Safety, Immunogenicity and Efficacy Against of a Combined Malaria Vaccine in Healthy Malaria-naïve Adults
2019年6月4日 更新者：GlaxoSmithKline
Safety, Immunogenicity and Efficacy Against Malaria in the Sporozoite Challenge Model of One Dose of Ad35.CS.01 Malaria Vaccine Followed by Two Doses of Malaria 257049 Vaccine in Healthy Malaria-naïve Adults
This study will evaluate whether administration of two investigational malaria vaccines (257049 and Ad35.CS.01 vaccines) combined in one immunization schedule increases protection against malaria infection as compared to protection induced by the 257049 vaccine alone.
The study will also evaluate the safety and the immune response to the new combination of the two experimental malaria vaccines.
調査の概要
状態
完了
条件
詳細な説明
Approximately 168 healthy, malaria-naïve volunteers aged 18 - 50 years, divided into 2 groups (84 in each group), will receive either one dose of Ad35.CS.01 followed by two doses of 257049 at monthly intervals or 3 doses of 257049 vaccine at monthly intervals.
Of these, a maximum of 138 vaccinated volunteers will be challenged with P. falciparum infected mosquitoes.
The challenge will occur 2 weeks following the third immunization.
A group of up to 18 infectivity controls will begin participation in the study at the challenge stage.
These controls receive no vaccine and are enrolled for malaria-challenge only in order to provide comparison group for vaccinated individuals.
研究の種類
介入
入学 (実際)
67
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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Maryland
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Silver Spring、Maryland、アメリカ、20910
- GSK Investigational Site
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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～50年 (大人)
健康ボランティアの受け入れ
はい
受講資格のある性別
全て
説明
Inclusion Criteria:
- Subjects who the investigator believes can and will comply with the requirements of the protocol.
- A male or non-pregnant female 18 to 50 years of age at the time of first vaccination.
- Written informed consent obtained from the subject before screening procedures.
- Free of obvious health problems as established by medical history and clinical examination before entering into the study.
- Available to participate for the duration of the study.
- Female subjects of non-childbearing potential.
Female subjects of childbearing potential may be enrolled in the study, if the subject:
- has practiced adequate Food and Drug Administration (FDA)-approved contraception for 30 days prior to vaccination, and
- has a negative pregnancy test on the day of vaccination, and
- has agreed to continue adequate FDA-approved contraception during the entire treatment period and for 2 months after completion of the vaccination series and/or malaria challenge.
- Pass a comprehension assessment test.
Exclusion Criteria:
- Use of any investigational or non-registered product within 30 days preceding the first dose of study vaccine, or planned use of any investigational or non-registered product other than the study vaccines during the study period.
- Planned administration/ administration of a vaccine not foreseen by the study protocol within 7 days of the first dose of vaccines.
- Prior receipt of an investigational malaria or adenovirus vaccine.
- Chronic use of antibiotics with antimalarial effects.
- History of malaria chemoprophylaxis within 60 days prior to vaccination.
- Any history of malaria.
- Planned travel to malaria endemic areas during the study period.
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s) including latex.
- History of allergic disease or reactions likely to be exacerbated by chloroquine.
- History of psoriasis and porphyria, which may be exacerbated after chloroquine treatment.
- Current use of medications known to cause drug reactions to chloroquine, such as antacids and kaolin.
- Any history of anaphylaxis in reaction to any previous vaccination.
- History of severe reactions to mosquito bites.
- Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
- Chronic administration of immunosuppressants or other immune modifying drugs within six months prior to first vaccine dose.
- Any confirmed or suspected immunosuppressive or immunodeficient condition, including immunodeficiency virus (HIV) infection.
- Family history of congenital or hereditary immunodeficiency.
- History of splenectomy.
- Major congenital defects or serious chronic illness.
- History of any neurological disorders or seizures.
- Acute disease and/or fever at the time of enrollment.
- Acute disease is defined as the presence of a moderate or severe illness with or without fever. Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
- Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
- Any abnormal baseline laboratory screening tests.
- Evidence of increased cardiovascular disease risk, "moderate" or "high", according to the NHANES I criteria.
- An abnormal baseline screening electrocardiogram (EKG).
- Hepatomegaly, right upper quadrant abdominal pain or tenderness.
- Personal history of autoimmune disease.
- Seropositive for hepatitis B surface antigen or Hepatitis C virus (antibodies to HCV).
- Pregnant or lactating female.
