Safety and Tolerability Study of KNS-760704 in Amyotrophic Lateral Sclerosis (ALS) (CL201)
2021年6月16日 更新者：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.
調査の概要
状態
完了
条件
詳細な説明
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).
研究の種類
介入
入学 (実際)
194
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Arkansas
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Little Rock、Arkansas、アメリカ、72205
- University of Arkansas for Medical Sciences
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California
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Los Angeles、California、アメリカ、90095
- UCLA, Dept. of Neurology - Neuromuscular/ALS Research Center
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San Francisco、California、アメリカ、94115
- The Forbes Norris MDA/ALS Research Center
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Colorado
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Aurora、Colorado、アメリカ、80045
- University of Colorado Health Sciences Center
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Florida
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Miami、Florida、アメリカ、33136
- University of Miami Miller School of Medicine
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Kansas
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Kansas City、Kansas、アメリカ、66160
- University of Kansas Medical Center
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Maryland
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Baltimore、Maryland、アメリカ、21228
- Johns Hopkins University School Of Medicine
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Massachusetts
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Boston、Massachusetts、アメリカ、02129
- Massachusettes General Hospital
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Missouri
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Saint Louis、Missouri、アメリカ、63110
- Washington University School of Medicine
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Nebraska
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Lincoln、Nebraska、アメリカ、68506
- Bryan LGH Medical Center East
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New York
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New York、New York、アメリカ、10032
- Columbia University, Lou Gehrig MDA/ALS Research Center
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Syracuse、New York、アメリカ、13210
- SUNY Upstate Medical University
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Oregon
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Portland、Oregon、アメリカ、97239
- Oregon Health Sciences University
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Pennsylvania
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Hershey、Pennsylvania、アメリカ、17033
- Penn State Hershey Medical Center
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Philadelphia、Pennsylvania、アメリカ、19102
- Drexel University College of Medicine
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Pittsburgh、Pennsylvania、アメリカ、15213
- University of Pittsburgh School of Medicine
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Tennessee
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Nashville、Tennessee、アメリカ、37232
- Vanderbilt University Medical Center
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Texas
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San Antonio、Texas、アメリカ、78229
- University of Texas Health Sciences Center of San Antonio
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Utah
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Salt Lake City、Utah、アメリカ、84132
- University of Utah
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Virginia
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Charlottesville、Virginia、アメリカ、22908
- University of Virginia Health System
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Washington
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Seattle、Washington、アメリカ、98195
- University of Washington
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
21年～80年 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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プラセボコンパレーター：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
他の名前：
Dexpramipexole: 2 x 37.5 mg tablets taken orally twice daily
他の名前：
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
他の名前：
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実験的：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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実験的：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
他の名前：
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
時間枠：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
時間枠：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
時間枠：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
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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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
時間枠：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
時間枠：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
時間枠：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.
|
4 weeks
|
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Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results
時間枠：4 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 laboratory test.
|
4 weeks
|
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Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings
時間枠：4 weeks
|
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
時間枠：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
時間枠：4 weeks
|
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)
時間枠：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
時間枠：up to 76 weeks
|
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
時間枠：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
|
|
Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group
時間枠：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
|
|
Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group
時間枠：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
|
|
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
時間枠：28 weeks
|
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.
|
28 weeks
|
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Part 2 Double-Blind Treatment: Slope of Percent Predicted Upright Vital Capacity From Baseline by Treatment Group
時間枠：Baseline of randomized phase of Part 2 to week 28 of randomized phase of Part 2
|
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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2008年4月9日
一次修了 (実際)
2009年7月31日
研究の完了 (実際)
2009年9月4日
試験登録日
最初に提出
2008年3月26日
QC基準を満たした最初の提出物
2008年3月28日
最初の投稿 (見積もり)
2008年3月31日
学習記録の更新
投稿された最後の更新 (実際)
2021年7月8日
QC基準を満たした最後の更新が送信されました
2021年6月16日
最終確認日
2021年3月1日
詳しくは
本研究に関する用語
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。