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

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:
NCT01556945
First received: March 14, 2012
Last updated: May 1, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Malaria, Falciparum
Biological: FMP1/AS02
Biological: RTS,S/AS02
Other: AS02 adjuvant alone
Other: Malaria challenge
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Phase I/IIa Safety, Immunogenicity, and Preliminary Efficacy of an Administration Schedule of FMP1 and SmithKlineBeecham Biologicals' Candidate Malaria Vaccine RTS,S Each Adjuvanted With SBAS2, Given Concomitantly in Separate Injections

Resource links provided by NLM:


Further study details as provided by U.S. Army Medical Research and Materiel Command:

Primary Outcome Measures:
  • Safety [ Time Frame: two years ] [ Designated as safety issue: Yes ]
    Measured through adverse event collection and immunogenicity results


Enrollment: 72
Study Start Date: April 2001
Primary Completion Date: February 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A : FMP1/AS02 + RTS,S/AS02
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.
Biological: FMP1/AS02
The vaccine antigen FMP1 consists of a recombinant histidine-tagged (His6) fusion protein expressed in E. coli. The lyophilized pellet contained per vaccine vial 62.5 μg merozoite surface protein-142 (MSP-142) with 3.1% lactose as cryoprotectant in each 3 ml monodose vial. The pellet was reconstituted with AS02.
Biological: RTS,S/AS02
The vaccine antigen RTS,S, is a recombinant subunit vaccine produced in, and purified from yeast cells. The final lyophilized pellet contained 62.5 μg RTS,S with 3.15% lactose as cryoprotectant per 3 ml monodose vial. The pellet was reconstituted in AS02 and each 0.5 ml dose contained 50 μg RTS,S.
Other: Malaria challenge
Experimental challenge homologous strain of P.falciparum sporozoites. Mosquitoes infected with malaria approximately 17 to 19 days earlier and that contained sporozoites in their salivary glands. For each volunteer, five mosquitoes were allowed to feed over five minutes, after which they were dissected to confirm how many were infected, and the salivary glands scored.
Experimental: Group B : FMP1/AS02 + RTS,S/AS02
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.
Biological: FMP1/AS02
The vaccine antigen FMP1 consists of a recombinant histidine-tagged (His6) fusion protein expressed in E. coli. The lyophilized pellet contained per vaccine vial 62.5 μg merozoite surface protein-142 (MSP-142) with 3.1% lactose as cryoprotectant in each 3 ml monodose vial. The pellet was reconstituted with AS02.
Biological: RTS,S/AS02
The vaccine antigen RTS,S, is a recombinant subunit vaccine produced in, and purified from yeast cells. The final lyophilized pellet contained 62.5 μg RTS,S with 3.15% lactose as cryoprotectant per 3 ml monodose vial. The pellet was reconstituted in AS02 and each 0.5 ml dose contained 50 μg RTS,S.
Other: Malaria challenge
Experimental challenge homologous strain of P.falciparum sporozoites. Mosquitoes infected with malaria approximately 17 to 19 days earlier and that contained sporozoites in their salivary glands. For each volunteer, five mosquitoes were allowed to feed over five minutes, after which they were dissected to confirm how many were infected, and the salivary glands scored.
Experimental: Group C: FMP1/AS02 + AS02
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.
Biological: FMP1/AS02
The vaccine antigen FMP1 consists of a recombinant histidine-tagged (His6) fusion protein expressed in E. coli. The lyophilized pellet contained per vaccine vial 62.5 μg merozoite surface protein-142 (MSP-142) with 3.1% lactose as cryoprotectant in each 3 ml monodose vial. The pellet was reconstituted with AS02.
Other: AS02 adjuvant alone
AS02 adjuvant contains 50 μg monophosphoryl lipid A (MPL) and 50 μg Quillaja saponaria 21 (QS-21), 250 μl of SB62 (oil/water emulsion) in phosphate buffered saline (PBS) per volume of 0.5 ml.
Other: Malaria challenge
Experimental challenge homologous strain of P.falciparum sporozoites. Mosquitoes infected with malaria approximately 17 to 19 days earlier and that contained sporozoites in their salivary glands. For each volunteer, five mosquitoes were allowed to feed over five minutes, after which they were dissected to confirm how many were infected, and the salivary glands scored.
Experimental: Group D : RTS,S/AS02 + AS02
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.
Biological: RTS,S/AS02
The vaccine antigen RTS,S, is a recombinant subunit vaccine produced in, and purified from yeast cells. The final lyophilized pellet contained 62.5 μg RTS,S with 3.15% lactose as cryoprotectant per 3 ml monodose vial. The pellet was reconstituted in AS02 and each 0.5 ml dose contained 50 μg RTS,S.
Other: AS02 adjuvant alone
AS02 adjuvant contains 50 μg monophosphoryl lipid A (MPL) and 50 μg Quillaja saponaria 21 (QS-21), 250 μl of SB62 (oil/water emulsion) in phosphate buffered saline (PBS) per volume of 0.5 ml.
Other: Malaria challenge
Experimental challenge homologous strain of P.falciparum sporozoites. Mosquitoes infected with malaria approximately 17 to 19 days earlier and that contained sporozoites in their salivary glands. For each volunteer, five mosquitoes were allowed to feed over five minutes, after which they were dissected to confirm how many were infected, and the salivary glands scored.
Placebo Comparator: Control cohort
Infectivity controls (unvaccinated). Non-randomized infectivity controls were recruited specifically for the malaria challenge phase of the trial.
Other: Malaria challenge
Experimental challenge homologous strain of P.falciparum sporozoites. Mosquitoes infected with malaria approximately 17 to 19 days earlier and that contained sporozoites in their salivary glands. For each volunteer, five mosquitoes were allowed to feed over five minutes, after which they were dissected to confirm how many were infected, and the salivary glands scored.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  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: NCT01556945

Locations
United States, Maryland
WRAIR Clinical Trials Center
Silver Spring, Maryland, United States, 20910
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
GlaxoSmithKline
  More Information

No publications provided

Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT01556945     History of Changes
Other Study ID Numbers: WRAIR #849
Study First Received: March 14, 2012
Last Updated: May 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by U.S. Army Medical Research and Materiel Command:
P. falciparum
vaccine
healthy volunteers

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on July 20, 2014