Safety and Efficacy of Tideglusib in Congenital or Childhood Onset Myotonic Dystrophy

Официальное название

An Open-Label Study to Evaluate the Long-Term Safety and Efficacy of Tideglusib for the Treatment of Congenital or Childhood Onset DM1 (REACH CDM X)

Обзор

This is an open-label phase 2/3 study for individuals with Congenital Myotonic Dystrophy (Congenital DM1) who participated in the preceding AMO-02-MD-2-003 study or individuals with either Congenital or Childhood Onset DM1 who are treatment naïve.

Подробное описание

This is an open-label study of either a weight-adjusted 1000 mg fixed dose or a weight banded fixed dose of tideglusib across a 52-week treatment period with an open-ended optional extended access period. The subjects are children and adolescents with Congenital DM1 who participated in the antecedent AMO-02-MD-2-003 study or individuals with either Congenital or Childhood onset DM1 who are treatment naïve.

Вмешательства

• Препарат Tideglusib
  Tideglusib dosing will be weight-adjusted at 400 mg, 600 mg, or 1000 mg dose levels, or weight banded fixed doses of 400 mg, 600 mg, 800 mg or 1000 mg, with each subject starting at a weight-adjusted 400 mg dose level for 2 weeks, then up titrating to a weight-adjusted 600 mg dose level for the next 2 weeks.

Первичные конечные точки

• Safety (Adverse Events) [Срок оценки: 52 Weeks]
• Safety (Adverse Events) - With Optional Expanded Access [Срок оценки: Week 60 and every 8 weeks thereafter up until discontinuation or study closure, assessed up to Week 132]
• Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS) [Срок оценки: 52 Weeks]

Вторичные конечные точки (12)

• Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS) - With Optional Expanded Access [Срок оценки: Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132]
• Clinical Global Impressions Improvement Scale (CGI-I) [Срок оценки: 54 Weeks]
• Clinical Global Impressions Improvement Scale (CGI-I) - With Optional Expanded Access [Срок оценки: Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132]
• Top 3 Caregiver Concerns Visual Analogue Scale (VAS) score [Срок оценки: 54 weeks]
• Top 3 Caregiver Concerns Visual Analogue Scale (VAS) score - With Optional Expanded Access [Срок оценки: Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132]
• Caregiver Completed Congenital DM1 Rating Scale (CC-CDM1-RS) [Срок оценки: 52 weeks]
• Caregiver Completed Congenital DM1 Rating Scale (CC-CDM1-RS) - With Optional Expanded Access [Срок оценки: Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132]
• Clinical Global Impressions Severity Scale (CGI-S) [Срок оценки: 54 weeks]
• Clinical Global Impressions Severity Scale (CGI-S) - With Optional Expanded Access [Срок оценки: Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132]
• Autism Behavior Inventory- Clinician (ABI-C) [Срок оценки: 52 Weeks]
• Socialization, Communication, Daily Living, and Adaptive Behavior Composite standard scores of the Vineland Adaptive Behavior Scale - Survey Interview [Срок оценки: 52 Weeks]
• 10-meter walk-run test [Срок оценки: 52 Weeks]

Критерии участия

Критерии включения

Subjects who do not enter this study directly from completing the AMO-02-MD-2-003 study (i.e. subjects who did not complete AMO-02-MD-2-003, subjects who completed AMO-02-MD-2-003 but did not directly rollover or subjects who are re-entering AMO-02-MD-2-004), will not be considered eligible for the study without meeting all of the criteria below:

• Subjects under study must be individuals with a diagnosis of Congenital or Childhood Onset DM1.
• Diagnosis must be genetically confirmed
• Subjects must be male or female aged ≥6 years to ≤45 years at Screening
• Subjects must have a Clinical Global Impression - Severity (CGI-S) score of 3 or greater at Screening (V-1)
• Written, voluntary informed consent must be obtained before any study related procedures are conducted. Where a parent or legally authorized representative (LAR) provides consent, there must also be assent from the subject (as required by local regulations)
• Subject's caregiver must be willing and able to support participation for duration of study
• Subject must be willing and able to comply with the required food intake restrictions as outlined per protocol

Subjects entering directly from completing the antecedent AMO-02-MD-2-003 study will not be considered eligible for the study without meeting all of the criteria below:

• Subjects who have completed the antecedent AMO-02-MD-2-003 study through V11
• Written, voluntary informed consent must be obtained before any study related procedures are conducted. Where a parent or LAR provides consent, there must also be assent from the subject (as required by local regulations)
• Subject's caregiver must be willing and able to support participation for duration of study
• Subject must be willing and able to comply with the required food intake restrictions as outlined per protocol

Критерии исключения

• Body mass index (BMI) less than 13.5 kg/m² or greater than 40 kg/m²
• New or change in medications/therapies within 4 weeks prior to Eligibility/Baseline Visit
• Use within 4 weeks prior to Eligibility/Baseline Visit of strong CYP3A4 inhibitors (eg.clarithromycin, telithromycin, ketoconazole, itraconazole, posaconazole, nefazodone, idinavir and ritonavir)
• Concurrent use of drugs metabolized by CYP3A4 with a narrow therapeutic window (e.g. warfarin and digitoxin)
• Current enrollment in a clinical trial of an investigational drug or enrollment in a clinical trial of an investigational drug in the last 6 months other than the AMO-02- MD-2-003 study
• Existing or historical medical conditions or complications (eg. neurological, cardiovascular, renal, hepatic, gastrointestinal, endocrine or respiratory disease) that may impact the interpretability of the study results
• Hypersensitivity to tideglusib or any components of its formulation including allergy to strawberry

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 10 центров

• Arkansas Children's Hospital — Little Rock
• University of California, Los Angeles (UCLA) — Los Angeles
• Stanford University — Palo Alto
• Lurie's Children's Hospital — Chicago
• University of Iowa Hospitals and Clinics — Iowa City
• University of Rochester - Medical Center — Rochester
• University of Pittsburgh Medical Center — Pittsburgh
• University of Utah Clinical Neurosciences Center — Salt Lake City
• … и ещё 2 центра

Канада · 2 центра

• Children's Hospital London Health Sciences Centre (LHSC) — London
• Children's Hospital of Eastern Ontario — Ottawa

Австралия · 1 центр

• The Bright Alliance — Randwick

Новая Зеландия · 1 центр

• New Zealand Clinical Research (NZCR) — Auckland

Идентификаторы

NCT: NCT05004129 · AMO-02-MD-2-004

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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