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Completed

NCT Number: NCT00197054

Safety, Immunogenicity of RTS,S/AS02A, and RTS,S/AS01B Malaria Vaccines in Malaria-experienced Adults.

The candidate malaria vaccine RTS,S/AS02A developed by GSK Biologicals demonstrated 30% efficacy against clinical episodes of malaria and approximately 58% efficacy against severe malaria disease. As a potential improvement to RTS,S/AS02A, another candidate vaccine RTS,S/AS01B is being developed in parallel in collaboration with the Walter Reed Army Institute of Research (WRAIR). This study will be the first administration of the RTS,S/AS01B vaccine to the African adults to establish safety and immunogenicity in this population. Preliminary indication of vaccine efficacy with this adjuvant will be established by monitoring the time to the first infection with Plasmodium falciparum.

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Key information

Conditions

Plasmodium Falciparum Infections Malaria Malaria, Falciparum Mosquito-Borne Diseases Parasitic Diseases Protozoan Infections Vector Borne Diseases

Age range

18 year–35 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

U.S. Army Research Unit-Kenya

Kisumu, Kenya

About this study

The study comprises of 3 groups and the participating subjects will be randomly allocated to one of the three groups. The first group will receive RTS,S/AS01B, the second group will receive RTS,S/AS02A and the third group will receive rabies vaccine. Immunization will be given by IM injection on 0, 1, 2 month schedule. Infants will be followed up daily for 7 days for solicited symptoms and 30 days for unsolicited symptoms after each vaccine dose. Serious adverse events will be recorded throughout the study period. A week prior to Dose 3, subjects will be treated with a licenced anti-malarial drug. Starting from two weeks after Dose 3, the subjects will be monitored for a 14-week duration for detection of malaria infection.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy male or female volunteers aged between 18 and 35 years at the time of first vaccination who have given written consent for their participation in the study were included
  • If the volunteer is female, she must be of non-childbearing potential, i.e. either surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series

Exclusion criteria

  • If a subject plans to take vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine(s) with the exception of tetanus toxoid will be excluded
  • Volunteers with any confirmed or suspected immunosuppressive or immunodeficient conditions
  • Family history of congenital or hereditary immunodeficiency
  • History of allergic reactions to previous immunizations
  • HBsAg positive subjects
  • History of splenectomy
  • Pregnant or lactating females will be excluded from the study

Treatment and study plan

RTS, S/AS01B

Biological

0.5mL dose; 50ug RTS, S antigen, 50ug QS21 and liposomes in phosphate-buffered saline administered intramuscular deltoid of non-dominant arm at 0, 1 and 2 months.

RTS, S/AS02A

Biological

0.5mL dose; 50ug RTS, S antigen, 50ug QS21 and proprietary oil-water emulsion in phosphate-buffered saline administered intramuscular deltoid of non-dominant arm at 0, 1 and 2 months.

Rabipur (Rabies) Vaccine

Biological

1.0mL dose administered intramuscular deltoid of non-dominant arm at 0, 1 and 2 months

Primary outcomes

  1. Safety: Proportion of Subjects With Grade 3 Solicited and Unsolicited General Reactions After Vaccination of RTS, S/AS02A and RTS, S/AS01B

    Time frame: 7 day follow-up (day of vaccination + 6 days)

    Proportion of subjects with grade 3 solicited and unsolicited general reactions after vaccination of RTS, S/AS02A and RTS, S/AS01B during a 7 day follow-up period (day of vaccination + 6 days).

  2. Safety: Number of Administered Doses Eliciting Grade 3 Unsolicited Symptoms

    Time frame: 6.5 months

    Grade 3 unsolicited symptoms reported following any number of administered doses

  3. Safety: Number of Doses Eliciting Solicited Local Symptoms Reported Over 7 Day Follow-up Period

    Time frame: 7 day follow-up period (day of vaccination + 6 days)

    Incidence overall solicited general and local reactions over 7 day follow-up period after dose 1, 2 and 3 (Total Cohort)

Secondary outcomes

  1. Safety: Occurrence of SAEs

    Time frame: months 6.5 thru 12

    Percentage of subjects experiencing SAEs classified by MedRA System Organ Class and Preferred Term (Month 6.5-12)

  2. Safety: Occurrence of SAEs

    Time frame: months 0 thru 12

    Percentage of subjects reporting SAEs classified by MedDRA System Organ Class and Preferred Term (Month 0-12)

  3. Occurrence of Hematology Parameters Below Normal Range

    Time frame: Days 0, 6, 66, and 90; Months 6 and 12

    Occurrence of hematology parameters below normal range (Total Cohort)

