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A Study to Evaluate Safety and Immunogenicity of AERAS-402 Administered in HIV-negative, BCG-vaccinated, QFT (+) and (-) Adults Without Evidence of TB (C-012-402)

2016年4月25日 更新者:Aeras

A Phase I Randomized Placebo-controlled Double-blind Study to Evaluate Safety and Immunogenicity of AERAS-402 Administered in HIV-negative, BCG-vaccinated, QuantiFERON®-TB Gold (+) and QuantiFERON®-TB Gold (-) Adults Without Evidence of Tuberculosis.

The available live tuberculosis vaccine Bacillus Calmette-Guérin (BCG) provides incomplete protection against pulmonary tuberculosis. For unknown reasons, a BCG revaccination or "booster", while not toxic, does not provide much additional protection. AERAS-402 presents tuberculosis antigens in the setting of a new, live, replication deficient adenovirus vaccine that may increase T cell immunity and thus protection from tuberculosis. Since BCG-vaccinated individuals are the population for which AERAS-402 might be indicated, AERAS-402 will be administered to individuals in Kenya who have already been vaccinated with BCG.

調査の概要

詳細な説明

This Phase I study will be conducted as a double-blind, randomized, placebo-controlled study in 20 healthy adult subjects. The study will enroll 10 subjects who are QFT-G positive at screening and 10 subjects who are QFT-G negative at screening. Within QFT-G group, subjects will be randomized to receive AERAS-402 or placebo in a ratio of 4:1. One dose level of AERAS-402 (3 x 10^10 vp) will be investigated in this study. All subjects will receive a single dose of study vaccine (AERAS-402 or placebo) on Study Day 0 and a second dose of study vaccine (AERAS-402 or placebo) on Study Day 56. All vaccinations will be administered by IM injection into the deltoid muscle.

The sample size was selected as adequate for preliminary safety evaluations and initial immunogenicity reviews for this phase study, rather than for statistical reasons. If no serious adverse events are observed in 16 subjects who receive AERAS-402, the upper bound of the 95% confidence interval on the rate of serious adverse event occurrence is 17.1 percent.

The selection of AERAS-402 dose level for evaluation in this study was derived from animal studies and based on the safety profile for the completed and ongoing clinical studies in the U.S. and South Africa.The total duration of follow-up is 182 days for each subject with a total of eleven follow-up clinic visits. The study is planned at a single site in Kisumu, Kenya.

研究の種類

介入

入学 (実際)

20

段階

  • フェーズ 1

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

      • Kisumu、ケニア
        • Kenya Medical Research Institute

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~45年 (大人)

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:

  1. Is male or female
  2. Is age 18 through 45 years on Study Day 0
  3. Has completed the written informed consent process
  4. Had BCG vaccination at least 5 years ago, documented through medical history or presence of scar
  5. Females: Ability to avoid pregnancy from 28 days prior to administration of the study vaccine through the end of the study.
  6. Has general good health, confirmed by medical history and physical examination.
  7. Has Body Mass Index (BMI) between 18 and 30 (wt./ht.2) by nomogram
  8. Has ability to complete follow-up period of 182 days as required by the protocol
  9. Is able and willing to commit to avoiding elective surgery for the duration of the study.
  10. Is able and willing to stay in contact with the study site for the duration of the study.
  11. Has completed simultaneous enrollment in Aeras Vaccine Development Registry Protocol.

Exclusion Criteria:

  1. Acute illness on the day of randomization.
  2. Fever ≥37.5°C on the day of randomization.
  3. Evidence of any significant active infection on the day of randomization.
  4. Used immunosuppressive medication within 45 days before entry into the study (inhaled and topical corticosteroids are permitted).
  5. Received immunoglobulin or blood products within 45 days before entry into the study.
  6. Received any investigational drug therapy or vaccine within 182 days before the first dose of study vaccine in this protocol.
  7. Received any standard vaccine within 45 days before the first dose of study vaccine in this protocol, through the last study visit (the use of licensed drugs or vaccines medically indicated during the study is permitted).
  8. Received any adenovector based vaccine previously.
  9. Current chronic drug therapy including hormones such as thyroxin, insulin, etc. (Estrogen and progesterone replacement and contraceptives are permitted)
  10. History or laboratory evidence of any past, present or future possible immunodeficiency state which will include, but is not limited to, any laboratory indication of HIV-1 infection.
  11. History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine.
  12. Previous medical history that may compromise the safety of the subject in the study.
  13. Evidence of a new acute illness that may compromise the safety of the subject in the study.
  14. Pregnant or lactating/nursing females.
  15. Evidence of chronic hepatitis including a positive test for hepatitis B core antibody, or hepatitis C antibody.
  16. Inability to discontinue daily medications except contraceptives during the study.
  17. History of alcohol or drug abuse within the past 2 years.
  18. Tobacco or cannabis smoking three or more days per week
  19. Positive urine test for illicit drugs (opiates, cocaine, amphetamines).
  20. History or evidence of any systemic disease on physical examination or any acute or chronic illness that may interfere with the evaluation of the safety or immunogenicity of the vaccine, including axillary lymphadenopathy
  21. History or evidence (including chest X-ray) of active or past tuberculosis
  22. Abnormal hemoglobin, hematocrit, white blood cell count, absolute neutrophil count, absolute lymphocyte count, PT, PTT, GGT, ALT, AST, total bilirubin, ALP, and creatinine drawn within 36 hours of randomization. CPK must be drawn but the CPK value is not an exclusion criteria.
  23. History of high risk sexual behaviors.

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:防止
  • 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
プラセボコンパレーター:Placebo
1.0 mL sterile buffer administered by intramuscular (IM) injection to deltoid area on days 0 and 56.
This is the identical buffer solution in which AERAS-402 is formulated.
実験的:AERAS-402
1.0 mL containing 3 x 10^10 vp/mL suspended in 20 mM Tris buffer, 2 mM MgCl2, 25 mM NaCl, 10% w/v sucrose, 0.02% w/v PS-80 (polysorbate-80, non-animal source) and water. Administered intramuscular (IM) injection to deltoid area on days 0 and 56.
Given to 8 participants that were QFT-G(-) at screening and 8 participants that were GFT-G(+) at screening.

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
Safety of AERAS-402 in healthy, HIV-negative, BCG-vaccinated, QuantiFERON®-TB Gold In-Tube test (QFT-G)(+) and QFT-G(-) adults without evidence of tuberculosis disease in Kenya.
時間枠:Day 0 thru Day 182
Collection of solicited and unsolicited adverse events.
Day 0 thru Day 182

二次結果の測定

結果測定
メジャーの説明
時間枠
Immunogenicity profile of AERAS-402 in healthy, HIV-negative, BCG-vaccinated, QFT-G(+) and QFT-G(-) adults without evidence of tuberculosis disease in Kenya.
時間枠:Day 0 thru day 182
Percentage of CD4 and CD8 T cells that produce any of three cytokines (IFN-γ, TNF-α, and/or IL-2) or a combination of the three cytokines simultaneously.
Day 0 thru day 182

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

  • 主任研究者:Doug Walsh, MD、U. S. Army Medical Research Unit- Kenya

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

2008年9月1日

一次修了 (実際)

2009年6月1日

研究の完了 (実際)

2010年7月1日

試験登録日

最初に提出

2015年4月27日

QC基準を満たした最初の提出物

2015年4月29日

最初の投稿 (見積もり)

2015年4月30日

学習記録の更新

投稿された最後の更新 (見積もり)

2016年4月27日

QC基準を満たした最後の更新が送信されました

2016年4月25日

最終確認日

2016年4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。

Placeboの臨床試験

3
購読する