Study of Tideglusib in Adolescent and Adult Patients With Myotonic Dystrophy

A Single-Blind, Phase 2 Study To Evaluate The Safety And Efficacy Of Tideglusib 400mg Or 1000mg For The Treatment Of Adolescent And Adult Congenital And Juvenile-Onset Myotonic Dystrophy

The purpose of this study is to determine whether Tideglusib is safe and efficacious in the treatment of adolescents and adults with congenital and juvenile-onset Myotonic Dystrophy. The pharmacokinetics of tideglusib and its primary metabolite will also be investigated.

Study Overview

• Status: Completed
• Conditions: Myotonic Dystrophy 1
• Intervention / Treatment: Drug: Tideglusib

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United Kingdom
  • Tyne and Wear
    • Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE1 4LP
      • Newcastle-upon-Tyne Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adolescents or adults with diagnosis of congenital or juvenile-onset type 1 myotonic dystrophy (DM-1)
• Diagnosis must be genetically confirmed
• Subjects must be male or female aged 12 years to 45 years
• Subjects must have a Clinical Global Impression - Severity (CGI-S) score of 4 or greater at Screening and Run-in (V2)
• Subjects must be ambulatory and able to complete the 10 metre walk/run test (splints allowed)
• Subject's legally authorized representative (LAR) must provide written informed consent and there must be written consent or assent (as age applicable and developmentally appropriate) by the subject before any study-related procedures are conducted

Exclusion Criteria:

• Non-ambulatory (full time) wheel chair user
• Receiving stimulant medication
• Receiving other medications/therapies not stable (changed) within 4 weeks prior to Run-in (V2)
• Medical illness or other concern which would cause investigator to conclude subjects will not be able to perform the study procedures or assessments or would confound interpretation of data obtained during assessment.
• Current enrolment in a clinical trial of an investigational drug or enrolment in a clinical trial of an investigational drug in the last 6 months
• Women of child bearing potential who are pregnant, lactating or not willing to use a protocol defined acceptable contraception method if sexually active and not surgically sterile.
• Gastrointestinal disease which may interfere with the absorption, distribution, metabolism or excretion of the study medication and impact the interpretability of the study results
• Current clinically significant (as determined by the investigator) cardiovascular, renal, hepatic, endocrine or respiratory disease
• Clinically significant heart disease (in the opinion of the investigator) or second or third degree heart block, atrial flutter, atrial fibrillation, ventricular arrhythmias, or is receiving medication for treatment of a cardiac arrhythmia
• A history of chronic liver disease with current out of range values for Alanine transaminase (ALT), clinically relevant hepatic steatosis or other clinical manifestations of ongoing liver disease
• A history of significant drug allergy (such as Steven-Johnson syndrome, anaphylaxis)
• A history of alcohol or substance use disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 - Tideglusib; 1000 mg tideglusib, orally, once daily	Drug: Tideglusib; Tideglusib for oral suspension,
Experimental: Cohort 2 - Tideglusib; 400 mg tideglusib, orally, once daily	Drug: Tideglusib; Tideglusib for oral suspension,

