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 Biosciences
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 Biosciences:

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00647296

  Show 21 Study Locations
Sponsors and Collaborators
Knopp Biosciences
Investigators
Study Director: Evan Ingersoll, Ph.D. Knopp Neurosciences Inc.
  More Information

No publications provided

Responsible Party: Knopp Biosciences
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 Biosciences:
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
Motor Neuron Disease
Sclerosis
Central Nervous System Diseases
Metabolic Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Diseases
Pathologic Processes
Proteostasis Deficiencies
Spinal Cord Diseases
TDP-43 Proteinopathies
Pramipexole
Anti-Dyskinesia Agents
Antioxidants
Antiparkinson Agents
Central Nervous System Agents
Dopamine Agents
Dopamine Agonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014