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

NCT00647296 | Completed Phase 2 Results

• 1 other identifier: KNS-760704-CL201
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 21

Brief Summary

This was a 2-part study of dexpramipexole in patients with ALS. Part 1 was a randomized, placebo-controlled, multi-center study to evaluate the safety, tolerability, and clinical effects of oral administration of 3 dosage levels of dexpramipexole vs. placebo for 12 weeks. Part 2 was 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 dexpramipexole for up to 72 weeks.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS; Amyotrophic Lateral Sclerosis; Lou Gehrig; Lou Gehrig's; Lou Gehrig's disease; Motor Neuron Disease; Nervous System Diseases; KNS-760704; BIIB050

Outcome Measures

Primary Outcomes (4)

• Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group

  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.

  12 weeks

• Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group

  Number of Participants with Potentially Clinically Significant Blood Chemistry 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.

  12 weeks

• Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group

  Number of Participants with Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.

  12 weeks

• Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group

  Number of Participants with Potentially Clinically Significant Vital Sign Measurements by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.

  12 weeks

Secondary Outcomes (14)

• Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group

  12 weeks

• Part 1: Slope of Upright Vital Capacity From Baseline to Week 12 by Treatment Group

  12 weeks

• Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Hematology

  4 weeks

• Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results

  4 weeks

• Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings

  4 weeks

Study Arms (3)

Part 1: Placebo or Dexpramipexole

PLACEBO COMPARATOR

During Part 1, subjects received twice daily doses of dexpramipexole (50 mg/day, 150 mg/day, or 300 mg/day) or matching placebo for approximately 12 weeks.

Drug: Placebo; Drug: Dexpramipexole 50 mg/day; Drug: Dexpramipexole 150 mg/day; Drug: Dexpramipexole 300 mg/day

Part 2: Placebo washout

EXPERIMENTAL

At the beginning of Part 2, subjects received twice daily doses of placebo for approximately 4 weeks.

Drug: Placebo

Part 2: Dexpramipexole

EXPERIMENTAL

Following the Part 2 placebo washout, subjects received dexpramipexole (50 mg/day or 300 mg/day), subjects received twice daily doses of placebo for up to 18 months.

Drug: Dexpramipexole 50 mg/day; Drug: Dexpramipexole 300 mg/day

Interventions

Placebo DRUG

Placebo: 2 tablets taken orally twice daily

Part 1: Placebo or Dexpramipexole; Part 2: Placebo washout

Dexpramipexole 50 mg/day DRUG

Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily

Also known as: KNS-760704, BIIB050

Part 1: Placebo or Dexpramipexole; Part 2: Dexpramipexole

Dexpramipexole 150 mg/day DRUG

Dexpramipexole: 2 x 37.5 mg tablets taken orally twice daily

Also known as: KNS-760704, BIIB050

Part 1: Placebo or Dexpramipexole

Dexpramipexole 300 mg/day DRUG

Dexpramipexole: 2 x 75 mg tablets taken orally twice daily

Also known as: KNS-760704, BIIB050

Part 1: Placebo or Dexpramipexole; Part 2: Dexpramipexole

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 vital capacity (VC) \> 65% of predicted for age, height, and gender

You may not qualify if:

• 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

Sponsors & Collaborators

• Knopp Biosciences: lead

Study Sites (21)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

UCLA, Dept. of Neurology - Neuromuscular/ALS Research Center

Los Angeles, California, 90095, United States

Location

The Forbes Norris MDA/ALS Research Center

San Francisco, California, 94115, United States

Location

University of Colorado Health Sciences Center

Aurora, Colorado, 80045, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21228, United States

Location

Massachusettes General Hospital

Boston, Massachusetts, 02129, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Bryan LGH Medical Center East

Lincoln, Nebraska, 68506, United States

Location

Columbia University, Lou Gehrig MDA/ALS Research Center

New York, New York, 10032, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Drexel University College Of Medicine

Philadelphia, Pennsylvania, 19102, United States

Location

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Health Sciences Center of San Antonio

San Antonio, Texas, 78229, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (1)

• Cudkowicz M, Bozik ME, Ingersoll EW, Miller R, Mitsumoto H, Shefner J, Moore DH, Schoenfeld D, Mather JL, Archibald D, Sullivan M, Amburgey C, Moritz J, Gribkoff VK. The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis. Nat Med. 2011 Nov 20;17(12):1652-6. doi: 10.1038/nm.2579.

  PMID: 22101764 RESULT

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Nervous System Diseases

Interventions

Dexpramipexole

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzothiazoles; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Head of Regulatory
• Organization: Knopp Biosciences

greg@knoppbio.com

4124881776

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Matching placebo during Part 1 and Part 2 placebo washout.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2008
• First Posted: March 31, 2008
• Study Start: April 9, 2008
• Primary Completion: July 31, 2009
• Study Completion: September 4, 2009
• Last Updated: July 8, 2021
• Results First Posted: July 8, 2021

Record last verified: 2021-03

Locations

US (21)