Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Double-blind, Randomized, Controlled Study of Safety, Immunogenicity and Efficacy of a Candidate Malaria Vaccine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00223990
Recruitment Status : Completed
First Posted : September 22, 2005
Results First Posted : May 21, 2020
Last Update Posted : May 21, 2020
Sponsor:
Collaborators:
The PATH Malaria Vaccine Initiative (MVI)
United States Agency for International Development (USAID)
GlaxoSmithKline
Kenya Medical Research Institute
Walter Reed Army Institute of Research (WRAIR)
Information provided by (Responsible Party):
U.S. Army Medical Research and Development Command

Brief Summary:

This trial is currently evaluating one candidate malaria vaccine, FMP1/AS02A. This candidate malaria vaccine is being developed for the routine immunization of infants and children living in malaria-endemic areas. This vaccine would offer protection against malaria disease due to the parasite Plasmodium falciparum.

Prior to the start of this study, FMP1/AS02A had been given to approximately 60 malaria-naïve adults and 40 adults and 90 children living in malaria-endemic regions.

This study will investigate whether the candidate vaccine prevents malaria disease for 6 months post-vaccination.

One half of the enrolled subjects will receive FMP1/AS02A and the other half rabies vaccine (RabAvert).


Condition or disease Intervention/treatment Phase
Malaria, Falciparum Biological: FMP1/AS02A Biological: RabAvert Phase 2

Detailed Description:

Field trial of a candidate antigen/adjuvant conducted at one study center with 12 outlying (satellite) field stations. Subjects were screened no more than 45 days prior to the first inoculation and were randomized on the first day of vaccination 1:1 between two arms (FMP1/AS02A and rabies vaccine). The planned immunization schedule was 0, 1, and 2 months for both study arms; however, the 4-week intervals between doses could be extended for up to 2 additional weeks if temporary suspension was deemed advisable due to serious adverse events (SAEs) or other concerns. Vaccinations were administered intramuscularly (IM) in the left anterolateral thigh muscle unless a compelling reason for using an alternate injection site was evident. Each subject participated in the study approximately 14 months with 7-day follow-up for solicited adverse events (five visits: vaccination day plus post-vaccination days 1, 2, 3, and 6) and 30-day follow-up for unsolicited events (vaccination day plus 29 subsequent days). Follow-up of SAEs continued for study duration. Active case detection occurred during the Efficacy Follow-up Period (169 days, starting 14 days after the third vaccination (Day 71)), active case detection commenced with visits approximately every 28 days to the Walter Reed Project Kombewa clinic and terminated after 6 months (approximately Day 240). The primary study analysis for all endpoints was completed on the cleaned Efficacy Follow-up Period database after a data-lock-point. The Addendum Efficacy Follow-up Period (125 days) started with the end of the Efficacy Follow-up Period (approximately Day 240) and active case detection commenced with visits approximately every 28 days to the Walter Reed Project Kombewa Clinic and terminated after 10 months (approximately Day 364). The study addendum analysis for all endpoints was completed after the Addendum Efficacy Follow-up Period database after a data-lock-point.

Malaria cases were detected actively and passively. Active case detection was handled through scheduled (1) facilitated participant visits to the Kombewa Clinic and (2) field worker visits to participant homes. Passive case detection was handled through unscheduled, self-presentation of participants to the Kombewa Clinic. At scheduled clinic visits, blood samples were taken from all subjects to determine parasite density and hemoglobin levels. At home visits, subjects with fever or other illness within the 24 hours were transported to the clinic for collection of blood samples.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects were screened no more than 45 days prior to the first inoculation and were randomized on the first day of vaccination 1:1 between two arms (FMP1/AS02A and rabies vaccine (RabAvert)).
Masking: Double (Participant, Investigator)
Masking Description: Both study participants and those investigators responsible for evaluation of the endpoints will be blinded as to who receives the test article versus the comparator. On vaccination days, the comparator vaccine will be in the same package as received from the manufacturer. After agitation it will appear clear and pink. The FMP1 antigen and the AS02A adjuvant will be packaged separately. The reconstituted FMPI antigen in the AS02A adjuvant/diluent will have a milky white appearance. Because the vaccines will have a markedly different appearance, contents of the syringe will be concealed as described later in this section. The two vaccine preparation teams, consisting of the study pharmacist, pharmacy assistants, and drug manager (an experienced nurse, clinician, or pharmacist), will be responsible for vaccine preparation. They will also verify that the proper vaccine and vaccine dose is prepared and delivered to each subject.
Primary Purpose: Prevention
Official Title: A Dbl-blind,Randomized,Controlled,Phase IIb Field Trial in 12-47 Month-old Children in Western Kenya to Eval the Efficacy,Safety and Immunogenicity of the FMP1/AS02A Malaria Vaccine vs Rabies Vaccine
Actual Study Start Date : April 8, 2005
Actual Primary Completion Date : April 26, 2006
Actual Study Completion Date : June 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria Rabies

