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Amyotrophic Lateral SclerosisPhase 2CL201NCT00647296

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

A Phase 2 study testing Dexpramipexole 50 mg/day, Dexpramipexole 150 mg/day and Dexpramipexole 300 mg/day in people with Amyotrophic Lateral Sclerosis, run by Knopp Biosciences at 21 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 21 to 80 years
Conditions the study is for
Amyotrophic Lateral Sclerosis
What is being tested?
Dexpramipexole 50 mg/day, Dexpramipexole 150 mg/day and Dexpramipexole 300 mg/day
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
194 participants
Where
21 sitesUnited States
Study dates
9 Apr 2008to 4 Sep 2009
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

United States21 sites
  • University of Colorado Health Sciences Center

    Aurora, Colorado, 80045

  • Johns Hopkins University School of Medicine

    Baltimore, Maryland, 21228

  • Massachusettes General Hospital

    Boston, Massachusetts, 02129

  • University of Virginia Health System

    Charlottesville, Virginia, 22908

  • Penn State Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Bryan LGH Medical Center East

    Lincoln, Nebraska, 68506

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

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

    Los Angeles, California, 90095

  • University of Miami Miller School of Medicine

    Miami, Florida, 33136

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Columbia University, Lou Gehrig MDA/ALS Research Center

    New York, New York, 10032

  • Drexel University College Of Medicine

    Philadelphia, Pennsylvania, 19102

  • University of Pittsburgh School of Medicine

    Pittsburgh, Pennsylvania, 15213

  • Oregon Health Sciences University

    Portland, Oregon, 97239

  • University of Utah

    Salt Lake City, Utah, 84132

  • University of Texas Health Sciences Center of San Antonio

    San Antonio, Texas, 78229

  • The Forbes Norris MDA/ALS Research Center

    San Francisco, California, 94115

  • University of Washington

    Seattle, Washington, 98195

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • SUNY Upstate Medical University

    Syracuse, New York, 13210

Other trials in United States

About this study

Official title: A 2-Part, Randomized, Double-Blind, Safety and Tolerability Study Evaluating KNS-760704 in Patients With Amyotrophic Lateral Sclerosis (ALS)

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.

Read the detailed description

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).

Being tested
Placebo, Dexpramipexole 50 mg/day, Dexpramipexole 150 mg/day, Dexpramipexole 300 mg/day
Keywords
ALS, Amyotrophic Lateral Sclerosis, Lou Gehrig, Lou Gehrig's, Lou Gehrig's disease, Motor Neuron Disease, Nervous System Diseases, KNS-760704, BIIB050
Medical subject headings
Amyotrophic Lateral Sclerosis, Motor Neuron Disease, Nervous System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    Placebo: 2 tablets taken orally twice daily

  • Dexpramipexole 50 mg/dayDrug

    Also called KNS-760704, BIIB050

    Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily

  • Dexpramipexole 150 mg/dayDrug

    Also called KNS-760704, BIIB050

    Dexpramipexole: 2 x 37.5 mg tablets taken orally twice daily

  • Dexpramipexole 300 mg/dayDrug

    Also called KNS-760704, BIIB050

    Dexpramipexole: 2 x 75 mg tablets taken orally twice daily

Study groups in NCT00647296
Study groupRoleWhat they receive
Part 1: Placebo or DexpramipexolePlacebo comparatorDuring 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.
Receives: Drug: Placebo; Drug: Dexpramipexole 50 mg/day; Drug: Dexpramipexole 150 mg/day; Drug: Dexpramipexole 300 mg/day
Part 2: Placebo washoutExperimentalAt the beginning of Part 2, subjects received twice daily doses of placebo for approximately 4 weeks.
Receives: Drug: Placebo
Part 2: DexpramipexoleExperimentalFollowing 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.
Receives: Drug: Dexpramipexole 50 mg/day; Drug: Dexpramipexole 300 mg/day

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 12 weeks

  2. 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.

    Measured: 12 weeks

  3. 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.

    Measured: 12 weeks

  4. 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.

    Measured: 12 weeks

Secondary outcomes (14)
  1. Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group

    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, with higher scores representing better function. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis ALSFRS-R score. Units for slope are change per month in units on the ALSFRS-R scale.

    Measured: 12 weeks

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

    Slope of change in Upright Vital Capacity (percent predicted upright vital capacity) from Baseline to Week 12. A negative change/slope indicates clinical worsening. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis as percent predicted upright vital capacity. Units for slope are change per month in percent predicted upright vital capacity.

    Measured: 12 weeks

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

    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.

    Measured: 4 weeks

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

    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.

    Measured: 4 weeks

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

    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.

    Measured: 4 weeks

  6. Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements

    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.

    Measured: 4 weeks

  7. Part 2 Placebo Washout: Absolute Change in ALSFRS-R Total Score

    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, with higher scores representing better function.

    Units are points on the ALSFRS-R score as an absolute change from the baseline of the placebo washout to week 4 of the placebo washout.

    Measured: 4 weeks

  8. Part 2 Placebo Washout: Absolute Change in Upright Vital Capacity (Percent Predicted) From Baseline to End of Placebo Washout (Week 4)

    Absolute change in Upright Vital Capacity From Baseline to Week 4. Units are percent of predicted Upright Vital Capacity. A negative change indicates clinical worsening.

    Measured: 4 weeks

  9. Part 2 Double-Blind Treatment: 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 parameter.

    Measured: up to 76 weeks

  10. Part 2 Double-Blind Treatment: 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 parameter.

    Measured: up to 76 weeks

  11. Part 2 Double-Blind Treatment: 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 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 parameter.

    Measured: up to 76 weeks

  12. Part 2 Double-Blind Treatment: 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 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 parameter.

    Measured: up to 76 weeks

  13. Part 2 Double-Blind Treatment: Slope of the ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 28 by Treatment Group

    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, with higher scores representing better function. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis ALSFRS-R score. Units for slope are change per month n units on the ALSFRS-R scale.

    Measured: 28 weeks

  14. Part 2 Double-Blind Treatment: Slope of Percent Predicted Upright Vital Capacity From Baseline by Treatment Group

    Slope of Upright Vital Capacity (percent predicted) through Week 28. A negative change indicates clinical worsening. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis percent predicted upright vital capacity. Units for slope are change per month in percent predicted upright vital capacity.

    Measured: Baseline of randomized phase of Part 2 to week 28 of randomized phase of Part 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Mar 2008 (estimated)
  2. Study start9 Apr 2008
  3. Primary completion31 Jul 2009
  4. Study completion4 Sep 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
194 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00647296
Sponsor's protocol ID
KNS-760704-CL201
Acronym
CL201
Status last verified
Mar 2021
First submitted
26 Mar 2008
Last updated
8 Jul 2021
Data monitoring committee
No

Publications

  • 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.

    PubMed 22101764

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dexpramipexole 50 mg/day, Dexpramipexole 150 mg/day and Dexpramipexole 300 mg/day in people with Amyotrophic Lateral Sclerosis, run by Knopp Biosciences at 21 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group (time frame: 12 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00647296, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2021.

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