- Female who intends to become pregnant during the study or planning to discontinue contraceptive measures.
- Suspected or known current alcohol abuse.
- Chronic or active intravenous drug use.
- History of blood donation within 56 days preceding enrolment.
- Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this 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：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：トリプル
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：Ad35.CS.01 Group
Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm.
The duration of the study was approximately 11 months for vaccinated subjects.
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One dose will be administered intramuscularly at Study Day 0.
Two doses will be administered intramuscularly at monthly intervals
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実験的：GSK257049 Group
Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm.
The duration of the study was approximately 11 months for vaccinated subjects.
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Three doses will be administered intramuscularly at monthly intervals
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実験的：Control Group
Healthy male or non-pregnant female subjects, aged 18 to 50 years, were volunteers who did not receive any immunization but were subjected to the sporozoite challenge.
The duration of the study was approximately 8 months for infectivity control subjects.
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Subjects were challenged with sporozoite-infected mosquitoes to determine whether immune protective response had been induced by vaccination.
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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 |
|---|---|---|
|
Number of Subjects With Plasmodium Falciparum Parasitemia Following Sporozoite Challenge
時間枠：28 days following sporozoite challenge (Day 105)
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P. falciparum parasitemia was defined as a positive blood slide.
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28 days following sporozoite challenge (Day 105)
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Number of Subjects With Any and Grade 3 Solicited Local Symptoms
時間枠：Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination
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Assessed solicited local symptoms were pain, redness and swelling.
Any = occurrence of the symptom regardless of intensity grade.
Grade 3 pain = significant pain at rest, pain that prevented normal every day activities.
Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.
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Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination
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Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
時間枠：Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination
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Assessed solicited general symptoms were chills, fatigue, gastrointestinal symptoms, headache and temperature [defined as axillary temperature equal to or above (≥) 38 degrees Celsius (°C)].
Any = occurrence of the symptom regardless of intensity grade.Grade 3 Chills = rigors [uncontrollable shivering more than (>) 15 seconds].
Grade 3 Fatigue, Gastrointestinal symptoms and Headache = symptoms that prevented normal activity.
Grade 3 fever = fever higher than (>) 39.0 °C.
Related = symptom assessed by the investigator as related to the vaccination.
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Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination
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Number of Subjects With Any Unsolicited Adverse Events (AEs)
時間枠：Within the 30-day (Day 0 - Day 29) follow-up period post-vaccination
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An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
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Within the 30-day (Day 0 - Day 29) follow-up period post-vaccination
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Number of Subjects With Any Unsolicited Adverse Events (AEs)
時間枠：Within the 30-day (Day 0 - Day 29) follow-up period post-challenge
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An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
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Within the 30-day (Day 0 - Day 29) follow-up period post-challenge
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Number of Subjects With Serious Adverse Events (SAEs)
時間枠：Throughout the study period (Day 0 - Day 236)
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Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
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Throughout the study period (Day 0 - Day 236)
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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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Number of Days Until the Onset of P. Falciparum Parasitemia Following Sporozoite Challenge
時間枠：From day of challenge (Day 0) up to 159 days post-challenge
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The onset of P. falciparum parasitemia was defined by a positive blood slide.
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From day of challenge (Day 0) up to 159 days post-challenge
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Anti-circumsporozoite Protein (Anti-CS) Antibody Titers
時間枠：28 days post-dose 1 (Day 28), 28 days post-dose 2 (Day 56), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)
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Titers are presented as geometric mean titers (GMTs) and are measured in titers.
Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore GMTs for this group are presented as from Day 77.
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28 days post-dose 1 (Day 28), 28 days post-dose 2 (Day 56), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)
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Anti-hepatitis B (Anti-HBs) Antibody Titers
時間枠：28 days post-dose 1 (Day 28), 28 days post-dose 2 (Day 56), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)
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Titers are presented as geometric mean titers (GMTs) and are measured in titers.
Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore GMTs for this group are presented as from Day 77.
|
28 days post-dose 1 (Day 28), 28 days post-dose 2 (Day 56), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)
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Anti-Adenovirus Type 35 (Ad35) Neutralizing Antibody Titers at Specified Time Points
時間枠：28 days post-dose 1 (Day 28), 28 days post-dose 2 (Day 56), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)
|
Titers are presented as geometric mean titers (GMTs) and are measured in titers.
Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore GMTs for this group are presented as from Day 77.
|
28 days post-dose 1 (Day 28), 28 days post-dose 2 (Day 56), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)
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Frequency of CS (Total CS or Repeat)-Specific CD4+ T-cells
時間枠：14 days post-dose 1 (Day 14), 14 days post-dose 2 (Day 42), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)
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CS-specific CD4+ T-cells expressing at least 2 cytokines/activation markers between IL-2, IFN-γ, TNF-α and CD40-L are presented here.
Analysis was performed via intra-cellular staining (ICS) assays, data are presented as frequency of T-cells per million peripheral blood mononuclear cells (PBMCs).Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore the frequency for this group is presented as from Day 77.
|
14 days post-dose 1 (Day 14), 14 days post-dose 2 (Day 42), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)
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Frequency of CS (Total CS or Repeat)-Specific CD8+ T Cells
時間枠：14 days post-dose 1 (Day 14), 14 days post-dose 2 (Day 42), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)
|
CS-specific CD8+ T-cells expressing at least 2 cytokines/activation markers between IL-2, IFN-γ, TNF-α and CD40-L are presented here.
Analysis was performed via intra-cellular staining (ICS) assays, data are presented as frequency of T-cells per million peripheral blood mononuclear cells (PBMC).
Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore the frequency for this group is presented as from Day 77.
|
14 days post-dose 1 (Day 14), 14 days post-dose 2 (Day 42), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)
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Frequency of HBs-specific CD4+ T-cells
時間枠：14 days post-dose 1 (Day 14), 14 days post-dose 2 (Day 42), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)
|
HB-specific CD4+ T-cells expressing at least 2 cytokines/activation markers between IL-2, IFN-γ, TNF-α and CD40-L are presented here.
Analysis was performed via intra-cellular staining (ICS) assays, data are presented as frequency of T-cells per million peripheral blood mononuclear cells (PBMCs).
Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore the frequency for this group is presented as from Day 77.
|
14 days post-dose 1 (Day 14), 14 days post-dose 2 (Day 42), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)
|
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Frequency of CS-specific T-cells Producing IFN-γ
時間枠：14 days post-dose 1 (Day 14), 14 days post-dose 2 (Day 42), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)
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The analysis was performed via Enzyme-Linked Immunospot (ELISPOT) full length assay.
Data are presented as the number of spots per million peripheral blood mononuclear cells (PBMCs).
Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore the frequency for this group is presented as from Day 77.
|
14 days post-dose 1 (Day 14), 14 days post-dose 2 (Day 42), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)
|
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Frequency of CS-specific T-cells Producing IFN-γ
時間枠：14 days post-dose 1 (Day 14)
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The analysis was performed via Enzyme-Linked Immunospot (ELISPOT) N-terminal assay.
Data are presented as the number of spots per million peripheral blood mononuclear cells (PBMCs).
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14 days post-dose 1 (Day 14)
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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。
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)
2011年8月10日
一次修了 (実際)
2012年2月27日
研究の完了 (実際)
2012年7月3日
試験登録日
最初に提出
2011年6月2日
QC基準を満たした最初の提出物
2011年6月2日
最初の投稿 (見積もり)
2011年6月6日
学習記録の更新
投稿された最後の更新 (実際)
2019年6月18日
QC基準を満たした最後の更新が送信されました
2019年6月4日
最終確認日
2019年6月1日
詳しくは
本研究に関する用語
その他の研究ID番号
- 114460
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
はい
IPD プランの説明
Patient-level data for this study is available via the Clinical Study Data Request site (click on the link provided below)
IPD 共有時間枠
Patient-level data for this study is available via the Clinical Study Data Request site (click on the link provided below)
IPD 共有アクセス基準
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place.
Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
試験データ・資料
-
臨床研究報告書
情報識別子：114460情報コメント：For additional information about this study please refer to the GSK Clinical Study Register
-
研究プロトコル
情報識別子：114460情報コメント：For additional information about this study please refer to the GSK Clinical Study Register
-
データセット仕様
情報識別子：114460情報コメント：For additional information about this study please refer to the GSK Clinical Study Register
-
個人参加者データセット
情報識別子：114460情報コメント：For additional information about this study please refer to the GSK Clinical Study Register
-
インフォームド コンセント フォーム
情報識別子：114460情報コメント：For additional information about this study please refer to the GSK Clinical Study Register
-
統計分析計画
情報識別子：114460情報コメント：For additional information about this study please refer to the GSK Clinical Study Register
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。