Open-Label, Safety and Tolerability Extension Study of KNS-760704 in Amyotrophic Lateral Sclerosis (ALS) (CL211)

Study Overview
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Brief Summary
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This is an open-label, multi-center study designed to extend the evaluation of the safety, tolerability, and clinical effects of oral administration of KNS-760704 in patients with ALS.

Detailed Description
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Patients who complete the Part 2 Week 28 visit in study KNS-760704-CL201 and patients with ALS who were actively receiving RTPB [(6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazolediamine dihydro-chloride monohydrate] under Research IND #60,948 were eligible to participate in this study. Eligible patients received 1 tablet of KNS-760704 (150 mg) every 12 hours (Q12H) (300 mg total daily dose) for up to 180 weeks.

Official Title
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An Open-Label, Safety and Tolerability, Study Evaluating KNS-760704 in Patients With Amyotrophic Lateral Sclerosis (ALS)

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: KNS-760704


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has provided signed informed consent for this trial before the commencement of any study-related procedure Patient is actively participating in Knopp Protocol KNS-760704-CL201 and has completed the Part 2 Week 28 visit in that study or patient is actively receiving RTPB under Research IND #60,948 Exclusion Criteria: Patient did not participate in Knopp Protocol KNS-760704-CL201 or patient did not receive RTPB under Research IND #60,948. Patient discontinued from KNS-760704-CL201 for any reason other than enrollment into this study (applies to patients enrolled in KNS-760704-CL201 only) Patient was not taking RTPB under Research IND #60,948 prior to April 30, 2009 (applies to patients enrolled under Research IND #60,948 only)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KNS-760704 300 mg/day<br>Open-label KNS-760704 (150 mg Q12H) | Drug: KNS-760704<br>* 150 mg Q12H KNS-760704 given orally (300 mg total daily dose)<br>* Other names: dexpramipexole;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Potentially Clinically Significant Hematology Results | Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test. | 180 weeks | 
| Number of Participants With Potentially Clinically Significant Liver Enzyme Abnormalities | Number of participants with potentially clinically significant liver enzyme abnormalities for the safety population are presented. Percentages are based on the number of patients with at least one non-missing, post-baseline value for each parameter. | 180 weeks | 
| Number of Participants With Potentially Clinically ECG Abnormalities | Number of participants with potentially clinically significant ECG abnormalities for the safety population are presented. Percentages are based on the number of patients in the safety population who had at least one non-missing, post-baseline value. | 180 weeks | 
| Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities | Number of participants with potentially clinically significant vital sign abnormalities for the safety population are presented. Percentages are based on the number of patients with at least one non-missing, post-baseline value for each parameter. | 180 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) Total Score From Baseline to Week 12 | The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48. Therefore, the score ranges from 0 to 48 with higher scores representing better function. | 12 weeks | 
| Change in ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) Total Score From Baseline to Week 24 | The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48. Therefore, the score ranges from 0 to 48 with higher scores representing better function. | 24 weeks | 
| Change in ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) Total Score From Baseline to Week 48 | The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48. Therefore, the score ranges from 0 to 48 with higher scores representing better function. | 48 weeks | 
| Change in Upright Vital Capacity From Baseline to Week 12 | Change in Percent Predicted Upright Vital Capacity from Baseline to Week 12. A negative change indicates clinical worsening. | 12 weeks | 
| Change in Upright Vital Capacity From Baseline to Week 24 | Change in Percent Predicted Upright Vital Capacity from Baseline to Week 24. A negative change indicates clinical worsening. | 24 weeks | 
| Change in Upright Vital Capacity From Baseline to Week 48 | Change in Percent Predicted Upright Vital Capacity from Baseline to Week 48. A negative change indicates clinical worsening. | 48 weeks | 
| Change in McGill Single-Item Scale (SIS) From Baseline to Week 12 | The McGill SIS consists of a single question designed to assess the improvement of or the rate of deterioration of the subject's quality-of-life. Subjects rated their quality of life over the prior 2 days on a scale of 0 (very bad) to 10 (excellent). Decreases from Baseline indicate deterioration of a subject's quality of life. | 12 weeks | 
| Change in McGill Single-Item Scale (SIS) From Baseline to Week 24 | The McGill SIS consists of a single question designed to assess the improvement of or the rate of deterioration of the subject's quality-of-life. Subjects rated their quality of life over the prior 2 days on a scale of 0 (very bad) to 10 (excellent). Decreases from Baseline indicate deterioration of a subject's quality of life. | 24 weeks | 
| Change in McGill Single-Item Scale (SIS) From Baseline to Week 48 | The McGill SIS consists of a single question designed to assess the improvement of or the rate of deterioration of the subject's quality-of-life. Subjects rated their quality of life over the prior 2 days on a scale of 0 (very bad) to 10 (excellent). Decreases from Baseline indicate deterioration of a subject's quality of life. | 48 weeks | 
| Number of Subjects With Feeding Tube Placed During the Study. | Number of participants who had a feeding tube placed during the study. | 144 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KNS-760704, Lou Gehrig, ALS, Amyotrophic Lateral Sclerosis, Lou Gehrig's, Lou Gehrig's disease, Motor Neuron Disease, Nervous System Diseases, RTPB