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

NCT00223990 | Completed Phase 2 Results

• 3 other identifiers: A-13228IND 92021123
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

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).

Conditions

Malaria, Falciparum

Keywords

Plasmodium; falciparum; malaria; vaccine; AS02A adjuvant; FMP1; Merozoite surface protein-1

Outcome Measures

Primary Outcomes (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

  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

  starting 14 days after the 3rd vaccination (day 71), every 28 days and ending on day 240

Secondary Outcomes (8)

• 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

  starting 14 days after the 3rd vaccination (day 71), every 28 days and ending on day 240

• Vaccine-Related Solicited Symptoms During 7-day Follow-up Period by Immunization - Intent to Treat (ITT) Population

  vaccination day plus post-vaccination days 1, 2, 3, and 6

• Vaccine-Related Solicited Symptoms During 7-day Follow-up Period by Immunization - According to Protocol (ATP) Population

  vaccination day plus post-vaccination days 1, 2, 3, and 6

• Vaccine-Related Unsolicited Adverse Events by Immunization - Intent to Treat (ITT) Population

  vaccination day and 29 subsequent days

• Vaccine-Related Unsolicited Adverse Events by Immunization - According to Protocol (ATP) Population

  vaccination day and 29 subsequent days

Study Arms (2)

FMP1/AS02A

EXPERIMENTAL

FMP1/AS02A candidate malaria vaccine was administered IM in the left anterolateral thigh muscle at 0, 1, and 2 months

Biological: FMP1/AS02A

RabAvert (rabies vaccine)

ACTIVE COMPARATOR

RabAvert vaccine was administered IM in the left anterolateral thigh muscle at 0, 1, and 2 months

Biological: RabAvert

Interventions

FMP1/AS02A BIOLOGICAL

FMP1/AS02A candidate malaria vaccine

FMP1/AS02A

RabAvert BIOLOGICAL

RabAvert rabies vaccine

RabAvert (rabies vaccine)

Eligibility Criteria

• Age: 12 Months - 47 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• The PATH Malaria Vaccine Initiative (MVI): collaborator
• United States Agency for International Development (USAID): collaborator
• GlaxoSmithKline: collaborator
• Kenya Medical Research Institute: collaborator
• Walter Reed Army Institute of Research (WRAIR): collaborator

Study Sites (1)

Walter Reed Project, Kombewa Clinic

Kisumu, Nyanza Province, Kenya

Location

Related Publications (3)

• Pichyangkul S, Gettayacamin M, Miller RS, Lyon JA, Angov E, Tongtawe P, Ruble DL, Heppner DG Jr, Kester KE, Ballou WR, Diggs CL, Voss G, Cohen JD, Walsh DS. Pre-clinical evaluation of the malaria vaccine candidate P. falciparum MSP1(42) formulated with novel adjuvants or with alum. Vaccine. 2004 Sep 28;22(29-30):3831-40. doi: 10.1016/j.vaccine.2004.07.023.

  PMID: 15364429 BACKGROUND

• Angov E, Aufiero BM, Turgeon AM, Van Handenhove M, Ockenhouse CF, Kester KE, Walsh DS, McBride JS, Dubois MC, Cohen J, Haynes JD, Eckels KH, Heppner DG, Ballou WR, Diggs CL, Lyon JA. Development and pre-clinical analysis of a Plasmodium falciparum Merozoite Surface Protein-1(42) malaria vaccine. Mol Biochem Parasitol. 2003 May;128(2):195-204. doi: 10.1016/s0166-6851(03)00077-x.

  PMID: 12742586 BACKGROUND

• Ogutu BR, Apollo OJ, McKinney D, Okoth W, Siangla J, Dubovsky F, Tucker K, Waitumbi JN, Diggs C, Wittes J, Malkin E, Leach A, Soisson LA, Milman JB, Otieno L, Holland CA, Polhemus M, Remich SA, Ockenhouse CF, Cohen J, Ballou WR, Martin SK, Angov E, Stewart VA, Lyon JA, Heppner DG, Withers MR; MSP-1 Malaria Vaccine Working Group. Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya. PLoS One. 2009;4(3):e4708. doi: 10.1371/journal.pone.0004708. Epub 2009 Mar 5.

  PMID: 19262754 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Results Point of Contact

• Title: Bernhards R. Ogutu, PhD
• Organization: Kenya Medical Research Institute

bogutu@kisian.mimcom.net

254-57-22942

Study Officials

• Bernhards Ogutu, M.D.

  Kenya Medical Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: 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)).

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 22, 2005
• Study Start: April 8, 2005
• Primary Completion: April 26, 2006
• Study Completion: June 1, 2007
• Last Updated: February 12, 2021
• Results First Posted: May 21, 2020

Record last verified: 2021-02

Locations

KE (1)