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

Phase 3RecruitingNCT05004129

AMO Pharma Limited76 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Congenital Myotonic Dystrophy

Interventions

TideglusibDRUG

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.

Eligibility

Sex: ALLMin age: 6 YearsMax age: 45 Years

Medical Language ↔ Plain English

Inclusion Criteria: 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: 1. Subjects under study must be individuals with a diagnosis of Congenital or Childhood Onset DM1. 2. Diagnosis must be genetically confirmed 3. Subjects must be male or female aged ≥6 years to ≤45 years at Screening 4. Subjects must have a Clinical Global Impression - Severity (CGI-S) score of 3 or greater at Screening (V-1) 5. 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) 6. Subject's caregiver must be willing and able to support participation for duration of study 7. 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: 1. Subjects who have completed the antecedent AMO-02-MD-2-003 study through V11 2. 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) 3. Subject's caregiver must be willing and able to support participation for duration of study 4. Subject must be willing and able to comply with the required food intake restrictions as outlined per protocol Key Exclusion Criteria: 1. Body mass index (BMI) less than 13.5 kg/m² or greater than 40 kg/m² 2. New or change in medications/therapies within 4 weeks prior to Eligibility/Baseline Visit 3. Use within 4 weeks prior to Eligibility/Baseline Visit of strong CYP3A4 inhibitors (eg.clarithromycin, telithromycin, ketoconazole, itraconazole, posaconazole, nefazodone, idinavir and ritonavir) 4. Concurrent use of drugs metabolized by CYP3A4 with a narrow therapeutic window (e.g. warfarin and digitoxin) 5. 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 6. 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 7. Hypersensitivity to tideglusib or any components of its formulation including allergy to strawberry

Locations (14)

Arkansas Children's Hospital

Little Rock, Arkansas, United States

RECRUITING

University of California, Los Angeles (UCLA)

Outcomes

Primary Outcomes

Safety (Adverse Events)

The incidence of AEs, including SAEs, and abnormal findings in objective assessments (e.g. laboratory values, ECGs and vital signs) from Screening to Enrolment (where applicable), from Enrolment to End of Treatment (52 Weeks), and End of Treatment to the End of Follow-up period.

Time frame: 52 Weeks

Safety (Adverse Events) - With Optional Expanded Access

The incidence of AEs, including SAEs, and abnormal findings in objective assessments (e.g. laboratory values, ECGs and vital signs) from End of Treatment to End of Optional Extended Access, and End of Optional Extended Access to the End of Follow-up period.

Time frame: 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)

The Clinician-completed Congenital DM1 Rating Scale is an 11-item rating scale completed by the clinician to score the symptom severity of domains that are clinically relevant in Congenital DM1.

Time frame: 52 Weeks

Secondary Outcomes

Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS) - With Optional Expanded Access

The Clinician-completed Congenital DM1 Rating Scale is an 11-item rating scale completed by the clinician to score the symptom severity of domains that are clinically relevant in Congenital DM1.

Time frame: 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)

The CGI-I requires the clinician to rate how much the subject's illness has changed (improved, worsened or stayed the same) relative to a baseline state.

Time frame: 54 Weeks

Data from ClinicalTrials.gov

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Los Angeles, California, United States

ENROLLING_BY_INVITATION

Stanford University

Palo Alto, California, United States

ENROLLING_BY_INVITATION

Lurie's Children's Hospital

Chicago, Illinois, United States

RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

RECRUITING

University of Rochester - Medical Center

Rochester, New York, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

RECRUITING

University of Utah Clinical Neurosciences Center

Salt Lake City, Utah, United States

RECRUITING

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

WITHDRAWN

Virginia Commonwealth University-Department of Neurology - Muscular Dystrophy Translational Research Program

Richmond, Virginia, United States

COMPLETED

...and 4 more locations

Clinical Global Impressions Improvement Scale (CGI-I) - With Optional Expanded Access

The CGI-I requires the clinician to rate how much the subject's illness has changed (improved, worsened or stayed the same) relative to a baseline state.

Time frame: 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

The Top 3 concerns VAS allows caregivers to identify their main three causes of concern, related to the subject's myotonic dystrophy, rather than these being pre-specified within a scale and then rating how these concerns have changed at specific time-points during the study.

Time frame: 54 weeks

Top 3 Caregiver Concerns Visual Analogue Scale (VAS) score - With Optional Expanded Access

Time frame: 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)

CC-CDM1-RS provides a caregiver assessment of the subject on symptoms that may occur in individuals with CDM1. There are a total of 11 symptoms that the caregiver is asked to rate from 0 to 4 based on overall severity.

Time frame: 52 weeks

Caregiver Completed Congenital DM1 Rating Scale (CC-CDM1-RS) - With Optional Expanded Access

Time frame: 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)

The CGI-S is a 7-point Likert type scale that requires the clinician to rate the severity of the subject's illness at the time of assessment, relative to the clinician's past experience with subjects who have the same diagnosis.

Time frame: 54 weeks

Clinical Global Impressions Severity Scale (CGI-S) - With Optional Expanded Access

Time frame: Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132

Autism Behavior Inventory- Clinician (ABI-C)

ABI-C is a 14 item rating scale requires the clinician to assess the core features of Autism Spectrum Disorder as well as common associated behaviors.

Time frame: 52 Weeks

Socialization, Communication, Daily Living, and Adaptive Behavior Composite standard scores of the Vineland Adaptive Behavior Scale - Survey Interview

The Vineland Adaptive Behavior Scales require the clinician to measure personal and social skills needed for everyday living. It provides a targeted assessment of adaptive behavior via a semi-structured parent or caregiver interview.

Time frame: 52 Weeks

10-meter walk-run test

The 10-meter walk/run test is a performance measure used to assess walking speed in meters per second over a short distance. It can be used as an assessment of functional mobility.

Time frame: 52 Weeks

Plasma Troponin T levels

Troponin T can be used as a biomarker for cardiac dysfunction but can also be elevated in DM1 patients without evident cardiac dysfunction.

Time frame: 52 Weeks

Plasma Troponin T levels - With Optional Expanded Access

Troponin T can be used as a biomarker for cardiac dysfunction but can also be elevated in DM1 patients without evident cardiac dysfunction.

Time frame: Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132

Blood Leukocytes CTG Repeats

A genomic blood sample will be taken from all subjects to confirm the average number of repeats at sampling and estimate the number of leukocyte CTG repeats inherited for an individual subject.

Time frame: Baseline and Week 52

Blood Leukocytes CTG Repeats - With Optional Expanded Access

A genomic blood sample will be taken from all subjects to confirm the average number of repeats at sampling and estimate the number of leukocyte CTG repeats inherited for an individual subject. For subjects that have already passed Week 52 at implementation of this endpoint, a single genomic blood sample will taken at the next in-clinic OEA visit.

Time frame: Week 52 or later