Tiratricol treatment of children with Monocarboxylate Transporter 8 deficiency: Triac Trial II

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rare Thyroid Therapeutics International AB

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

Trial duration

3 Feb 2021 → ongoing

Decision date (initial)

2024-08-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Eurostars-2 Joint Programme

External identifiers

EU CT number

2024-516123-13-00

EudraCT number

2019-003370-35

ClinicalTrials.gov

NCT02396459

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Therapy

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.

Secondary objectives 1

1. 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).

Conditions and MedDRA coding

Monocarboxylate Transporter 8 (MCT8) deficiency

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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.

Exclusion criteria 1

1. 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 *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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Part I of the study: GMFM-88 total score and BSID-III 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.

Secondary endpoints 1

1. Part I and II:GMFM-88 individual item score 10 ("lifts head upright") and item score 24 ("sit on mat") at week 96, at 3 and 4 years respectively, compared to baseline; GMFM Domain B (Sitting) - summary score of all items 18-37 at week 96, at 3 and 4 years respectively, compared to baseline; Motor milestone responder analysis of Section 2 of the Hammersmith Infant Neurological Examination (HINE) at week 96, at 3 and 4 years respectively.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rare Thyroid Therapeutics International AB

Sponsor organisation

Rare Thyroid Therapeutics International AB

Address

Klara Norra Kyrkogata 26, Stockholms Domkyrkofors Stockholms Domkyrkofors

City

Stockholm

Postcode

111 22

Country

Sweden

Scientific contact point

Organisation

Rare Thyroid Therapeutics International AB

Contact name

Clinical Trials

Public contact point

Organisation

Rare Thyroid Therapeutics International AB

Contact name

Clinical Trials

Third parties 4

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 46 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications