Crucell's replication deficient adenovirus type 35 circumsporozoite malaria vaccine (Ad35.CS.01) a GSK Biologicals' malaria vaccine 257049 (2 doses) a GSK Biologicals' malaria vaccine 257049 (3 doses) v roce Malárie - Registr klinických hodnocení

Přehled studie

Postavení

Dokončeno

Podmínky

Malárie

Intervence / Léčba

Detailní popis

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.

Typ studie

Intervenční

Zápis (Aktuální)

67

Fáze

Fáze 2

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

Spojené státy
- Maryland
  - Silver Spring, Maryland, Spojené státy, 20910
    - GSK Investigational Site

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let až 50 let (Dospělý)

Přijímá zdravé dobrovolníky

Ano

Pohlaví způsobilá ke studiu

Všechno

Popis

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.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

Primární účel: Prevence
Přidělení: Randomizované
Intervenční model: Paralelní přiřazení
Maskování: Trojnásobný

Zbraně a zásahy

Skupina účastníků / Arm Skupina účastníků / Arm Skupina nebo podskupina účastníků klinické studie, která podle protokolu studie dostává konkrétní intervenci/léčbu nebo žádnou intervenci.	Intervence / Léčba Intervence / Léčba Proces nebo akce, na které se klinická studie zaměřuje. Intervence zahrnují léky, zdravotnická zařízení, postupy, vakcíny a další produkty, které jsou buď zkoušené nebo již dostupné. Intervence mohou také zahrnovat neinvazivní přístupy, jako je edukace nebo úprava stravy a cvičení.
Experimentální: 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.	Biologický: Crucell's replication deficient adenovirus type 35 circumsporozoite malaria vaccine (Ad35.CS.01) One dose will be administered intramuscularly at Study Day 0. Biologický: GSK Biologicals' malaria vaccine 257049 (2 doses) Two doses will be administered intramuscularly at monthly intervals
Experimentální: 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.	Biologický: GSK Biologicals' malaria vaccine 257049 (3 doses) Three doses will be administered intramuscularly at monthly intervals
Experimentální: 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.	Jiný: Sporozoite challenge Subjects were challenged with sporozoite-infected mosquitoes to determine whether immune protective response had been induced by vaccination.

Co je měření studie?

Primární výstupní opatření

Měření výsledku	Popis opatření	Časové okno
Number of Subjects With Plasmodium Falciparum Parasitemia Following Sporozoite Challenge Časové okno: 28 days following sporozoite challenge (Day 105)	P. falciparum parasitemia was defined as a positive blood slide.	28 days following sporozoite challenge (Day 105)
Number of Subjects With Any and Grade 3 Solicited Local Symptoms Časové okno: Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination	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.	Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Časové okno: Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination	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.	Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination
Number of Subjects With Any Unsolicited Adverse Events (AEs) Časové okno: Within the 30-day (Day 0 - Day 29) follow-up period post-vaccination	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.	Within the 30-day (Day 0 - Day 29) follow-up period post-vaccination
Number of Subjects With Any Unsolicited Adverse Events (AEs) Časové okno: Within the 30-day (Day 0 - Day 29) follow-up period post-challenge	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.	Within the 30-day (Day 0 - Day 29) follow-up period post-challenge
Number of Subjects With Serious Adverse Events (SAEs) Časové okno: Throughout the study period (Day 0 - Day 236)	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.	Throughout the study period (Day 0 - Day 236)

Sekundární výstupní opatření

Měření výsledku	Popis opatření	Časové okno
Number of Days Until the Onset of P. Falciparum Parasitemia Following Sporozoite Challenge Časové okno: From day of challenge (Day 0) up to 159 days post-challenge	The onset of P. falciparum parasitemia was defined by a positive blood slide.	From day of challenge (Day 0) up to 159 days post-challenge
Anti-circumsporozoite Protein (Anti-CS) Antibody Titers Časové okno: 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)
Anti-hepatitis B (Anti-HBs) Antibody Titers Časové okno: 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)
Anti-Adenovirus Type 35 (Ad35) Neutralizing Antibody Titers at Specified Time Points Časové okno: 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)
Frequency of CS (Total CS or Repeat)-Specific CD4+ T-cells Časové okno: 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 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)
Frequency of CS (Total CS or Repeat)-Specific CD8+ T Cells Časové okno: 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)
Frequency of HBs-specific CD4+ T-cells Časové okno: 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)
Frequency of CS-specific T-cells Producing IFN-γ Časové okno: 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)	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)
Frequency of CS-specific T-cells Producing IFN-γ Časové okno: 14 days post-dose 1 (Day 14)	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).	14 days post-dose 1 (Day 14)

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

GlaxoSmithKline

Spolupracovníci

Crucell Holland BV

The PATH Malaria Vaccine Initiative (MVI)

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Ockenhouse CF, Regules J, Tosh D, Cowden J, Kathcart A, Cummings J, Paolino K, Moon J, Komisar J, Kamau E, Oliver T, Chhoeu A, Murphy J, Lyke K, Laurens M, Birkett A, Lee C, Weltzin R, Wille-Reece U, Sedegah M, Hendriks J, Versteege I, Pau MG, Sadoff J, Vanloubbeeck Y, Lievens M, Heerwegh D, Moris P, Guerra Mendoza Y, Jongert E, Cohen J, Voss G, Ballou WR, Vekemans J. Ad35.CS.01-RTS,S/AS01 Heterologous Prime Boost Vaccine Efficacy against Sporozoite Challenge in Healthy Malaria-Naive Adults. PLoS One. 2015 Jul 6;10(7):e0131571. doi: 10.1371/journal.pone.0131571. eCollection 2015.

Užitečné odkazy

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Aktuální)

10. srpna 2011

Primární dokončení (Aktuální)

27. února 2012

Dokončení studie (Aktuální)

3. července 2012

Termíny zápisu do studia

První předloženo

2. června 2011

První předloženo, které splnilo kritéria kontroly kvality

2. června 2011

První zveřejněno (Odhad)

6. června 2011

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

18. června 2019

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

4. června 2019

Naposledy ověřeno

1. června 2019

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

114460

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

ANO

Popis plánu IPD

Patient-level data for this study is available via the Clinical Study Data Request site (click on the link provided below)

Časový rámec sdílení IPD

Patient-level data for this study is available via the Clinical Study Data Request site (click on the link provided below)

Kritéria přístupu pro sdílení IPD

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.

Typ podpůrných informací pro sdílení IPD

PROTOKOL STUDY
MÍZA
ICF
CSR

Studijní data/dokumenty

Zpráva o klinické studii
Identifikátor informace: 114460

Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
Protokol studie
Identifikátor informace: 114460

Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
Specifikace datové sady
Identifikátor informace: 114460

Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
Soubor dat jednotlivých účastníků
Identifikátor informace: 114460

Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
Formulář informovaného souhlasu
Identifikátor informace: 114460

Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
Plán statistické analýzy
Identifikátor informace: 114460

Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

Safety, Immunogenicity and Efficacy Against of a Combined Malaria Vaccine in Healthy Malaria-naïve Adults

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

Přehled studie

Postavení

Podmínky

Intervence / Léčba

Detailní popis

Typ studie

Zápis (Aktuální)

Fáze

Kontakty a umístění

Studijní místa

Kritéria účasti

Kritéria způsobilosti

Věk způsobilý ke studiu

Přijímá zdravé dobrovolníky

Pohlaví způsobilá ke studiu

Popis

Studijní plán

Jak je studie koncipována?

Detaily designu

Počet zbraní

Zbraně a zásahy

Skupina účastníků / Arm

Intervence / Léčba

Co je měření studie?

Primární výstupní opatření

Měření výsledku

Popis opatření

Časové okno

Sekundární výstupní opatření

Měření výsledku

Popis opatření

Časové okno

Spolupracovníci a vyšetřovatelé

Sponzor

Spolupracovníci

Publikace a užitečné odkazy

Obecné publikace

Užitečné odkazy

Termíny studijních záznamů

Hlavní termíny studia

Začátek studia (Aktuální)

Primární dokončení (Aktuální)

Dokončení studie (Aktuální)

Termíny zápisu do studia

První předloženo

První předloženo, které splnilo kritéria kontroly kvality

První zveřejněno (Odhad)

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

Naposledy ověřeno

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

Popis plánu IPD

Časový rámec sdílení IPD

Kritéria přístupu pro sdílení IPD

Typ podpůrných informací pro sdílení IPD

Studijní data/dokumenty