Stopping Tiratricol Treatment in Males with MCT8 Deficiency

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

This study is testing if stopping tiratricol treatment affects hormone levels in boys and men with MCT8 deficiency compared to those who keep taking the medication.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 4 Years and up
• Sex: Male
• Sponsor: Rare Thyroid Therapeutics International AB (Industry-sponsored)
• Locations: 8 sites (Kissimmee, Florida and 7 other locations)
• Trial ID: NCT05579327 on ClinicalTrials.gov

What this trial studies

This phase 3 clinical trial is a double-blind, randomized, multicenter study involving male participants diagnosed with MCT8 deficiency. Participants, aged 4 years and older, will be randomly assigned to receive either tiratricol or a placebo for 30 days after establishing a stable maintenance dose of tiratricol. The study aims to determine if stopping tiratricol leads to an increase in serum total T3 concentration in the placebo group compared to those who continue treatment. The trial includes a screening period to ensure participants meet the stable dose criterion before randomization.

Who should consider this trial

Good fit: Ideal candidates are male participants aged 4 years and older with a confirmed pathogenic mutation in the MCT8 gene and elevated serum total T3 levels.

Not a fit: Patients with major illnesses or recent major surgeries unrelated to MCT8 deficiency may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide insights into the management of MCT8 deficiency and improve treatment protocols for affected patients.

How similar studies have performed: While there have been studies on MCT8 deficiency, this specific approach of withdrawing tiratricol treatment is novel and has not been extensively tested.

Eligibility criteria

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:

   1. 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
   2. in the Screening Visit sample, or most recent standard of care sample prior to screening, for participants who have never received and/or currently not receiving tiratricol.
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. 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 using other T3 analogues, levothyroxine, or propylthiouracil.

Randomization Criteria:

In addition to the eligibility criteria, participants must meet further criteria at the time of randomization to enter the Randomized Treatment Period.

1. Confirmation that the "Stable Dose Criterion" has been met.
2. Absence of any new or exacerbated medical or surgical condition that fulfils Exclusion criterion #1.
3. Confirmation that participant is at least 4 years of age at the time of randomization.

Where this trial is running

Kissimmee, Florida and 7 other locations

• Rare Disease Research, LLC — Kissimmee, Florida, United States (Recruiting)
• Rare Disease Research, LLC — Atlanta, Georgia, United States (Recruiting)
• SSM Health Cardinal Glennon Children's Hospital — Saint Louis, Missouri, United States (Withdrawn)
• Rare Disease Research, LLC — Hillsborough, North Carolina, United States (Recruiting)
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Recruiting)
• Tranquil Clinical and Research Consulting Services — Webster, Texas, United States (Recruiting)
• Erasmus MC — Rotterdam, Netherlands (Recruiting)
• Addenbrooke's Hospital — Cambridge, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Andrew J. Bauer, MD — Children's Hospital of Philadelphia
• Study coordinator: Kristina Sjoblom Nygren

Conditions Monocarboxylate Transporter 8 Deficiency; Allan-Herndon-Dudley Syndrome; MCT8; MCT8 deficiency; Allan-Herndon-Dudley syndrome; Tiratricol; Triac