  4. Occurrence of Biochemistry Parameters Above Normal Ranges

    Time frame: Days 0, 6, and 90

    Occurrence of parameters of biochemical monitoring above normal ranges (Total Cohort)

Other outcomes

  1. Seropositivity Rates for Anti-HBs Antibodies by Infection Status PRE

    Time frame: Prevaccination

    Seropositivity rates and GMTs for Anti-HBs antibodies by infection status (Total Cohort) Seropositive >3.3 mlU/mL; Seroprotected >10 mIU/mL Infection defined as P. falciparum asexual parasitemia >0 PRE= Prevaccination

  2. Seropositivity Rates for Anti-HBs Antibodies by Infection Status PIII(D90)

    Time frame: Day 90

    Seropositivity rates and GMTs for Anti-HBs antibodies by infection status (Total Cohort) Seropositive >3.3 mlU/mL; Seroprotected: >10 mlU/mL Infection defined as P. falciparum asexual parasitemia >0 PIII(D90)= post dose 3 (day 90)

  3. Seropositivity Rates for Anti-HBs Antibodies by Infection Status PIII(M12)

    Time frame: Month 12

    Seropositivity rates and GMTs for Anti-HBs antibodies by infection status (Total Cohort) Seropositive >3.3 mlU/mL; Seroprotected: >10 mlU/mL Infection defined as P. falciparum asexual parasitemia >0 PIII(M12)= post dose 3 (month 12)

  4. Seropositivity Rates for Anti-HBs Antibodies by Vaccine Group PRE

    Time frame: Prevaccination

    Seropositivity rates for Anti-HBs antibodies by vaccine group (ATP Cohort for Immunogenicity).

    Seropositive >3.3 mlU/ML

    PRE=Prevaccination

  5. Seropositivity Rates for Anti-HBs Antibodies by Vaccine Group PIII(D90)

    Time frame: Day 90

    Seropositivity rates for Anti-HBs antibodies by vaccine group (ATP Cohort for Immunogenicity).

    Seropositive >3.3 mlU/ML

    PIII(D90)= post dose 3 (Day 90)

  6. Seropositivity Rates for Anti-HBs Antibodies by Vaccine Group PIII(M12)

    Time frame: Month 12

    Seropositivity rates for Anti-HBs antibodies by vaccine group (ATP Cohort for Immunogenicity).

    Seropositive >3.3 mlU/ML

    PIII(M12)= post dose 3 (Month 12)

  7. Seroprotection Rates for Anti-HBs Antibodies by Vaccine Group PRE

    Time frame: Prevaccination

    Seroprotection rates for Anti-HBs antibodies by vaccine group (ATP Cohort for Immunogenicity).

    Seroprotected >10 mlU/mL

    PRE=Prevaccination

  8. Seroprotection Rates for Anti-HBs Antibodies by Vaccine Group PIII (D90)

    Time frame: Day 90

    Seroprotection rates for Anti-HBs antibodies by vaccine group (ATP Cohort for Immunogenicity).

    Seroprotected >10 mlU/mL

    PIII(D90)= post dose 3 (Day 90)

  9. Seroprotection Rates for Anti-HBs Antibodies by Vaccine Group PIII (M12)

    Time frame: Month 12

    Seroprotection rates for Anti-HBs antibodies by vaccine group (ATP Cohort for Immunogenicity).

    Seroprotected >10 mlU/mL

    PIII(M12)= post dose 3 (Month 12)

  10. Geometric Mean Antibody Titers (GMTs) for Anti-HBs Antibodies by Vaccine Group PRE

    Time frame: Prevaccination

    Geometric mean antibody titers (GMTs) for Anti-HBs antibodies by vaccine group (According to protocol (ATP) Cohort for Immunogenicity)

    PRE=Prevaccination

  11. Geometric Mean Titers (GMTs) for Anti-HBs Antibodies by Vaccine Group PIII (D90)

    Time frame: Day 90

    Geometric mean titers (GMTs) for Anti-HBs antibodies by vaccine group (According to protocol (ATP) Cohort for Immunogenicity)

    PIII(D90)= post dose 3 (Day 90)

  12. Geometric Mean Titers (GMTs) for Anti-HBs Antibodies by Vaccine Group PIII (M12)

    Time frame: Month 12

    Geometric mean titers (GMTs) for Anti-HBs antibodies by vaccine group (According to protocol (ATP) Cohort for Immunogenicity)

    PIII(M12)= post dose 3 (Month 12)

  13. Geometric Mean Titers (GMTs) for Anti-HBs Antibodies by Infection Status PRE

    Time frame: Prevaccination

    Geometric mean titers (GMTs) for Anti-HBs antibodies by infection status (Total Cohort) Infection defined as P. falciparum asexual parasitemia >0 PRE= Prevaccination

  14. Geometric Mean Titers (GMTs) for Anti-HBs Antibodies by Infection Status PIII (D90)

    Time frame: Day 90

    Geometric mean titers (GMTs) for Anti-HBs antibodies by infection status (Total Cohort) Infection defined as P. falciparum asexual parasitemia >0 PIII(D90)= post dose 3 (day 90)

  15. Geometric Mean Titers (GMTs) for Anti-HBs Antibodies by Infection Status PIII (M12)

    Time frame: Month 12

    Geometric mean titers (GMTs) for Anti-HBs antibodies by infection status (Total Cohort) Infection defined as P. falciparum asexual parasitemia >0 PIII(M12)= post dose 3 (month 12)

  16. Geometric Mean Titers (GMTs) for Anti-CS Antibodies up to Month 12 by Vaccine Group PRE

    Time frame: Prevaccination

    Geometric mean titers (GMTs) for Anti-CS antibodies accessed prevaccination, 1 month post dose 2, 1 month post dose 3, 4 months post dose 3 and 10 months post dose 3 PRE= prevaccination

  17. Geometric Mean Titers (GMTs) for Anti-CS Antibodies up to Month 12 by Vaccine Group PII (D60)

    Time frame: 1 month post dose 2

    Geometric mean titers (GMTs) for Anti-CS antibodies accessed prevaccination, 1 month post dose 2, 1 month post dose 3, 4 months post dose 3 and 10 months post dose 3 PII(D60)= post dose 2 (day 60)

  18. Geometric Mean Titers (GMTs) for Anti-CS Antibodies up to Month 12 by Vaccine Group PIII (D90)

    Time frame: 1 month post dose 3

    Geometric mean titers (GMTs) for Anti-CS antibodies accessed prevaccination, 1 month post dose 2, 1 month post dose 3, 4 months post dose 3 and 10 months post dose 3 PIII(D90)= post dose 3 (day 90)

  19. Geometric Mean Titers (GMTs) for Anti-CS Antibodies up to Month 12 by Vaccine Group PIII (M6.5)

    Time frame: 4 months post dose 3

    Geometric mean titers (GMTs) for Anti-CS antibodies accessed prevaccination, 1 month post dose 2, 1 month post dose 3, 4 months post dose 3 and 10 months post dose 3 PIII(M6.5)= post dose 3 (month 6.5)

  20. Geometric Mean Titers (GMTs) for Anti-CS Antibodies up to Month 12 by Vaccine Group PIII (M12)

    Time frame: 10 months post dose 3

    Geometric mean titers (GMTs) for Anti-CS antibodies accessed prevaccination, 1 month post dose 2, 1 month post dose 3, 4 months post dose 3 and 10 months post dose 3 PIII(M12)= post dose 3 (month 12)

  21. Geometric Mean Antibody Titers (GMTs) for Anti-CS Antibodies by Infection Status PRE

    Time frame: PRE

    Geometric mean antibody titers (GMTs) for Anti-CS antibodies by infection status on RTS,S/AS01B and RTS,S/AS02A recipients only Infection defined as P. falciparum asexual parasitemia >0 PRE= Pre-vaccination

  22. Geometric Mean Antibody Titers (GMTs) for Anti-CS Antibodies by Infection Status PII (D60)

    Time frame: post dose 2 (day 60)

    Geometric mean antibody titers (GMTs) for Anti-CS antibodies by infection status on RTS,S/AS01B and RTS,S/AS02A recipients only Infection defined as P. falciparum asexual parasitemia >0 PII(D60)= post dose 2 (day 60)

  23. Geometric Mean Antibody Titers (GMTs) for Anti-CS Antibodies by Infection Status PIII (D90)

    Time frame: post dose 3 (day 90)

    Geometric mean antibody titers (GMTs) for Anti-CS antibodies by infection status on RTS,S/AS01B and RTS,S/AS02A recipients only Infection defined as P. falciparum asexual parasitemia >0 PIII(D90)= post dose 3 (day 90)

  24. Geometric Mean Antibody Titers (GMTs) for Anti-CS Antibodies by Infection Status PIII (M6.5)

    Time frame: post dose 3 (month 6.5)

    Geometric mean antibody titers (GMTs) for Anti-CS antibodies by infection status on RTS,S/AS01B and RTS,S/AS02A recipients only Infection defined as P. falciparum asexual parasitemia >0 PIII(M6.5)= post dose 3 (month 6.5)

  25. Seropositivity Rates for Anti-CS Antibodies by Vaccine Group PRE

    Time frame: Prevaccination

    Seropositivity rates for Anti-CS antibodies accessed prevaccination, 1 month post dose 2, 1 month post dose 3, 4 months post dose 3 and 10 months post dose 3

    PRE= prevaccination

  26. Seropositivity Rates for Anti-CS Antibodies by Vaccine Group PII (D60)

    Time frame: 1 month post dose 2

    Seropositivity rates for Anti-CS antibodies accessed prevaccination, 1 month post dose 2, 1 month post dose 3, 4 months post dose 3 and 10 months post dose 3.

    PII(D60)= post dose 2 (day 60)

  27. Seropositivity Rates for Anti-CS Antibodies by Vaccine Group PIII (D90)

    Time frame: 1 month post dose 3

    Seropositivity rates for Anti-CS antibodies accessed prevaccination, 1 month post dose 2, 1 month post dose 3, 4 months post dose 3 and 10 months post dose 3

    PIII(D90)= post dose 3 (day 90)

  28. Seropositivity Rates for Anti-CS Antibodies by Vaccine Group PIII (M6.5)

    Time frame: 4 months post dose 3

    Seropositivity rates for Anti-CS antibodies accessed prevaccination, 1 month post dose 2, 1 month post dose 3, 4 months post dose 3 and 10 months post dose 3

    PIII(M6.5)= post dose 3 (month 6.5)

  29. Seropositivity Rates for Anti-CS Antibodies by Vaccine Group PIII (M12)

    Time frame: 10 months post dose 3

    Seropositivity rates for Anti-CS antibodies accessed prevaccination, 1 month post dose 2, 1 month post dose 3, 4 months post dose 3 and 10 months post dose 3

    PIII(M12)= post dose 3 (month 12)

  30. Seropositivity Rates for Anti-CS Antibodies by Infection Status PRE

    Time frame: Prevaccination

    Seropositivity rates for Anti-CS antibodies by infection status on RTS,S/AS01B and RTS,S/AS02A recipients only Seropositive: >0.5EU/mL Infection defined as P. falciparum asexual parasitemia >0 PRE= Pre-vaccination

  31. Seropositivity Rates for Anti-CS Antibodies by Infection Status PII (D60)

    Time frame: post dose 2 (day 60)

    Seropositivity rates for Anti-CS antibodies by infection status on RTS,S/AS01B and RTS,S/AS02A recipients only Seropositive: >0.5EU/mL Infection defined as P. falciparum asexual parasitemia >0 PII(D60)= post dose 2 (day 60)

  32. Seropositivity Rates for Anti-CS Antibodies by Infection Status PIII (D90)

    Time frame: post dose 3 (day 90)

    Seropositivity rates for Anti-CS antibodies by infection status on RTS,S/AS01B and RTS,S/AS02A recipients only Seropositive: >0.5EU/mL Infection defined as P. falciparum asexual parasitemia >0 PIII(D90)= post dose 3 (day 90)

  33. Seropositivity Rates for Anti-CS Antibodies by Infection Status PIII (M6.5)

    Time frame: post dose 3 (month 6.5)

    Seropositivity rates for Anti-CS antibodies by infection status on RTS,S/AS01B and RTS,S/AS02A recipients only Seropositive: >0.5EU/mL Infection defined as P. falciparum asexual parasitemia >0 PIII(M6.5)= post dose 3 (month 6.5)

  34. Efficacy: Vaccine Efficacy Against P. Falciparum Infection

    Time frame: 14 days after dose 3 and extending for 14 weeks

    Number of subjects with an episode of parasitemia (first recording of infection of asexual stage falciparum parasites >0 detected by active detection of infection (ADI) or passive case detection)

  35. Percentage of Participants With Positive and Negative Parasite Density

    Time frame: at month 6.5

    Percentage of participants with positive and negative parasite density at month 6.5

  36. Geometric Mean Antibody Titers (GMTs) of Asexual P. Falciparum Parasitemia

    Time frame: Month 6.5

    Geometric Mean Antibody Titers (GMTs) of Asexual P. falciparum parasitemia at Month 6.5

Sponsors and collaborators

Lead sponsor

U.S. Army Medical Research and Development Command

Fed

Collaborators

  • GlaxoSmithKline
  • Walter Reed Army Institute of Research (WRAIR)

Registry information

Official study title

A Phase IIb Randomized, Double-blind, Controlled Study of the Safety, Immunogenicity and Proof-of-concept of RTS,S/AS02A, and RTS,S/AS01B, Two Candidate Malaria Vaccines in Malaria-experienced Adults Living in Western Kenya.

Important dates

Study start
2005
Primary completion
2006
Study completion
2006
First posted
Sep 20, 2005
Registry last updated
Feb 12, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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