Arm Intervention/treatment
Experimental: FMP1/AS02A
FMP1/AS02A candidate malaria vaccine was administered IM in the left anterolateral thigh muscle at 0, 1, and 2 months
Biological: FMP1/AS02A
FMP1/AS02A candidate malaria vaccine

Active Comparator: RabAvert (rabies vaccine)
RabAvert vaccine was administered IM in the left anterolateral thigh muscle at 0, 1, and 2 months
Biological: RabAvert
RabAvert rabies vaccine




Primary Outcome Measures :
  1. Subjects Time to First Clinical Episode of P Falciparum Malaria During the Efficacy Follow-up Period Adjusted for Time at Risk - Intent to Treat (ITT) Population [ Time Frame: starting 14 days after the 3rd vaccination (day 71), every 28 days and ending on day 240 ]

    Days to first clinical episode of P falciparum malaria during the efficacy f/u period for ITT population

    Time at Risk adjusted for:

    SA= study absence MT= malaria treatment SA MT= study absence and malaria treatment

    Case Definitions:

    Primary = >37.5°C with presence of a density of asexual stage P. falciparum >50K parasites/µL blood Secondary (200) = >37.5°C with presence of a density of asexual stage P. falciparum >200K parasites/µL blood Secondary (100) = >37.5°C with presence of a density of asexual stage P. falciparum >100K parasites/µL blood Secondary (10) = >37.5°C with presence of a density of asexual stage P. falciparum >10K parasites/µL blood Secondary (0) = >37.5°C with presence of a density of asexual stage P. falciparum >0 parasites/µL blood Secondary (0*) = >37.5°C OR history of fever in the last 24 hrs with presence of a density of asexual stage P. falciparum >0 parasites/µL blood



Secondary Outcome Measures :
  1. Time to First Clinical Episode of P Falciparum Malaria During the Efficacy Follow-up Period Adjusted for Time at Risk - According to Protocol (ATP) Population [ Time Frame: starting 14 days after the 3rd vaccination (day 71), every 28 days and ending on day 240 ]

    Days to first clinical episode of P falciparum malaria during the efficacy f/u period for ATP population

    Time at Risk adjusted for:

    SA= study absence MT= malaria treatment SA MT= study absence and malaria treatment

    Case Definitions:

    Primary = >37.5°C with presence of a density of asexual stage P. falciparum >50K parasites/µL blood Secondary (200) = >37.5°C with presence of a density of asexual stage P. falciparum >200K parasites/µL blood Secondary (100) = >37.5°C with presence of a density of asexual stage P. falciparum >100K parasites/µL blood Secondary (10) = >37.5°C with presence of a density of asexual stage P. falciparum >10K parasites/µL blood Secondary (0) = >37.5°C with presence of a density of asexual stage P. falciparum >0 parasites/µL blood Secondary (0*) = >37.5°C OR history of fever in the last 24 hrs with presence of a density of asexual stage P. falciparum >0 parasites/µL blood


  2. Vaccine-Related Solicited Symptoms During 7-day Follow-up Period by Immunization - Intent to Treat (ITT) Population [ Time Frame: vaccination day plus post-vaccination days 1, 2, 3, and 6 ]

    Each subject participated in the study approximately 14 months with 7-day follow-up for solicited adverse events (five visits: vaccination day plus post-vaccination days 1, 2, 3, and 6).

    I1 = Immunization 1 I2 = Immunization 2 I3 = Immunization 3


  3. Vaccine-Related Solicited Symptoms During 7-day Follow-up Period by Immunization - According to Protocol (ATP) Population [ Time Frame: vaccination day plus post-vaccination days 1, 2, 3, and 6 ]

    Each subject participated in the study approximately 14 months with 7-day follow-up for solicited adverse events (five visits: vaccination day plus post-vaccination days 1, 2, 3, and 6).

    I1 = Immunization 1 I2 = Immunization 2 I3 = Immunization 3


  4. Vaccine-Related Unsolicited Adverse Events by Immunization - Intent to Treat (ITT) Population [ Time Frame: vaccination day and 29 subsequent days ]

    Each subject participated in the study approximately 14 months with 7-day follow-up for solicited adverse events (five visits: vaccination day plus post-vaccination days 1, 2, 3, and 6) and 30-day follow-up for unsolicited events (vaccination day plus 29 subsequent days).

