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

This study has been completed.
Sponsor:
Collaborators:
The PATH Malaria Vaccine Initiative (MVI)
Crucell Holland BV
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01366534
First received: June 2, 2011
Last updated: June 20, 2013
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Malaria Vaccines
Biological: Crucell's replication deficient adenovirus type 35 circumsporozoite malaria vaccine (Ad35.CS.01)
Biological: GSK Biologicals' malaria vaccine 257049 (2 doses)
Biological: GSK Biologicals' malaria vaccine 257049 (3 doses)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Occurrence of P. falciparum parasitemia, defined by a positive blood slide [ Time Frame: From baseline (day of challenge) up to 159 days post-challenge ] [ Designated as safety issue: No ]
  • Occurrence of each solicited adverse event [ Time Frame: After each vaccine administration, over a 7-day follow-up period (day of vaccination and 6 subsequent days) ] [ Designated as safety issue: No ]
  • Occurrence of unsolicited adverse events after vaccination [ Time Frame: After each vaccine administration, over a 30-day follow-up period (day of vaccination and 29 subsequent days) ] [ Designated as safety issue: No ]
  • Occurrence of unsolicited adverse events after challenge [ Time Frame: After challenge, over a 30-day follow-up period (day of challenge and 29 subsequent days) ] [ Designated as safety issue: No ]
  • Occurrence of serious adverse events (SAEs) within 30 days after each vaccination [ Time Frame: After each vaccine administration, over a 30-day follow-up period (day of vaccination and 29 subsequent days) ] [ Designated as safety issue: No ]
  • Occurrence of SAEs during the whole study period [ Time Frame: From the time of first vaccination up to 236 days post-dose 1 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to P. falciparum parasitemia, defined by a positive blood slide [ Time Frame: From baseline (day of challenge) up to 159 days post-challenge ] [ Designated as safety issue: No ]
  • Anti- circumsporozoite protein (anti-CS) (repeat) and anti-hepatitis B (anti-HBs) antibody titres [ Time Frame: 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) ] [ Designated as safety issue: No ]
  • Anti-adenovirus type 35 (anti-Ad35) neutralizing antibody titers [ Time Frame: 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) ] [ Designated as safety issue: No ]
  • Frequency of CS (total CS or repeat)-specific T cells [ Time Frame: 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) ] [ Designated as safety issue: No ]
  • Frequency of HBs-specific T cells [ Time Frame: 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) ] [ Designated as safety issue: No ]

Enrollment: 68
Study Start Date: August 2011
Study Completion Date: July 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
Volunteers enrolled to this group will receive 1 dose of Ad35.CS.01 vaccine followed by 2 doses of the malaria 257049 vaccine
Biological: Crucell's replication deficient adenovirus type 35 circumsporozoite malaria vaccine (Ad35.CS.01)
One dose will be administered intramuscularly at Study Day 0.
Biological: GSK Biologicals' malaria vaccine 257049 (2 doses)
Two doses will be administered intramuscularly at monthly intervals
Active Comparator: Group B
Volunteers enrolled to this group will receive 3 doses of the investigational malaria 257049 vaccine
Biological: GSK Biologicals' malaria vaccine 257049 (3 doses)
Three doses will be administered intramuscularly at monthly intervals

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

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01366534

Locations
United States, Maryland
GSK Investigational Site
Silver Springs, Maryland, United States, 20910
Sponsors and Collaborators
GlaxoSmithKline
The PATH Malaria Vaccine Initiative (MVI)
Crucell Holland BV
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01366534     History of Changes
Other Study ID Numbers: 114460
Study First Received: June 2, 2011
Last Updated: June 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
safety
Vaccine
Phase 1/2
immunogenicity
Malaria
efficacy
sporozoite challenge

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on September 15, 2014