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

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

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.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: KNS-760704

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Los Angeles, California, United States, 90095
      • UCLA, Dept. of Neurology - Neuromuscular/ALS Research Center
    • San Francisco, California, United States, 94115
      • The Forbes Norris MDA/ALS Research Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21228
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02129
      • Massachusettes General Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Bryan LGH Medical Center East
  • New York
    • New York, New York, United States, 10032
      • Columbia University, Lou Gehrig MDA/ALS Research Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19102
      • Drexel University College of Medicine
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh School of Medicine
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Sciences Center of San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient has provided signed informed consent for this trial before the commencement of any study-related procedure
2. 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:

1. Patient did not participate in Knopp Protocol KNS-760704-CL201 or patient did not receive RTPB under Research IND #60,948.
2. Patient discontinued from KNS-760704-CL201 for any reason other than enrollment into this study (applies to patients enrolled in KNS-760704-CL201 only)
3. 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: KNS-760704 300 mg/day; Open-label KNS-760704 (150 mg Q12H)	Drug: KNS-760704; 150 mg Q12H KNS-760704 given orally (300 mg total daily dose); Other Names: dexpramipexole

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Knopp Biosciences
• Investigators: Principal Investigator: Merit Cudkowicz, M.D., MSc, NeuroClinical Trials Unit (Massachusetts General Hospital)

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (ACTUAL): July 1, 2013
• Study Completion (ACTUAL): July 1, 2013

Study Registration Dates

• First Submitted: June 30, 2009
• First Submitted That Met QC Criteria: June 30, 2009
• First Posted (ESTIMATE): July 2, 2009

Study Record Updates

• Last Update Posted (ACTUAL): August 16, 2021
• Last Update Submitted That Met QC Criteria: July 22, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; ALS; Motor Neuron Disease; Nervous System Diseases; Lou Gehrig's disease; Lou Gehrig; Lou Gehrig's; KNS-760704; RTPB
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dopamine Agonists; Dopamine Agents; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Pramipexole
• Other Study ID Numbers: KNS-760704-CL211