    I1 = Immunization 1 I2 = Immunization 2 I3 = Immunization 3


  5. Vaccine-Related Unsolicited Adverse Events by Immunization - According to Protocol (ATP) Population [ Time Frame: vaccination day and 29 subsequent days ]

    Each subject participated in the study approximately 14 months with 7-day follow-up for solicited adverse events (five visits: vaccination day plus post-vaccination days 1, 2, 3, and 6) and 30-day follow-up for unsolicited events (vaccination day plus 29 subsequent days).

    I1 = Immunization 1 I2 = Immunization 2 I3 = Immunization 3


  6. Number of Patients Who Showed Symptoms, Unsolicited Adverse Events, and Serious Adverse Events by Immunization [ Time Frame: vaccination day plus post-vaccine days 1, 2, 3, and 6; 30 day follow-up for unsolicited events and follow-up for SAEs to continue for duration of study (364 days) ]
    Each subject participated in the study approximately 14 months with 7-day follow-up for solicited adverse events (five visits: vaccination day plus post-vaccination days 1, 2, 3, and 6) and 30-day follow-up for unsolicited events (vaccination day plus 29 subsequent days). Follow-up of SAEs continued for study duration (364 days)

  7. Vaccine-Related Local and Systemic Solicited Adverse Events by Immunization - According to Protocol (ATP) [ Time Frame: vaccination day plus 29 subsequent days ]

    Each subject participated in the study approximately 14 months with 7-day follow-up for solicited adverse events (five visits: vaccination day plus post-vaccination days 1, 2, 3, and 6) and 30-day follow-up for unsolicited events (vaccination day plus 29 subsequent days).

    I1 = Immunization 1 I2 = Immunization 2 I3 = Immunization 3


  8. Vaccine-Related Local and Systemic Solicited Adverse Events by Immunization - Intent to Treat (ITT) [ Time Frame: vaccination day plus 29 subsequent days ]

    Each subject participated in the study approximately 14 months with 7-day follow-up for solicited adverse events (five visits: vaccination day plus post-vaccination days 1, 2, 3, and 6) and 30-day follow-up for unsolicited events (vaccination day plus 29 subsequent days).

    I1 = Immunization 1 I2 = Immunization 2 I3 = Immunization 3




Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Months to 47 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

All subjects must satisfy the following criteria at study entry:

  • A healthy male or female child, 12 to 47 months of age on the day of screening
  • Written informed consent obtained from at least one parent/guardian before study start
  • Available to participate for the study duration (about 14 months)

Exclusion Criteria:

  • Acute disease at the time of entry into the study that in the opinion of the investigator may pose a threat to the subject
  • Prior receipt of a rabies vaccine or any investigational vaccine
  • Use of any investigational drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use up to 30 days after the third dose
  • Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of vaccination. (For corticosteroids, this will mean prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed)
  • Administration or anticipated administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine(s) with the exception of tetanus toxoid
  • Previous vaccination with a vaccine containing MPL or QS21 (e.g., RTS,S/AS02A)
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection. (No HIV test will be performed as part of this study.)
  • History of allergic reactions or anaphylaxis to immunizations or to any vaccine components, such as eggs
  • History of surgical splenectomy
  • Administration of immunoglobulins, blood transfusions, or any other blood products within the six months preceding the first dose of study vaccine or planned administration during the study period
  • Simultaneous participation in any other clinical trial
  • Acute or chronic cardiovascular, pulmonary, hepatic, or renal condition that in the opinion of the PI, may increase the risk to the subject from participating in the study
  • Any other condition or circumstance that in the opinion of the investigator may pose a threat to the subject

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00223990


Locations
Layout table for location information
Kenya
Walter Reed Project
Kombewa Clinic, City Of Kisumu, Nyanza Province, Kenya
Sponsors and Collaborators
U.S. Army Medical Research and Development Command
The PATH Malaria Vaccine Initiative (MVI)
United States Agency for International Development (USAID)
GlaxoSmithKline
Kenya Medical Research Institute
Walter Reed Army Institute of Research (WRAIR)
Investigators
Layout table for investigator information
Principal Investigator: Bernhards Ogutu, M.D. Kenya Medical Research Institute
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: U.S. Army Medical Research and Development Command
ClinicalTrials.gov Identifier: NCT00223990    
Other Study ID Numbers: A-13228
IND 9202 ( Other Identifier: FDA )
1123 ( Other Identifier: WRAIR )
First Posted: September 22, 2005    Key Record Dates
Results First Posted: May 21, 2020
Last Update Posted: May 21, 2020
Last Verified: May 2020
Keywords provided by U.S. Army Medical Research and Development Command:
Plasmodium
falciparum
malaria
vaccine
AS02A adjuvant
FMP1
Merozoite surface protein-1
Additional relevant MeSH terms:
Layout table for MeSH terms
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases