Safety and Tolerability Study of KNS-760704 in Amyotrophic Lateral Sclerosis (ALS) (CL201)
keskiviikko 16. kesäkuuta 2021 päivittänyt: Knopp Biosciences
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.
Tutkimuksen yleiskatsaus
Tila
Valmis
Yksityiskohtainen kuvaus
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).
Opintotyyppi
Interventio
Ilmoittautuminen (Todellinen)
194
Vaihe
- Vaihe 2
Yhteystiedot ja paikat
Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.
Opiskelupaikat
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Arkansas
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Little Rock, Arkansas, Yhdysvallat, 72205
- University of Arkansas for Medical Sciences
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California
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Los Angeles, California, Yhdysvallat, 90095
- UCLA, Dept. of Neurology - Neuromuscular/ALS Research Center
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San Francisco, California, Yhdysvallat, 94115
- The Forbes Norris MDA/ALS Research Center
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Colorado
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Aurora, Colorado, Yhdysvallat, 80045
- University of Colorado Health Sciences Center
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Florida
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Miami, Florida, Yhdysvallat, 33136
- University of Miami Miller School of Medicine
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Kansas
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Kansas City, Kansas, Yhdysvallat, 66160
- University of Kansas Medical Center
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Maryland
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Baltimore, Maryland, Yhdysvallat, 21228
- Johns Hopkins University School Of Medicine
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Massachusetts
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Boston, Massachusetts, Yhdysvallat, 02129
- Massachusettes General Hospital
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Missouri
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Saint Louis, Missouri, Yhdysvallat, 63110
- Washington University School of Medicine
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Nebraska
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Lincoln, Nebraska, Yhdysvallat, 68506
- Bryan LGH Medical Center East
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New York
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New York, New York, Yhdysvallat, 10032
- Columbia University, Lou Gehrig MDA/ALS Research Center
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Syracuse, New York, Yhdysvallat, 13210
- SUNY Upstate Medical University
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Oregon
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Portland, Oregon, Yhdysvallat, 97239
- Oregon Health Sciences University
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Pennsylvania
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Hershey, Pennsylvania, Yhdysvallat, 17033
- Penn State Hershey Medical Center
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Philadelphia, Pennsylvania, Yhdysvallat, 19102
- Drexel University College of Medicine
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Pittsburgh, Pennsylvania, Yhdysvallat, 15213
- University of Pittsburgh School of Medicine
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Tennessee
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Nashville, Tennessee, Yhdysvallat, 37232
- Vanderbilt University Medical Center
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Texas
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San Antonio, Texas, Yhdysvallat, 78229
- University of Texas Health Sciences Center of San Antonio
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Utah
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Salt Lake City, Utah, Yhdysvallat, 84132
- University of Utah
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Virginia
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Charlottesville, Virginia, Yhdysvallat, 22908
- University of Virginia Health System
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Washington
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Seattle, Washington, Yhdysvallat, 98195
- University of Washington
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Osallistumiskriteerit
Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.
Kelpoisuusvaatimukset
Opintokelpoiset iät
21 vuotta - 80 vuotta (Aikuinen, Vanhempi Aikuinen)
Hyväksyy terveitä vapaaehtoisia
Ei
Sukupuolet, jotka voivat opiskella
Kaikki
Kuvaus
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
Opintosuunnitelma
Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Nelinkertaistaa
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
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Placebo Comparator: 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.
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Placebo: 2 tablets taken orally twice daily
Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily
Muut nimet:
Dexpramipexole: 2 x 37.5 mg tablets taken orally twice daily
Muut nimet:
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Muut nimet:
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Kokeellinen: Part 2: Placebo washout
At the beginning of Part 2, subjects received twice daily doses of placebo for approximately 4 weeks.
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Placebo: 2 tablets taken orally twice daily
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Kokeellinen: 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.
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Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily
Muut nimet:
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Muut nimet:
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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
Aikaikkuna: 12 weeks
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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.
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12 weeks
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Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group
Aikaikkuna: 12 weeks
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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.
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12 weeks
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Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group
Aikaikkuna: 12 weeks
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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.
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12 weeks
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Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group
Aikaikkuna: 12 weeks
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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.
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12 weeks
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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group
Aikaikkuna: 12 weeks
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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.
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12 weeks
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Part 1: Slope of Upright Vital Capacity From Baseline to Week 12 by Treatment Group
Aikaikkuna: 12 weeks
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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.
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12 weeks
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Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Hematology
Aikaikkuna: 4 weeks
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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.
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4 weeks
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Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results
Aikaikkuna: 4 weeks
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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.
|
4 weeks
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Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings
Aikaikkuna: 4 weeks
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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.
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4 weeks
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Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements
Aikaikkuna: 4 weeks
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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.
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4 weeks
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Part 2 Placebo Washout: Absolute Change in ALSFRS-R Total Score
Aikaikkuna: 4 weeks
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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. |
4 weeks
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Part 2 Placebo Washout: Absolute Change in Upright Vital Capacity (Percent Predicted) From Baseline to End of Placebo Washout (Week 4)
Aikaikkuna: 4 weeks
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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.
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4 weeks
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Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
Aikaikkuna: up to 76 weeks
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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.
|
up to 76 weeks
|
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Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group
Aikaikkuna: up to 76 weeks
|
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.
|
up to 76 weeks
|
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Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group
Aikaikkuna: up to 76 weeks
|
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.
|
up to 76 weeks
|
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Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group
Aikaikkuna: up to 76 weeks
|
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.
|
up to 76 weeks
|
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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
Aikaikkuna: 28 weeks
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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.
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28 weeks
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Part 2 Double-Blind Treatment: Slope of Percent Predicted Upright Vital Capacity From Baseline by Treatment Group
Aikaikkuna: Baseline of randomized phase of Part 2 to week 28 of randomized phase of Part 2
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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.
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Baseline of randomized phase of Part 2 to week 28 of randomized phase of Part 2
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Opintojen ennätyspäivät
Nämä päivämäärät seuraavat ClinicalTrials.gov-sivustolle lähetettyjen tutkimustietueiden ja yhteenvetojen edistymistä. National Library of Medicine (NLM) tarkistaa tutkimustiedot ja raportoidut tulokset varmistaakseen, että ne täyttävät tietyt laadunvalvontastandardit, ennen kuin ne julkaistaan julkisella verkkosivustolla.
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Keskiviikko 9. huhtikuuta 2008
Ensisijainen valmistuminen (Todellinen)
Perjantai 31. heinäkuuta 2009
Opintojen valmistuminen (Todellinen)
Perjantai 4. syyskuuta 2009
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Keskiviikko 26. maaliskuuta 2008
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Perjantai 28. maaliskuuta 2008
Ensimmäinen Lähetetty (Arvio)
Maanantai 31. maaliskuuta 2008
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Torstai 8. heinäkuuta 2021
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Keskiviikko 16. kesäkuuta 2021
Viimeksi vahvistettu
Maanantai 1. maaliskuuta 2021
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
- Patologiset prosessit
- Metaboliset sairaudet
- Keskushermoston sairaudet
- Hermoston sairaudet
- Neuromuskulaariset sairaudet
- Neurodegeneratiiviset sairaudet
- Selkäydinsairaudet
- TDP-43 Proteinopatiat
- Proteostaasin puutteet
- Skleroosi
- Motorinen neuronitauti
- Amyotrofinen lateraaliskleroosi
- Huumeiden fysiologiset vaikutukset
- Neurotransmitterit
- Farmakologisen vaikutuksen molekyylimekanismit
- Suojaavat aineet
- Dopamiiniagonistit
- Dopamiini-aineet
- Antioksidantit
- Parkinsonin vastaiset aineet
- Dyskinesian vastaiset aineet
- Pramipeksoli
Muut tutkimustunnusnumerot
- KNS-760704-CL201
Nämä tiedot haettiin suoraan verkkosivustolta clinicaltrials.gov ilman muutoksia. Jos sinulla on pyyntöjä muuttaa, poistaa tai päivittää tutkimustietojasi, ota yhteyttä register@clinicaltrials.gov. Heti kun muutos on otettu käyttöön osoitteessa clinicaltrials.gov, se päivitetään automaattisesti myös verkkosivustollemme .