Trial Outcomes & Findings for Study of Tideglusib in Adolescent and Adult Patients With Myotonic Dystrophy (NCT NCT02858908)

Subjects were to be male or female aged 12 to 45 years with a diagnosis of genetically confirmed congenital or juvenile-onset type 1 myotonic dystrophy. Subjects were to have a Clinical Global Impression- Severity (CGI-S) score of 4 or greater at Screening and Run-in (V2) and were to be ambulatory and able to complete the 10-metre walk/run test.

Study of Tideglusib in Adolescent and Adult Patients With Myotonic Dystrophy

Incidence of Adverse events (AEs), including serious adverse events (SAEs), between baseline to end of study.

Pharmacokinetic samples were collected to determine Tideglusib plasma concentration

Pharmacokinetic samples were collected to determine time of the maximum plasma concentration and terminal elimination half-life 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

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.

Handgrip myometry is used as a measure of myotonia and muscle strength for the dominant hand

FVC is a measure of lung function (the total amount of air exhaled during a Forced Expiratory Volume is measured using a spirometer)

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

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.

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.

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.

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.

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.

Measure of fine manual dexterity. Time to taken to complete the NHPT (dominant hand) is recorded.

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.

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).

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.

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.

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.

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.