Withdrawal of Tiratricol Treatment in Males With Monocarboxylate Transporter 8 Deficiency (MCT8 Deficiency)

NCT05579327 | Completed Phase 3 FDA Drug

• 1 other identifier: MCT8-2021-3
• Study Type: interventional
• Target: 20
• Locations: 3 countries
• Sites: 8

Brief Summary

This is a double-blind, randomized phase 3 multicenter placebo-controlled study in at least 16 evaluable male participants diagnosed with MCT8 deficiency. Male participants, from 4 years of age (at randomization) and having demonstrated stable maintenance treatment with tiratricol, will be randomized to receive placebo or tiratricol for 30 days or until reaching the rescue criterion (serum total triiodothyronine \[T3\] \> upper limit of normal \[ULN\] of the participant's normal range, for a sample collected during the 30-day Randomized Treatment Period). The research hypothesis to be tested is that, for participants in the placebo group, removal of tiratricol will lead to an increase of serum total T3 concentration, measured by liquid chromatography with tandem mass spectrometry (LC/MS/MS), above the ULN and requirement of rescue treatment with tiratricol, compared to those who continue to receive tiratricol.

Conditions

Monocarboxylate Transporter 8 Deficiency; Allan-Herndon-Dudley Syndrome

Keywords

MCT8; MCT8 deficiency; Allan-Herndon-Dudley syndrome; Tiratricol; Triac

Outcome Measures

Primary Outcomes (2)

• Rate of change from baseline in serum total T3 (ln-transformed) during the 30-day double-blind Randomized Treatment Period

  Baseline to Day 30

• Proportion of participants who meet the rescue criterion (serum total T3 > ULN) during the 30-day double-blind Randomized Treatment Period

  Baseline to Day 30

Secondary Outcomes (11)

• Change in serum thyroid hormone variables (T3, T4, TSH, fT3, and fT4)

  From i) Baseline to Day 30, ii) Screening to End of Study (up to 26 weeks), iii) first tiratricol administration in Run-in/Dose Titration Period to last measurement prior to randomization (up to 16 weeks)

• Change in clinical endpoints: Heart rate

  From i) Baseline to Day 30, ii) Screening to End of Study (up to 26 weeks), iii) first tiratricol administration in Run-in/Dose Titration Period to last measurement prior to randomization (up to 16 weeks)

• Change in clinical endpoints: Systolic blood pressure

  From i) Baseline to Day 30, ii) Screening to End of Study (up to 26 weeks), iii) first tiratricol administration in Run-in/Dose Titration Period to last measurement prior to randomization (up to 16 weeks)

• Change in clinical endpoints: Rate pressure product (heart rate × systolic blood pressure)

  From i) Baseline to Day 30, ii) Screening to End of Study (up to 26 weeks), iii) first tiratricol administration in Run-in/Dose Titration Period to last measurement prior to randomization (up to 16 weeks)

• Change in clinical endpoints: Heart rate Z scores

  From i) Baseline to Day 30, ii) Screening to End of Study (up to 26 weeks), iii) first tiratricol administration in Run-in/Dose Titration Period to last measurement prior to randomization (up to 16 weeks)

Study Arms (2)

Tiratricol

EXPERIMENTAL

Drug: Tiratricol

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Tiratricol DRUG

Tiratricol tablets are flat tablets that contain 350 µg tiratricol. Treatment will be administered orally or via percutaneous endoscopic gastrostomy (PEG) tube; tablets will be suspended in water and, if needed, mixed with mashed food for oral administration or administered in water through the PEG tube as applicable.

Tiratricol

Placebo DRUG

Placebo tablets will be identical in appearance to tiratricol tablets but contain no tiratricol. Treatment will be administered orally or via PEG tube; tablets will be suspended in water and, if needed, mixed with mashed food for oral administration or administered in water through the PEG tube as applicable. During the Randomized Treatment Period, participants will receive the same number of tablets as the stable dose of open-label tiratricol they were receiving before randomization.

Placebo

Eligibility Criteria

• Age: 4 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male participants diagnosed with a pathogenic mutation in the MCT8 gene, confirmed with a genetic test.
• Serum total T3 concentration above the ULN of the age specific normal range:
• 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)
• in the Screening Visit sample:
• i. For participants who have never received and/or are currently not receiving tiratricol.
• 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.
• Signed and dated informed consent form from the parents or legal guardian.

You may not qualify if:

• 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.
• Body weight \<10 kg at the Screening Visit.
• Patients who are participating, or intend to participate, in other therapeutic and/or interventional clinical studies during the study period.
• History of allergic reactions to components of tiratricol or any excipients in the investigational product (IP).
• Participants with any contra-indication for treatment with tiratricol or any excipients in the IP.
• Participants who have used other T3 analogues, levothyroxine, propylthiouracil, or other antithyroid medications within 6 weeks of screening.
• Randomization Criteria:
• In addition to the eligibility criteria, participants must meet further criteria at the time of randomization to enter the Randomized Treatment Period.
• Confirmation that the "Stable Dose Criterion" has been met.
• Confirmation that participant is at least 4 years of age at the time of randomization.

Sponsors & Collaborators

• Premier Research: collaborator
• Egetis Therapeutics: collaborator
• Rare Thyroid Therapeutics International AB: lead

Study Sites (8)

Rare Disease Research, LLC

Kissimmee, Florida, 34746, United States

Location

Rare Disease Research, LLC

Atlanta, Georgia, 30329, United States

Location

SSM Health Cardinal Glennon Children's Hospital

St Louis, Missouri, 63104, United States

Location

Rare Disease Research, LLC

Hillsborough, North Carolina, 27278, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Tranquil Clinical and Research Consulting Services

Webster, Texas, 77598, United States

Location

Erasmus MC

Rotterdam, 3015 GD, Netherlands

Location

Addenbrooke's Hospital

Cambridge, United Kingdom

Location

MeSH Terms

Conditions

Allan-Herndon-Dudley syndrome

Interventions

3,3',5-triiodothyroacetic acid

Study Officials

• Andrew J. Bauer, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

• W. E. Visser, MD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: Patients having demonstrated stable maintenance treatment with tiratricol will be randomized to receive placebo or tiratricol for 30 days or until reaching rescue criterion (serum total T3 \> ULN of the participant's normal range, for a sample collected during the 30-day Randomized Treatment Period). In other words, the patients will be randomized to complete withdrawal of tiratricol treatment (placebo) for 30 days or to continue with the stable tiratricol maintenance treatment for 30 days. If, during the 30 days, a rescue criterion (serum total T3 \> ULN of the participant's normal range) is reached, the randomized treatment will be stopped, and the patient will go back on unblinded tiratricol treatment. Serum total T3 concentrations measured during the Randomized Treatment Period that are below the LLN of the normal range will not lead to any modifications to the blinded study drug administration schedule of daily tiratricol dosing.

Study Record Dates

• First Submitted: September 29, 2022
• First Posted: October 13, 2022
• Study Start: July 21, 2023
• Primary Completion: July 22, 2025
• Study Completion: September 3, 2025
• Last Updated: April 8, 2026

Record last verified: 2026-04

Locations

US (6); NL (1); GB (1)