Clinical trial NCT00197054: Safety, Immunogenicity of RTS,S/AS02A, and RTS,S/AS01B Malaria Vaccines in Malaria-experienced Adults.
Official 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Plasmodium Falciparum
Lead sponsor: U.S. Army Medical Research and Development Command
Sponsor class: FED
Collaborators: name: GlaxoSmithKline
name: Walter Reed Army Institute of Research (WRAIR)
First posted: 2005-09-20
Enrollment: 255
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety: Proportion of Subjects With Grade 3 Solicited and Unsolicited General Reactions After Vaccination of RTS, S/AS02A and RTS, S/AS01B
timeFrame: 7 day follow-up (day of vaccination + 6 days)
measure: Safety: Number of Administered Doses Eliciting Grade 3 Unsolicited Symptoms
timeFrame: 6.5 months
measure: Safety: Number of Doses Eliciting Solicited Local Symptoms Reported Over 7 Day Follow-up Period
timeFrame: 7 day follow-up period (day of vaccination + 6 days)
Secondary outcomes:
measure: Safety: Occurrence of SAEs
timeFrame: months 6.5 thru 12
measure: Safety: Occurrence of SAEs
timeFrame: months 0 thru 12
measure: Occurrence of Hematology Parameters Below Normal Range
timeFrame: Days 0, 6, 66, and 90; Months 6 and 12
measure: Occurrence of Biochemistry Parameters Above Normal Ranges
timeFrame: Days 0, 6, and 90
Other outcomes:
measure: Seropositivity Rates for Anti-HBs Antibodies by Infection Status PRE
timeFrame: Prevaccination
measure: Seropositivity Rates for Anti-HBs Antibodies by Infection Status PIII(D90)
timeFrame: Day 90
measure: Seropositivity Rates for Anti-HBs Antibodies by Infection Status PIII(M12)
timeFrame: Month 12
measure: Seropositivity Rates for Anti-HBs Antibodies by Vaccine Group PRE
timeFrame: Prevaccination
measure: Seropositivity Rates for Anti-HBs Antibodies by Vaccine Group PIII(D90)
timeFrame: Day 90
measure: Seropositivity Rates for Anti-HBs Antibodies by Vaccine Group PIII(M12)
timeFrame: Month 12
measure: Seroprotection Rates for Anti-HBs Antibodies by Vaccine Group PRE
timeFrame: Prevaccination
measure: Seroprotection Rates for Anti-HBs Antibodies by Vaccine Group PIII (D90)
timeFrame: Day 90
measure: Seroprotection Rates for Anti-HBs Antibodies by Vaccine Group PIII (M12)
timeFrame: Month 12
measure: Geometric Mean Antibody Titers (GMTs) for Anti-HBs Antibodies by Vaccine Group PRE
timeFrame: Prevaccination
measure: Geometric Mean Titers (GMTs) for Anti-HBs Antibodies by Vaccine Group PIII (D90)
timeFrame: Day 90
measure: Geometric Mean Titers (GMTs) for Anti-HBs Antibodies by Vaccine Group PIII (M12)
timeFrame: Month 12
measure: Geometric Mean Titers (GMTs) for Anti-HBs Antibodies by Infection Status PRE
timeFrame: Prevaccination
measure: Geometric Mean Titers (GMTs) for Anti-HBs Antibodies by Infection Status PIII (D90)
timeFrame: Day 90
measure: Geometric Mean Titers (GMTs) for Anti-HBs Antibodies by Infection Status PIII (M12)
timeFrame: Month 12
measure: Geometric Mean Titers (GMTs) for Anti-CS Antibodies up to Month 12 by Vaccine Group PRE
timeFrame: Prevaccination
measure: Geometric Mean Titers (GMTs) for Anti-CS Antibodies up to Month 12 by Vaccine Group PII (D60)
timeFrame: 1 month post dose 2
measure: Geometric Mean Titers (GMTs) for Anti-CS Antibodies up to Month 12 by Vaccine Group PIII (D90)
timeFrame: 1 month post dose 3
measure: Geometric Mean Titers (GMTs) for Anti-CS Antibodies up to Month 12 by Vaccine Group PIII (M6.5)
timeFrame: 4 months post dose 3
measure: Geometric Mean Titers (GMTs) for Anti-CS Antibodies up to Month 12 by Vaccine Group PIII (M12)
timeFrame: 10 months post dose 3
measure: Geometric Mean Antibody Titers (GMTs) for Anti-CS Antibodies by Infection Status PRE
timeFrame: PRE
measure: Geometric Mean Antibody Titers (GMTs) for Anti-CS Antibodies by Infection Status PII (D60)
timeFrame: post dose 2 (day 60)
measure: Geometric Mean Antibody Titers (GMTs) for Anti-CS Antibodies by Infection Status PIII (D90)
timeFrame: post dose 3 (day 90)
measure: Geometric Mean Antibody Titers (GMTs) for Anti-CS Antibodies by Infection Status PIII (M6.5)
timeFrame: post dose 3 (month 6.5)
measure: Seropositivity Rates for Anti-CS Antibodies by Vaccine Group PRE
timeFrame: Prevaccination
measure: Seropositivity Rates for Anti-CS Antibodies by Vaccine Group PII (D60)
timeFrame: 1 month post dose 2
measure: Seropositivity Rates for Anti-CS Antibodies by Vaccine Group PIII (D90)
timeFrame: 1 month post dose 3
measure: Seropositivity Rates for Anti-CS Antibodies by Vaccine Group PIII (M6.5)
timeFrame: 4 months post dose 3
measure: Seropositivity Rates for Anti-CS Antibodies by Vaccine Group PIII (M12)
timeFrame: 10 months post dose 3
measure: Seropositivity Rates for Anti-CS Antibodies by Infection Status PRE
timeFrame: Prevaccination
measure: Seropositivity Rates for Anti-CS Antibodies by Infection Status PII (D60)
timeFrame: post dose 2 (day 60)
measure: Seropositivity Rates for Anti-CS Antibodies by Infection Status PIII (D90)
timeFrame: post dose 3 (day 90)
measure: Seropositivity Rates for Anti-CS Antibodies by Infection Status PIII (M6.5)
timeFrame: post dose 3 (month 6.5)
measure: Efficacy: Vaccine Efficacy Against P. Falciparum Infection
timeFrame: 14 days after dose 3 and extending for 14 weeks
measure: Percentage of Participants With Positive and Negative Parasite Density
timeFrame: at month 6.5
measure: Geometric Mean Antibody Titers (GMTs) of Asexual P. Falciparum Parasitemia
timeFrame: Month 6.5
Locations:
city: Kisumu
country: Kenya
facility: U.S. Army Research Unit-Kenya
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Polhemus ME, Remich SA, Ogutu BR, Waitumbi JN, Otieno L, Apollo S, Cummings JF, Kester KE, Ockenhouse CF, Stewart A, Ofori-Anyinam O, Ramboer I, Cahill CP, Lievens M, Dubois MC, Demoitie MA, Leach A, Cohen J, Ballou WR, Heppner DG Jr. Evaluation of RTS,S/AS02A and RTS,S/AS01B in adults in a high malaria transmission area. PLoS One. 2009 Jul 31;4(7):e6465. doi: 10.1371/journal.pone.0006465.