Withdrawal of Tiratricol treatment of children with Monocarboxylate Transporter 8 deficiency: ReTRIACt

Phase 1

• Conditions: Monocarboxylate Transporter 8 (MCT8) deficiency; Therapeutic area: Diseases [C] - Hormonal diseases [C19]

• Registration Number: EUCTR2022-001478-78-NL
• Lead Sponsor: Rare Thyroid Therapeutics International AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-10-25
• Last Update Posted: 15 July 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Male
• Target Recruitment: 16

Inclusion Criteria

1.Male participants diagnosed with a pathogenic mutation in the MCT8 gene, confirmed with a genetic test.
2.Serum total T3 concentration above the ULN of the age specific normal range :
a)at the time of diagnosis (or the closest sample taken prior to first ever treatment with tiratricol) for participants who are currently treated with tiratricol (if serum total T3 concentration is not available, free T3 results from standard of care samples may be used).
b)In the Screening Visit sample:
i.For participants who have never received and/or are currently not receiving tiratricol.
ii.For participants who stopped prohibited medications per exclusion criterion #6
3.Participants will be aged 4 years or older at the time of randomization.
Participants entering screening who are <4 years of age but expected to be aged 4 years at randomization should be discussed with the medical monitor.
4.Signed and dated informed consent form from the parents or legal guardian.

Are the trial subjects under 18? yes
Number of subjects for this age range: 16
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 3
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Major illness or recent major surgery unrelated to MCT8 deficiency (in the principal investigator’s judgement), defined as:
•Conditions requiring repeated hospitalizations that are likely to confound ability to participate in the trial.
•Major illness in the 3 months prior to the Screening Visit that is likely to confound the ability of the participant to participate fully within the trial and/or confound the assessment of serum total T3 and/or safety.
•Major surgery within the 3 months prior to the Screening Visit or planned to take place during the study, including but not limited to major abdominal/thoracic/neurosurgical procedures.
•Major/minor abdominal and/or maxillofacial surgery that may inhibit the administration and/or absorption of study drug.
2.Body weight <10 kg at the Screening Visit.
3.Patients who are participating, or intend to participate, in other therapeutic and/or interventional clinical studies during the study period.
4.History of allergic reactions to components of tiratricol or any excipients in the investigational product (IP).
5.Participants with any contra-indication for treatment with tiratricol or any excipients in the IP.
6.Participants who have used other T3 analogues, levothyroxine, propylthiouracil, or other antithyroid medications within 6 weeks of screening

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the effects of withdrawal of tiratricol treatment (placebo group) on serum total triiodothyronine (T3) concentrations, measured by liquid chromatography with tandem mass spectrometry (LC/MS/MS), and the requirement for rescue treatment with tiratricol as compared to continuing tiratricol treatment (tiratricol group), in males diagnosed with MCT8 deficiency and on a stable maintenance dose of tiratricol;Secondary Objective: 1. To evaluate the safety and tolerability of tiratricol treatment<br>2. To evaluate the effect of tiratricol treatment upon serum thyroid hormone measurements, sex hormone binding globulin (SHBG), and cardiovascular measurements<br>3. To evaluate the serum concentrations of tiratricol<br><br>;Primary end point(s): Proportion of participants who meet the rescue criterion (serum total T3 > ULN) from samples obtained during the 30 day double-blind Randomized Treatment Period;Timepoint(s) of evaluation of this end point: end of Randomized Treatment period