Withdrawal of Tiratricol Treatment in Males with Monocarboxylate Transporter 8 Deficiency (MCT8 Deficiency): A Double-blind, Randomized, Placebo-controlled Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rare Thyroid Therapeutics International AB

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

Trial duration

21 Jul 2023 → 4 Sep 2025

Decision date (initial)

2024-09-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-516124-34-00

EudraCT number

2022-001478-78

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Efficacy, Pharmacokinetic, Therapy

The primary objective is 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), as compared to continuing tiratricol treatment (tiratricol group), in males diagnosed with MCT8 deficiency and on a stable maintenance dose of tiratricol.

Secondary objectives 1

1. - To evaluate the safety and tolerability of tiratricol treatment - To evaluate the effect of tiratricol treatment upon serum thyroid hormone measurements, sex hormone binding globulin (SHBG), and cardiovascular measurements - To evaluate the serum concentrations of tiratricol

Conditions and MedDRA coding

Monocarboxylate Transporter 8 (MCT8) deficiency

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Participants will be enrolled in the present study if they meet the following eligibility 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

Exclusion criteria 1

1. Participants will be excluded from the study if they meet any of the following 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 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary endpoint 1: Rate of change from baseline in serum total T3 during the 30-day double-blind Randomized Treatment Period. Primary endpoint 2: Proportion of participants who meet the rescue criterion (serum total T3 > ULN) during the 30-day double-blind Randomized Treatment Period.

Secondary endpoints 6

1. Change in serum thyroid hormone variables (T3, T4, TSH, fT3 and fT4) from baseline to the end of Randomized Treatment Period
2. Change in serum thyroid hormone variables (T3, T4, TSH, fT3, and fT4) from screening to End of Study
3. Change in serum thyroid hormone variables (T3, T4, TSH, fT3, and fT4) from initiation of tiratricol administration at enrolment to the last measurement prior to randomization
4. Change in clinical endpoints: Heart rate (HR), systolic blood pressure (SBP) and rate pressure product (RPP) from baseline to the end of Randomized Treatment Period
5. Change in clinical endpoints: HR, SBP, RPP and body weight from screening to End of Study
6. Change in clinical endpoints: HR, SBP, RPP from initiation of tiratricol administration at screening to the last measurement prior to randomization

Investigational products

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

Test 1

Placebo 1

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 7

Locations

1 EU/EEA country · 1 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 11 files

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

Application history

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