Clinical trial NCT01366534: Safety, Immunogenicity and Efficacy Against of a Combined Malaria Vaccine in Healthy Malaria-naïve Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria
Keywords: safety
Vaccine
Phase 1/2
immunogenicity
Malaria
efficacy
sporozoite challenge
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: The PATH Malaria Vaccine Initiative (MVI)
name: Crucell Holland BV
First posted: 2011-06-06
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Subjects With Plasmodium Falciparum Parasitemia Following Sporozoite Challenge
timeFrame: 28 days following sporozoite challenge (Day 105)
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: Within the 30-day (Day 0 - Day 29) follow-up period post-vaccination
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: Within the 30-day (Day 0 - Day 29) follow-up period post-challenge
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: Throughout the study period (Day 0 - Day 236)
Secondary outcomes:
measure: Number of Days Until the Onset of P. Falciparum Parasitemia Following Sporozoite Challenge
timeFrame: From day of challenge (Day 0) up to 159 days post-challenge
measure: Anti-circumsporozoite Protein (Anti-CS) Antibody Titers
timeFrame: 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)
measure: Anti-hepatitis B (Anti-HBs) Antibody Titers
timeFrame: 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)
measure: Anti-Adenovirus Type 35 (Ad35) Neutralizing Antibody Titers at Specified Time Points
timeFrame: 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)
measure: Frequency of CS (Total CS or Repeat)-Specific CD4+ T-cells
timeFrame: 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)
measure: Frequency of CS (Total CS or Repeat)-Specific CD8+ T Cells
timeFrame: 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)
measure: Frequency of HBs-specific CD4+ T-cells
timeFrame: 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)
measure: Frequency of CS-specific T-cells Producing IFN-γ
timeFrame: 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)
measure: Frequency of CS-specific T-cells Producing IFN-γ
timeFrame: 14 days post-dose 1 (Day 14)
Other outcomes:
Locations:
city: Silver Spring
country: United States
facility: GSK Investigational Site
state: Maryland
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.