 on clinical and biochemical thyrotoxic features (serum T3 concentrations, tissue specific markers of thyroid hormone action).
Part II: 1. Evaluate the effect of long-term treatment (up to 4 years of total treatment) with tiratricol on specific motor development milestones. 2. Evaluate the effect of long-term treatment (up to 4 years of total treatment) with tiratricol as measured by the BSID-III. 3. Evaluate the long-term treatment effect (up to 4 years of total treatment) 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 be male and 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 LT4 and/or PTU and/or other anti-thyroid medication for a period longer than three months. Patients previously treated with LT4 for a shorter period than 3 months may be included in the study (baseline visit) six weeks (or longer) after last dose of LT4 if two consecutive analyses show stable TFT*. Patients treated with PTU and/or other anti-thyroid medication for a shorter period than three months may be included in the study (baseline visit) six weeks (or longer) after last dose. 3. Major illness or recent major surgery (within four weeks of baseline visit 1) unrelated to MCT8 deficiency. 4. Known allergic reactions to components of the IMP. Patients with galactose intolerance, Lapp lactase deficiency or malabsorption of glucose or galactose (the IMP contains lactose). 5. Treatment with another investigational drug or participation in other interventional trial within three months prior to baseline visit 1.
*Stable TFT (T3, T4, fT4), determined as a maximal variation of 20%, should be demonstrated at two separate occasions at least two weeks apart, measured on the same platform.
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E.5 End points |
E.5.1 | Primary end point(s) |
Part I of the study: GMFM-88 total score and BSID Gross Motor Skill Domain at week 96 compared to natural history scores from the Triac Trial I study Part II of the study: GMFM-88 total score and BSID-III Gross Motor Skill Domain at 3 years and 4 years respectively, compared to natural history scores from the Triac Trial I study.* |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part I: At week 96 compared to historical controls Part II: After 4 years compared to historical controls |
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E.5.2 | Secondary end point(s) |
Part I: 1. GMFM-88 individual item score 10 (“lifts head upright”) and item score 24 (“sit on mat”) at week 96 compared to baseline; GMFM Domain B (Sitting) - summary score of all items 18-37 at week 96 compared to baseline; Motor milestone responder analysis of Section 2 of the Hammersmith Infant Neurological Examination (HINE) at week 96. 2. Age equivalent (AE) score from the BSID-III compared to baseline and historical controls. 3. Serum T3 (efficacy), peripheral thyroid hormone status (serum SHBG; serum creatine kinase, creatinine, blood pressure and body weight) (efficacy).
Part II: 1. GMFM-88 individual item score 10 (“lifts head upright”) and item score 24 (“sit on mat”) at 3 years and 4 years respectively, compared to baseline in Triac Trial II; GMFM Domain B (Sitting) - summary score of all items 18-37 at 3 years and 4 years respectively, compared to baseline in Triac Trial II; Motor milestone responder analysis of Section 2 of the Hammersmith Infant Neurological Examination (HINE) at 3 years and 4 years respectively. 2. Age equivalent (AE) score from the BSID-III at 3 years and 4 years respectively, compared to baseline and historical controls. 3. Serum T3 (efficacy) at 3 years and 4 years respectively, peripheral thyroid hormone 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 |
Part I: At week 96 compared to historical controls Part II: After 4 years compared to historical controls |
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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
| 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 | 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 |
United States |
Netherlands |
Czechia |
Germany |
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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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The end of the study is defined as completion of the last visit for the last patient in the trial globally. The end of Part I is defined as last patient completing visit 13. Patients who completed Part I of the study will be offered to continue treatment for another 112 weeks in Part II. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |