Safety and Tolerability Study of KNS-760704 in Amyotrophic Lateral Sclerosis (ALS) (CL201)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Knopp Neurosciences
ClinicalTrials.gov Identifier:
NCT00647296
First received: March 26, 2008
Last updated: August 8, 2013
Last verified: August 2013
  Purpose

This is a 2-part study of KNS-760704 in patients with ALS.

  • Part 1 is a randomized, placebo-controlled, multi-center study to evaluate the safety, tolerability, and clinical effects of oral administration of 3 dosage levels of KNS 760704 vs. placebo for 12 weeks.
  • Part 2 is a randomized, double-blind, 2-arm, parallel group, extension study evaluating the safety, tolerability, and clinical effects of oral administration of 2 dosage levels of KNS-760704 for up to 76 weeks.

Condition Intervention Phase
Amyotrophic Lateral Sclerosis
Drug: KNS-760704
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 2-Part, Randomized, Double-Blind, Safety and Tolerability Study Evaluating KNS-760704 in Patients With Amyotrophic Lateral Sclerosis (ALS)

Resource links provided by NLM:


Further study details as provided by Knopp Neurosciences:

Primary Outcome Measures:
  • Number of subjects experiencing unacceptable safety or tolerability events after oral administration of KNS-760704 compared to placebo for 12 weeks in subjects with ALS (Part 1) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of subjects experiencing unacceptable safety or tolerability events after oral administration of KNS-760704 compared to placebo for up to 76 weeks in subjects with ALS (Part 2) [ Time Frame: 76 weeks ] [ Designated as safety issue: Yes ]
  • Change from Baseline in ALSFRS-R [ Time Frame: 12 weeks (part 1) and 28 weeks (part 2) ] [ Designated as safety issue: Yes ]
  • Change from baseline to Week 12 in upright and supine vital capacity [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Changes in cystatin C and neurofilament H [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 102
Study Start Date: March 2008
Study Completion Date: October 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: matched placebo Drug: Placebo
Placebo oral tablet (2 tabs twice daily) for 12 weeks
Experimental: low-dose KNS-760704 Drug: KNS-760704
Oral tablet 2 x 12.5 mg twice daily for 12 weeks
Experimental: mid-dose KNS-760704 Drug: KNS-760704
Oral tablet 2 x 37.5 mg twice daily for 12 weeks
Experimental: high-dose KNS-760704 Drug: KNS-760704
Oral tablet 2 x 75 mg twice daily for 12 weeks

Detailed Description:

This is a double-blind, randomized, placebo-controlled study evaluating the safety and efficacy of KNS-760704 compared to placebo. The study will be conducted in 2 parts.

In Part 1, approximately 80 eligible patients will be randomized to 1 of 4 treatment groups for 12 weeks of treatment: placebo; low-dose; mid-dose; or high-dose KNS-760704. Participants meeting eligibility requirements will be enrolled at approximately 20 centers in the U.S. In addition to the visit to determine eligibility and the first visit to take study drug, participants will be required to make 5 additional research clinic visits in Part 1.

Participants who complete all 12 weeks of Part 1 will be eligible for randomization to Part 2. The duration of Part 2 of the study is 76 weeks. Subjects will receive 1 of 2 active treatment groups for 72 weeks (low-dose or high-dose KNS-760704) and placebo for the remaining 4-week period in Part 2. Participants will not be told when the 4 weeks of placebo treatment will be given. During Part 2, participants will be required to make 12 research clinic visits, including the baseline visit.

  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with diagnosis of familial or sporadic ALS, defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the World Federation of Neurology El Escorial criteria
  • Patients with ALS symptom onset < 24 months from randomization
  • Patients with upright VC > 65% of predicted for age, height, and gender

Exclusion Criteria:

  • Patients in whom causes of neuromuscular weakness other than ALS have not been excluded
  • Patients without clinical evidence of upper motor neuron dysfunction
  • Patients with clinically suspected ALS according to the World Federation of Neurology El Escorial criteria
  • Patients with prior exposure to KNS-760704 or the R(+) enantiomer of pramipexole (i.e., R(+)-pramipexole)
  • Patients taking other investigational agents (including lithium) within 30 days of randomization or during the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00647296

  Hide Study Locations
Locations
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
UCLA, Dept. of Neurology - Neuromuscular/ALS Research Center
Los Angeles, California, United States, 90095
The Forbes Norris MDA/ALS Research Center
San Francisco, California, United States, 94115
United States, Colorado
University of Colorado Health Sciences Center
Aurora, Colorado, United States, 80045
United States, Florida
University of Miami Miller School of Medicine
Miami, Florida, United States, 33136
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Maryland
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States, 21228
United States, Massachusetts
Massachusettes General Hospital
Boston, Massachusetts, United States, 02129
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Nebraska
Bryan LGH Medical Center East
Lincoln, Nebraska, United States, 68506
United States, New York
Columbia University, Lou Gehrig MDA/ALS Research Center
New York, New York, United States, 10032
SUNY Upstate Medical University
Syracuse, New York, United States, 13210
United States, Oregon
Oregon Health Sciences University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Penn State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Drexel University College Of Medicine
Philadelphia, Pennsylvania, United States, 19102
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
University of Texas Health Sciences Center of San Antonio
San Antonio, Texas, United States, 78229
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22908
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Knopp Neurosciences
Investigators
Study Director: Evan Ingersoll, Ph.D. Knopp Neurosciences Inc.
  More Information

No publications provided

Responsible Party: Knopp Neurosciences
ClinicalTrials.gov Identifier: NCT00647296     History of Changes
Other Study ID Numbers: KNS-760704-CL201
Study First Received: March 26, 2008
Last Updated: August 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Knopp Neurosciences:
ALS
Amyotrophic Lateral Sclerosis
Lou Gehrig
Lou Gehrig's
Lou Gehrig's disease
Motor Neuron Disease
Nervous System Diseases
KNS-760704

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
TDP-43 Proteinopathies
Neuromuscular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Pathologic Processes
Pramipexol
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on April 17, 2014