Safety, Immunogenicity and Efficacy Against of a Combined Malaria Vaccine in Healthy Malaria-naïve Adults
2019년 6월 4일 업데이트: 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.
연구 개요
상태
완전한
정황
상세 설명
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.
연구 유형
중재적
등록 (실제)
67
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Maryland
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Silver Spring, Maryland, 미국, 20910
- GSK Investigational Site
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 (성인)
건강한 자원 봉사자를 받아들입니다
예
연구 대상 성별
모두
설명
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.
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 방지
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 삼루타
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: 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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실험적: 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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실험적: 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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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Number of Subjects With Plasmodium Falciparum Parasitemia Following Sporozoite Challenge
기간: 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
기간: 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
기간: 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)
기간: 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)
기간: 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)
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Number of Days Until the Onset of P. Falciparum Parasitemia Following Sporozoite Challenge
기간: 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
기간: 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
기간: 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-Adenovirus Type 35 (Ad35) Neutralizing Antibody Titers at Specified Time Points
기간: 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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Frequency of CS (Total CS or Repeat)-Specific CD4+ T-cells
기간: 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.
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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
기간: 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 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.
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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
기간: 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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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.
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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
기간: 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.
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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
기간: 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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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2011년 8월 10일
기본 완료 (실제)
2012년 2월 27일
연구 완료 (실제)
2012년 7월 3일
연구 등록 날짜
최초 제출
2011년 6월 2일
QC 기준을 충족하는 최초 제출
2011년 6월 2일
처음 게시됨 (추정)
2011년 6월 6일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2019년 6월 18일
QC 기준을 충족하는 마지막 업데이트 제출
2019년 6월 4일
마지막으로 확인됨
2019년 6월 1일
추가 정보
이 연구와 관련된 용어
기타 연구 ID 번호
- 114460
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
예
IPD 계획 설명
Patient-level data for this study is available via the Clinical Study Data Request site (click on the link provided below)
IPD 공유 기간
Patient-level data for this study is available via the Clinical Study Data Request site (click on the link provided below)
IPD 공유 액세스 기준
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 공유 지원 정보 유형
- 연구_프로토콜
- 수액
- ICF
- CSR
연구 데이터/문서
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임상 연구 보고서
정보 식별자: 114460정보 댓글: For additional information about this study please refer to the GSK Clinical Study Register
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연구 프로토콜
정보 식별자: 114460정보 댓글: For additional information about this study please refer to the GSK Clinical Study Register
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데이터 세트 사양
정보 식별자: 114460정보 댓글: For additional information about this study please refer to the GSK Clinical Study Register
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개별 참가자 데이터 세트
정보 식별자: 114460정보 댓글: For additional information about this study please refer to the GSK Clinical Study Register
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정보에 입각한 동의서
정보 식별자: 114460정보 댓글: For additional information about this study please refer to the GSK Clinical Study Register
-
통계 분석 계획
정보 식별자: 114460정보 댓글: For additional information about this study please refer to the GSK Clinical Study Register
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .