Background: This is a phase 2, randomized, double-blind, placebo-controlled, parallel study to assess the effects of PTC857 treatment in adult male and female subjects diagnosed with ALS. The objectives of the study are to evaluate the efficacy, safety, tolerability, PK, and effects on biomarkers of PTC857 therapy in subjects with ALS. The study consists of 5 periods: Screening, Treatment, LTE, Continued LTE, and Follow-Up
Placebo-Controlled, Parallel Study to Assess the Efficacy, Safety, Tolerability, PK, and Biomarker Effects of PTC857 in Adult Subjects With Amyotrophic Lateral Sclerosis (CARDINALS)
The entire study duration is approximately 172 weeks:
- Screening Period: Approximately 8 weeks
- Treatment Period (Part A): Approximately 24 weeks
- Long-Term Extension (LTE) Period (Part B): Approximately 28 weeks
- Continued LTE Period (Part C): Approximately 108 weeks
- Post-Treatment Follow-Up Period: Approximately 4 weeks
Primary Objective: To evaluate the efficacy of PTC857 in reducing disease progression in subjects with amyotrophic lateral sclerosis (ALS).
Secondary Objectives: The secondary objectives of the study are to assess the following in subjects with ALS: 1. Safety and tolerability of PTC857 2. Respiratory function in subjects randomized to PTC857 versus placebo 3. Motor/limb and bulbar function in subjects randomized to PTC857 versus placebo 4. Neuropsychological function in subjects randomized to PTC857 versus placebo 5. Survival in subjects randomized to PTC857 versus placebo 6. Quality of life via 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) in subjects randomized to PTC857 versus placebo 7. Pharmacokinetics (PK) of PTC857.
Endpoints: Disease progression as assessed by the ALSFRS-R score: The ALSFRS-R is a quickly administered (5-minute) ordinal rating scale that assesses the subjects’ capability and independence in 12 functional activities across 4 subdomains of bodily function (bulbar, gross motor, fine motor, and breathing) relevant in ALS. Each activity is 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 better function.
Respiratory function as assessed by PFTs: Pulmonary function tests will assess slow vital capacity and Sniff Nasal Inspiratory Pressure (SNIP). Forced vital capacity, vital capacity, forced expiratory volume, and maximum inspiratory pressure will not be measured. Oxygen saturation (SpO2), respiratory rate, and heart rate will be assessed in both upright and supine positions. The SNIP test will assess nasal pressure in each unilaterally occluded nostril during a maximal sniff to assess inspiratory muscle strength.
Motor/limb and bulbar function as assessed by the Modified Norris Scale: 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 is rated in 4 ordinal categories. PTC857-CNS-001-ALS Clinical Protocol V5.0 PTC Therapeutics - Confidential Page 12 of 93
Neuropsychological function as assessed by the ALS CBS: The ALS CBS is a measure of cognition and behavior in patients with ALS. The cognitive section assesses attention, concentration, tracking/monitoring, and initiation and retrieval. The behavioral section compares changes in personality and behavior since the onset of ALS, as well as mood, pseudobulbar affect, and fatigue.
Disease-specific measure of health-related quality of life as assessed by ALSAQ-40: The ALSAQ-40 is a disease-specific measure of health-related quality of life for ALS. It is specifically used to measure the subjective well-being of patients with ALS and provides scores for 5 scales: physical mobility, activities of daily living and independence, eating and drinking, communication, and emotional reactions.
Health-related quality of life as assessed by EQ-5D-5L: The EQ-5D-5L is used for respondents to rate their own health in 5 different dimensions, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Status: The study is fully completed and will finish in 2025.