Anti-TF Antibody (ALT-836) to Treat Septic Patients With Acute Lung Injury or Acute Respiratory Distress Syndrome
2015年3月20日 更新者：Altor BioScience
Efficacy and Safety Evaluation of ALT-836 in Patients With Sepsis and Acute Lung Injury/Acute Respiratory Distress Syndrome
This is a prospective, randomized (1:1), double-blind, multi-center, Phase II clinical study to test the safety and efficacy of a recombinant chimeric anti-tissue factor antibody (ALT-836) versus placebo in patients with sepsis and acute lung injury/acute respiratory distress syndrome (ALI/ARDS).
This study was divided into two parts and the first part of the study has been completed.
In the first part of the study, sixty patients were randomized at a 1:1 ratio to receive one dose of the study drug or placebo.
In the second part of the study, ninety patients will be randomized at a 1:1 ratio to receive a multi-dose treatment regimen of single doses every 72 hours up to a maximum of 4 doses of the study drug or placebo, provided there are no safety concerns.
調査の概要
詳細な説明
Tissue factor (TF)-dependent procoagulant activity and associated inflammatory processes may play a role in the severity and progression of ALI/ARDS.
Recent studies demonstrated that TF levels were elevated in plasma and pulmonary edema fluid of ARDS/ALI patients compared to control patients with hydrostatic pulmonary edema.
These higher plasma TF levels were correlated with increased mortality, fewer ventilation-free days, the presence of disseminated intravascular coagulation and the presence of sepsis in patients with ALI/ARDS, suggesting that systemic activation of coagulation may be clinically important in ALI/ARDS.
Moreover, the pulmonary TF levels in patients with ALI/ARDS were found to range between 0.5 and 2 nM, approximately 100-fold higher than simultaneous plasma levels, suggesting an intra-alveolar source of TF.
Thus, anti-TF antibody blockage of TF activity may therefore provide an effective therapeutic mechanism for the treatment of inflammatory disorders such as ALI and ARDS.
This study will test the hypothesis that administration of anti-TF antibody (ALT-836) to septic patients with ALI/ARDS will improve the clinical outcome by shortening the duration of mechanical ventilation for these patients.
研究の種類
介入
入学 (実際)
150
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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California
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Los Angeles、California、アメリカ、90033
- Los Angeles County and USC Medical Center
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Sacramento、California、アメリカ、95817
- UC Davis Medical Center
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Stanford、California、アメリカ、94305
- Stanford University
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Connecticut
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New Haven、Connecticut、アメリカ、06520
- Yale University
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Illinois
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Chicago、Illinois、アメリカ、60611
- Northwestern University
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Oak Park、Illinois、アメリカ、60302
- West Suburban Hospital Medical Center
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Peoria、Illinois、アメリカ、61606
- Illinois Lung and Critical Care Institute
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Iowa
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Iowa City、Iowa、アメリカ、52246
- University of Iowa
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Kentucky
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Hazard、Kentucky、アメリカ、41701
- Kentucky Lung Clinic
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Louisville、Kentucky、アメリカ、40202
- University of Louisville-Division of Pulmonary and Critical Care
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Massachusetts
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Springfield、Massachusetts、アメリカ、01199
- Baystate Medical Center
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Missouri
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Kansas City、Missouri、アメリカ、64111
- Saint Luke's Hospital
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St. Louis、Missouri、アメリカ、63110
- Saint Louis University
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St. Louis、Missouri、アメリカ、63141
- Mercy Hospital St. Louis
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New York
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New York、New York、アメリカ、10065
- Memorial Sloan-Kettering Cancer Center
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New York City、New York、アメリカ、10029
- Mount Sinai Medical Center
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North Carolina
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Charlotte、North Carolina、アメリカ、28203
- Carolinas Medical Center
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Greensboro、North Carolina、アメリカ、27310
- Piedmont Respiratory Research Foundation
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Winston-Salem、North Carolina、アメリカ、27157
- Wake Forest University
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Oklahoma
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Oklahoma City、Oklahoma、アメリカ、73104
- University of Oklahoma
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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
18年歳以上 (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:
- Suspected or proven infection
- Hypoxemia: PaO2/FiO2is ≤300 mm Hg
- Bilateral infiltrates consistent with pulmonary edema
- Positive-pressure mechanical ventilation through an endotracheal tube
- No clinical evidence of left atrial hypertension to explain bilateral infiltrates
- Presence of at least three of the four SIRS criteria. If only two criteria are evidenced, one must be temperature or WBC
Criteria 2 and 3 must occur within a 24-hour interval. The 48-hour enrollment time window begins when criteria 2, 3, and 4 are met.
EXCLUSION CRITERIA:
- <18 years
- Inability to obtain consent
- Patient, surrogate, or physician not committed to full support
- Moribund state in which death was perceived to be imminent
- Morbid obesity
- Malignancy or other irreversible disease or condition for which 6-month mortality is estimated to be >50%
- Known HIV positive with known end stage processes
- Prior cardiac arrest requiring CPR without fully demonstrated neurological recovery; or New York Heart Association Class IV
- Pregnant or nursing
- ALI/ARDS induced by mechanical or chemical injury directly to the lung (including burns, trauma, and near drowning)
- >48 hours since all inclusion criteria are met
- Neuromuscular disease that impairs ability to ventilate without assistance
- Severe chronic respiratory disease, severe pulmonary hypertension, or ventilator dependency
- Chest wall deformity resulting in severe exercise restriction, secondary polycythemia, or respirator dependent
- History of organ transplant (including bone marrow)
- Severe chronic liver disease, as determined by a Child-Pugh Score >10
- Hemoglobin persistently < 7.0 g/dL
- Platelet count <50,000/mm3
- Prolonged INR >3
- Bleeding disorders unless corrective surgery has been performed
- Active internal bleeding
- Major surgery within 24 hours before study drug infusion, or evidence of active bleeding postoperatively, or plan for any major surgery within 3 days after study drug infusion.
- Diffuse alveolar hemorrhage from vasculitis
- Known bleeding diathesis
- Presence of an epidural catheter or lumbar puncture within 48 hours before study drug infusion or anticipation of receiving an epidural catheter or a lumbar puncture within 48 hours after study drug infusion
- Stroke within 3 months of study entry
- Trauma with an increased risk of life-threatening bleeding
- A history of severe head trauma that required hospitalization, or intracranial surgery within two months of study entry
- Any history of intracerebral arteriovenous malformation, cerebral aneurysm, or central nervous system mass lesion
- Uses of certain medications or treatment regimens such as chemotherapy, unfractionated heparin, low-molecular-weight heparin, Warfarin, antithrombin III, acetylsalicylic acid, glycoprotein IIb/IIIa antagonists, thrombolytic therapy, and activated Protein C are restricted.
- Participation in another experimental medication study within 30 days of study entry.
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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実験的：1
Participants will be randomized to receive ALT-836.
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In the first part of this study, recombinant chimeric anti-tissue factor antibody ALT-836 was administered as a single dose (0.06 mg/Kg) via intravenous infusion over 15 minutes.
In the second part of this study, up to four doses (0.06 mg/Kg) of ALT-836 will be administered via intravenous infusion over 15 minutes.
他の名前：
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プラセボコンパレーター：2
Patients will be randomized to receive placebo.
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In the first part of this study, a single dose of Placebo was administered via intravenous infusion over 15 minutes.
In the second part of this study, up to four doses of Placebo will be administered via intravenous infusion over 15 minutes.
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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 |
時間枠 |
|---|---|
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Safety profile of the study drug
時間枠：Throughout the 28 days following treatment
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Throughout the 28 days following treatment
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Number of ventilator-free days at Day 28
時間枠：Determined at Day 28
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Determined at Day 28
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
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Mortality at Day 7, 14, 21, 28 and 60
時間枠：Determined at Day 7, 14, 21, 28 and 60
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Determined at Day 7, 14, 21, 28 and 60
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Length of hospitalization at Day 28
時間枠：Determined at Day 28
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Determined at Day 28
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Length of ICU stay at Day 28
時間枠：Determined at Day 28
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Determined at Day 28
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Number of Non-pulmonary organ failure free days at Day 28
時間枠：Determined at Day 28
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Determined at Day 28
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Changes in physiological variables of lung injury
時間枠：Throughout the 28 days following treatment
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Throughout the 28 days following treatment
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Changes in disease severity and lung injury scores
時間枠：Throughout the 28 days following treatment
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Throughout the 28 days following treatment
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Effects of the study drug and the etiology of the disease (i.e. pulmonary or extra-pulmonary origin)
時間枠：Determined at Day 28
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Determined at Day 28
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Pharmacokinetics & Pharmacodynamics
時間枠：Throughout the 28 days following treatment
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Throughout the 28 days following treatment
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Immunogenicity
時間枠：Throughout the 28 days following treatment
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Throughout the 28 days following treatment
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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
捜査官
- スタディチェア：Hing C Wong, PhD、Altor BioScience
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
2009年4月1日
一次修了 (実際)
2012年10月1日
研究の完了 (実際)
2013年1月1日
試験登録日
最初に提出
2009年4月8日
QC基準を満たした最初の提出物
2009年4月8日
最初の投稿 (見積もり)
2009年4月10日
学習記録の更新
投稿された最後の更新 (見積もり)
2015年4月10日
QC基準を満たした最後の更新が送信されました
2015年3月20日
最終確認日
2015年3月1日
詳しくは
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。