Study to Assess the Effects of PTC857 Treatment in Participants With Amyotrophic Lateral Sclerosis ALS

The CAFS is a composite endpoint based on time to earlier occurrence of death and change from baseline in ALSFRS-R score. ALSFRS-R is a rating scale where 12 functions were rated on 5-point scales (from 0 to 4) with a maximum score of 48 (sum of all 12 items), with a higher score indicating better function. Each participant's outcome was compared to every other participant's outcome in a pairwise fashion by time to death and change on ALSFRS-R, assigned a score which was sum of comparisons (+1 [better], 0 [tie], -1 [worse]), and summed scores were ranked, from 1 to 334 (ITT2 Analysis Set) lowest rank corresponds to participant who died first and highest rank to the participant with best ALSFRS-R outcome among those who survived. A higher rank was considered a better outcome. LS mean and SE were calculated using ANCOVA model.

The ALSFRS-R is a quickly administered (5-minute) ordinal rating scale that assesses the participant's capability and independence in 12 functional activities across 4 subdomains of bodily function (bulbar, gross motor, fine motor, and respiratory) relevant in ALS. Each activity was recorded to the closest approximation from a list of 5 choices, scored 0 (total loss of function) to 4 (no loss of function), with the total score ranging from 0 to 48 and higher scores indicating less functional impairment. LS mean and SE were calculated using mixed model repeated measures (MMRM).

The ALSFRS-R is a quickly administered (5-minute) ordinal rating scale that assesses the participant's capability and independence in 12 functional activities across 4 subdomains of bodily function (bulbar, gross motor, fine motor, and respiratory) relevant in ALS. Each activity was recorded to the closest approximation from a list of 5 choices, scored 0 (total loss of function) to 4 (no loss of function), with the total score ranging from 0 to 48 and higher scores indicating less functional impairment. LS mean and SE were calculated using MMRM.

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A TEAE was defined as an AE that began after the first administration of study drug or any existing AEs that worsened after the first dose of study drug. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

The SVC is a measure of breathing function. SVC measures the volume that can be exhaled from a full inhalation after exhaling to a maximum as slowly as possible. The percent of predicted SVC is reported. LS mean and SE were calculated using MMRM.

Modified Norris scale is used to assess the motor/limb and bulbar function. The Modified Norris Scale is a rating scale for ALS that consists of 2 parts: the Limb Norris Scale and the Norris Bulbar Scale. The Limb Norris Scale has 21 items to evaluate extremity function, and the Norris Bulbar Scale has 13 items to evaluate bulbar function. Each item was rated in 4 ordinal categories, corresponding to the following values and ratings or functional scores: normal (3 points), somewhat impaired (2 points), inadequate (1 point), and "cannot do at all" (0 points). The total score was calculated by summing all the scales, ranging from 0 (worst) to 102 (best) where higher scores indicated better functional abilities. LS mean and SE were calculated using MMRM.

Overall survival rate was defined as percentage of participants who were alive at given timepoint. Overall survival was defined as the time in months from the date of first dose to the date of death from any cause or date last known alive for those who did not die.

Overall survival was defined as the time in months from the date of first dose to the date of death from any cause or date last known alive for those who did not die.

The ALSAQ-40 is a disease-specific measure of health-related quality of life (QOL) for ALS. The ALSAQ-40 is comprised of 40 questions measuring 5 discrete dimensions of health status that are affected by the disease: physical mobility (10 items); activities of daily living and independence (10 items); eating and drinking (3 items); communication (7 items); emotional reactions (10 items). Participants were asked to indicate the frequency of each event by selecting one of 5 options (Likert scale: 0-4): never/rarely/sometimes/often/ always or cannot do at all. The total score ranging from 0 (no impairment) to 160 (severe impairment) was calculated by adding the 5 domain scores. A lower score indicates a better health state. LS mean and SE were calculated using MMRM.

The NfL is a marker of axonal degeneration and is robustly elevated in the blood of many neurological and neurodegenerative conditions.