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety (Adverse Events)	Incidence of Adverse events (AEs), including serious adverse events (SAEs), between baseline to end of study.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration of Tideglusib	Pharmacokinetic samples were collected to determine Tideglusib plasma concentration	12 weeks
Blood Pharmacokinetics of Tideglusib	Pharmacokinetic samples were collected to determine time of the maximum plasma concentration and terminal elimination half-life of tideglusib	12 weeks
Area Under the Plasma Concentration vs. Time Curve of Tideglusib	Pharmacokinetic samples were collected to determine area under the plasma concentration vs. time curve from 0 to 12 h and area under the plasma concentration vs. time curve from 0 to 24 h of tideglusib	12 weeks
10 Metre Walk/Run Test	The 10-metre walk/run test is a performance measure used to assess walking speed in metres per second over a short distance and was used as an assessment of functional mobility. Time taken to complete the 10m walk/run test at fastest and preferred speed is measured.	12 weeks
Computerised Handgrip Myometer Measure of Grip Strength and Muscle Relaxation Time	Handgrip myometry is used as a measure of myotonia and muscle strength for the dominant hand	12 weeks
Respiratory Forced Vital Capacity (FVC)	FVC is a measure of lung function (the total amount of air exhaled during a Forced Expiratory Volume is measured using a spirometer)	12 weeks
Dual-energy X-ray Absorptiometry (DXA)	DXA utilises two low energy X-ray beams, with different energy levels, which are aimed at the subject's bones. The DXA scan is more typically used to measure bone mineral density, however it can also be used to measure total lean muscle mass	12 weeks
Clinical Global Impressions- Severity (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. Considering total clinical experience, a subject is assessed on severity of illness at the time of rating 1, normal, not at all ill; 2, borderline ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. Change in CGI-S was observed in only 1 subject. Consequently statistical analysis was not conducted.	12 weeks
Clinical Global Impressions- Improvement (CGI-I)	The CGI-I requires the clinician to rate how much the subject's illness has improved or worsened relative to a baseline state. A seven point Likert type scale is used from 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse.	12 weeks
Actigraphy (3-minute Bouts of Activity)	Actigraphy is a non-invasive method of monitoring physical activity via an actigraph device. The actigraph device was worn on the waist during waking hours, according to the device's instruction manual.	12 weeks
Actigraphy (>10-minute Bouts of Activity)	Actigraphy is a non-invasive method of monitoring physical activity via an actigraph device. The actigraph device was worn on the waist during waking hours, according to the device's instruction manual.	12 weeks
Actigraphy (Steps)	Actigraphy is a non-invasive method of monitoring physical activity via an actigraph device. The actigraph device was worn on the waist during waking hours, according to the device's instruction manual.	12 weeks
Nine Hole Peg Test (NHPT)	Measure of fine manual dexterity. Time to taken to complete the NHPT (dominant hand) is recorded.	12 weeks
Top 3 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. Subjects, where possible, and caregivers were asked to rate three causes for concern by drawing a vertical mark on a 10 cm long visual analogue scale with anchors of "not at all severe" at the left end (0 cm) and "very severe" at the right end (10 cm). A score for each concern was to be determined by measuring the number of centimeters on the 10 cm VAS line from the anchor point on the left side of the line. A total VAS score for each subject was calculated as the sum of the scores for the 3 concerns (minimum = 0 cm, maximum = 30 cm). A higher score represents a worse outcome.	12 weeks
Ohio State University (OSU) Autism Rating Scale (OARS)	The OARS-4 contains the autism signs and symptoms in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. These were to be rated with the degree of impairment the subject experiences for the given symptom. The symptoms were to be elicited in a semi-structured interview with the subject's primary caregiver. The assessor was to take both frequency/duration and degree of impairment into account and how much the item interferes with relationships, learning, and/or activities of daily living. The scores for this assessment were from 0 (Never or Rarely; Not a Problem) to 3 (Very Often; A Severe Problem): a score for each symptom of social impairment, communication impairment and restricted patterns were averaged to provide a total impairment score. A higher score represents a worse outcome (minimum = 0, maximum 3).	12 weeks
Ohio State University (OSU) Autism Clinical Global Impression (CGI)	The OSU Autism CGI scale contains separate subscales for symptom severity and for global improvement. These are rated in a similar way to the National Institute of Mental Health (NIMH) CGI Severity scale, but it is focused on autism spectrum symptoms. OSU Autism CGI-severity and OSU Autism CGI-improvement scores use a seven point Likert rating scale from 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse.	12 weeks
Clinician-completed Domain Specific Cause for Concern Visual Analogue Scale (VAS): Myotonic Dystrophy	The Clinician-completed Domain Specific Causes for Concern is a Visual Analogue Scale completed by the clinician that scores the severity of concerns of domains that are clinically relevant in myotonic dystrophy. The severity of the clinician's concern is scored by using a 10 cm visual analogue scale (VAS), with anchors of "not at all severe" at the left end (0 cm) and "very severe" at the right end (10 cm). The clinician is asked to make a vertical line indicating his/her level of concern in each domain, using a time frame of the past week for reference. A score is to be determined by measuring the number of centimeters on the 10 cm VAS line from the anchor point on the left side of the line. A total VAS score for each subject was calculated as the sum of the scores for the 17 domains (minimum = 0, maximum = 170 cm). A higher score represents a worse outcome.	12 weeks
Peabody Picture Vocabulary Test (PPVT)	The PPVT-4 scale is a norm-referenced instrument for measuring the receptive (hearing) vocabulary of children and adults. It contains training items and 228 test items, each consisting of four full-colour pictures as response options on a page. For each item, the examiner says a word, and the examinee responds by selecting the picture that best illustrates that word's meaning. Each administration of the test produces a raw score (number of test items answered correctly), which can be converted to a standard score (using age-based norms) with a mean of 100 and a standard deviation of 15. Higher scores mean a better performance/receptive vocabulary.	12 weeks
Biomarker - Lymphocyte GSK3β Levels and Activity	Total levels of GSK3β protein was determined via x-MAP technology in a Luminex 200 platform using the AKT Pathway Total Multispecies 7-Plex Panel from ThermoFisher Scientific.	12 weeks

Collaborators and Investigators

• Sponsor: AMO Pharma Limited
• Investigators: Principal Investigator: Grainne Gorman, MB BCh BAO LRCP&SI MRCP FRCP, Institute of Neuroscience, Newcastle University.

Publications and helpful links

General Publications

• Horrigan J, Gomes TB, Snape M, Nikolenko N, McMorn A, Evans S, Yaroshinsky A, Della Pasqua O, Oosterholt S, Lochmuller H. A Phase 2 Study of AMO-02 (Tideglusib) in Congenital and Childhood-Onset Myotonic Dystrophy Type 1 (DM1). Pediatr Neurol. 2020 Nov;112:84-93. doi: 10.1016/j.pediatrneurol.2020.08.001. Epub 2020 Aug 5.

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2016
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: August 4, 2016
• First Submitted That Met QC Criteria: August 4, 2016
• First Posted (Estimated): August 8, 2016

Study Record Updates

• Last Update Posted (Estimated): September 11, 2025
• Last Update Submitted That Met QC Criteria: August 22, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Muscular Disorders, Atrophic; Muscular Dystrophies; Myotonic Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myotonic Dystrophy; tideglusib
• Other Study ID Numbers: AMO-02-MD-2-001; 2016-000067-16 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No