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

NCT ID: NCT00647296

Last Updated: 2021-07-08

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

194 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-04-09

Study Completion Date

2009-09-04

Brief Summary

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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.

Detailed Description

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This study was a two-part, multicenter, double-blind study in subjects with ALS to evaluate the safety and tolerability of dexpramipexole treatment, as well as the preliminary effects on measures of clinical function and mortality of dexpramipexole treatment.

In part 1, 102 subjects with ALS were randomized at 20 US sites to receive placebo, dexpramipexole at 50 mg/day; dexpramipexole at 150 mg/day; or dexpramipexole at 300 mg/day for 12 weeks. Participants who completed Part 1 were eligible to enroll into Part 2.

Part 2 was a randomized, double-blind, 2-arm, parallel-group, extension study evaluating the longer-term safety, tolerability, and clinical effects of oral administration of 2 dosage levels of dexpramipexole. In part 2, following a 4-week, placebo washout, continuing subjects received dexpramipexole at 50 mg/day or 300 mg/day as double-blind treatment for up to 72 additional weeks (Part 2 duration was up to a total of 76 weeks, including the 4 week placebo portion).

Conditions

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Amyotrophic Lateral Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Matching placebo during Part 1 and Part 2 placebo washout.

Study Groups

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Part 1: Placebo or Dexpramipexole

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo: 2 tablets taken orally twice daily

Dexpramipexole 50 mg/day

Intervention Type DRUG

Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily

Dexpramipexole 150 mg/day

Intervention Type DRUG

Dexpramipexole: 2 x 37.5 mg tablets taken orally twice daily

Dexpramipexole 300 mg/day

Intervention Type DRUG

Dexpramipexole: 2 x 75 mg tablets taken orally twice daily

Part 2: Placebo washout

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

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Placebo: 2 tablets taken orally twice daily

Part 2: Dexpramipexole

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.

Group Type EXPERIMENTAL

Dexpramipexole 50 mg/day

Intervention Type DRUG

Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily

Dexpramipexole 300 mg/day

Intervention Type DRUG

Dexpramipexole: 2 x 75 mg tablets taken orally twice daily

Interventions

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Placebo

Placebo: 2 tablets taken orally twice daily

Intervention Type DRUG

Dexpramipexole 50 mg/day

Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily

Intervention Type DRUG

Dexpramipexole 150 mg/day

Dexpramipexole: 2 x 37.5 mg tablets taken orally twice daily

Intervention Type DRUG

Dexpramipexole 300 mg/day

Dexpramipexole: 2 x 75 mg tablets taken orally twice daily

Intervention Type DRUG

Other Intervention Names

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KNS-760704 BIIB050 KNS-760704 BIIB050 KNS-760704 BIIB050

Eligibility Criteria

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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 vital capacity (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
Minimum Eligible Age

21 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Knopp Biosciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

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

Los Angeles, California, United States

Site Status

The Forbes Norris MDA/ALS Research Center

San Francisco, California, United States

Site Status

University of Colorado Health Sciences Center

Aurora, Colorado, United States

Site Status

University of Miami Miller School of Medicine

Miami, Florida, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Site Status

Massachusettes General Hospital

Boston, Massachusetts, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Bryan LGH Medical Center East

Lincoln, Nebraska, United States

Site Status

Columbia University, Lou Gehrig MDA/ALS Research Center

New York, New York, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

Oregon Health Sciences University

Portland, Oregon, United States

Site Status

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Drexel University College Of Medicine

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

University of Texas Health Sciences Center of San Antonio

San Antonio, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

University of Virginia Health System

Charlottesville, Virginia, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 22101764 (View on PubMed)

Other Identifiers

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KNS-760704-CL201

Identifier Type: -

Identifier Source: org_study_id

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