Safety and Preliminary Efficacy of the Malaria Vaccine Candidates Falciparum Merozoite Protein-1 (FMP1) and SmithKlineBeecham (SKBB) Candidate Malaria Vaccine RTS,S (MAL019)

United States Army Medical Research and Development Command (USAMRDC)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Malaria, Falciparum

Treatments: Other: Malaria challenge; Biological: RTS,S/AS02; Other: AS02 adjuvant alone; Biological: FMP1/AS02

Study type: Interventional

Funder types: Other U.S. Federal agency; Industry

Identifiers

NCT01556945

WRAIR #849

Details and patient eligibility

About

The purpose of this study is to see if two new malaria vaccines called FMP1 and RTSS, combined with an adjuvant (called SBAS2) which helps stimulate the body's immune system, are safe, demonstrate an immune response through blood tests, and lastly, to see if the vaccines can prevent malaria infection.

The RTS,S vaccine contains a malaria protein in combination with a portion of the commercially available hepatitis B vaccine. The FMP1 vaccine also contains a malaria protein. The adjuvant called SBAS2, is a special oil in water emulsion. Vaccinations are done at study days 0, 28 and 84, followed by a malaria challenge approximately 14 days after the 3rd vaccination.

Enrollment: 72 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy adult, 18-45
• Available for duration of study (9 months)
• Written informed consent prior to any study procedures

Exclusion criteria

• Prior receipt of an investigational malaria vaccine or one containing MPL or QS-21
• Use of any investigational or non-registered drug/vaccine or planned administration of vaccine not foreseen by study protocol; each issue within 30 days preceding the first dose of study vaccine
• Administration of chronic immunosuppressants
• Chronic use of antibiotics
• History of malaria ever, or use of malaria chemoprophylaxis within 60 days prior to vaccination
• Known exposure to malaria within the past 12 months or planned travel to malarious area during the study period
• Confirmed or suspected immunosuppressive or immunodeficient condition
• Family history of congenital or hereditary immunodeficiency
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine
• Chronic or active neurologic disease including seizures
• History of splenectomy
• Seropositive for hepatitis B or hepatitis C or Human Immunodeficiency Virus (HIV), or other abnormal labs such as significant anemia, elevated creatinine
• Hepatomegaly, or right upper quadrant abdominal pain
• Pregnant or lactating female
• Chronic or active drug or alcohol use
• History of severe reactions to mosquito bites
• Any history of anaphylaxis to vaccinations

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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72 participants in 5 patient groups, including a placebo group

Group A : FMP1/AS02 + RTS,S/AS02

Experimental group

Description:

FMP1 malaria vaccine given with the GlaxoSmithKline (GSK) adjuvant system, number 2 (AS02) and a second experimental malaria vaccine RTS,S also given with AS02 adjuvant concomitantly as separate sites of injection on days 0, 28 and 84. Malaria challenge phase began 14-30 days after the last vaccine.

Treatment:

Biological: RTS,S/AS02

Biological: FMP1/AS02

Other: Malaria challenge

Group B : FMP1/AS02 + RTS,S/AS02

Experimental group

Description:

FMP1 malaria vaccine given with the adjuvant AS02 and a second experimental malaria vaccine RTS,S also given with AS02 adjuvant at one injection site and saline at the opposite site on days 0, 28 and 84. Malaria challenge phase began 14-30 days after the last vaccine.

Treatment:

Biological: RTS,S/AS02

Biological: FMP1/AS02

Other: Malaria challenge

Group C: FMP1/AS02 + AS02

Experimental group

Description:

FMP1 malaria vaccine given with the adjuvant AS02 and a second experimental malaria vaccine RTS,S also given with adjuvant AS02 adjuvant alone at one injection site and saline at the opposite site on days 0, 28 and 84. Malaria challenge phase began 14-30 days after the last vaccine.

Treatment:

Other: AS02 adjuvant alone

Biological: FMP1/AS02

Other: Malaria challenge

Group D : RTS,S/AS02 + AS02

Experimental group

Description:

RTS,S malaria vaccine given with the adjuvant AS02 and an adjuvant AS02 alone concomitantly at separate sites of injection on days 0, 28 and 84. Malaria challenge phase began 14-30 days after the last vaccine.

Treatment:

Other: AS02 adjuvant alone

Biological: RTS,S/AS02

Other: Malaria challenge

Control cohort

Placebo Comparator group

Description:

Infectivity controls (unvaccinated). Non-randomized infectivity controls were recruited specifically for the malaria challenge phase of the trial.

Treatment:

Other: Malaria challenge