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

Plasmodium Falciparum Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00197054
• Other study ID #: A-12227
• Secondary ID: IND 11220
• Status: Completed
• Phase: Phase 2
• Start date: July 2005
• Est. completion date: September 2006

Study information

• Verified date: February 2021
• Source: U.S. Army Medical Research and Development Command
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 255
• Est. completion date: September 2006
• Est. primary completion date: September 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Malaria
• Plasmodium Falciparum

Intervention

Biological:
• RTS, S/AS01B
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
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
1.0mL dose administered intramuscular deltoid of non-dominant arm at 0, 1 and 2 months

Locations

Country	Name	City	State
Kenya	U.S. Army Research Unit-Kenya	Kisumu

Sponsors (3)

Lead Sponsor	Collaborator
U.S. Army Medical Research and Development Command	GlaxoSmithKline, Walter Reed Army Institute of Research (WRAIR)

Country where clinical trial is conducted

Kenya, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Seropositivity Rates for Anti-HBs Antibodies by Infection Status PRE	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	Prevaccination
Other	Seropositivity Rates for Anti-HBs Antibodies by Infection Status PIII(D90)	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)	Day 90
Other	Seropositivity Rates for Anti-HBs Antibodies by Infection Status PIII(M12)	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)	Month 12
Other	Seropositivity Rates for Anti-HBs Antibodies by Vaccine Group PRE	Seropositivity rates for Anti-HBs antibodies by vaccine group (ATP Cohort for Immunogenicity).; Seropositive >3.3 mlU/ML; PRE=Prevaccination	Prevaccination
Other	Seropositivity Rates for Anti-HBs Antibodies by Vaccine Group PIII(D90)	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)	Day 90
Other	Seropositivity Rates for Anti-HBs Antibodies by Vaccine Group PIII(M12)	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)	Month 12
Other	Seroprotection Rates for Anti-HBs Antibodies by Vaccine Group PRE	Seroprotection rates for Anti-HBs antibodies by vaccine group (ATP Cohort for Immunogenicity).; Seroprotected >10 mlU/mL; PRE=Prevaccination	Prevaccination
Other	Seroprotection Rates for Anti-HBs Antibodies by Vaccine Group PIII (D90)	Seroprotection rates for Anti-HBs antibodies by vaccine group (ATP Cohort for Immunogenicity).; Seroprotected >10 mlU/mL; PIII(D90)= post dose 3 (Day 90)	Day 90
Other	Seroprotection Rates for Anti-HBs Antibodies by Vaccine Group PIII (M12)	Seroprotection rates for Anti-HBs antibodies by vaccine group (ATP Cohort for Immunogenicity).; Seroprotected >10 mlU/mL; PIII(M12)= post dose 3 (Month 12)	Month 12
Other	Geometric Mean Antibody Titers (GMTs) for Anti-HBs Antibodies by Vaccine Group PRE	Geometric mean antibody titers (GMTs) for Anti-HBs antibodies by vaccine group (According to protocol (ATP) Cohort for Immunogenicity); PRE=Prevaccination	Prevaccination
Other	Geometric Mean Titers (GMTs) for Anti-HBs Antibodies by Vaccine Group PIII (D90)	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)	Day 90
Other	Geometric Mean Titers (GMTs) for Anti-HBs Antibodies by Vaccine Group PIII (M12)	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)	Month 12
Other	Geometric Mean Titers (GMTs) for Anti-HBs Antibodies by Infection Status PRE	Geometric mean titers (GMTs) for Anti-HBs antibodies by infection status (Total Cohort) Infection defined as P. falciparum asexual parasitemia >0 PRE= Prevaccination	Prevaccination
Other	Geometric Mean Titers (GMTs) for Anti-HBs Antibodies by Infection Status PIII (D90)	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)	Day 90
Other	Geometric Mean Titers (GMTs) for Anti-HBs Antibodies by Infection Status PIII (M12)	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)	Month 12
Other	Geometric Mean Titers (GMTs) for Anti-CS Antibodies up to Month 12 by Vaccine Group PRE	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	Prevaccination
Other	Geometric Mean Titers (GMTs) for Anti-CS Antibodies up to Month 12 by Vaccine Group PII (D60)	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)	1 month post dose 2
Other	Geometric Mean Titers (GMTs) for Anti-CS Antibodies up to Month 12 by Vaccine Group PIII (D90)	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)	1 month post dose 3
Other	Geometric Mean Titers (GMTs) for Anti-CS Antibodies up to Month 12 by Vaccine Group PIII (M6.5)	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)	4 months post dose 3
Other	Geometric Mean Titers (GMTs) for Anti-CS Antibodies up to Month 12 by Vaccine Group PIII (M12)	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)	10 months post dose 3
Other	Geometric Mean Antibody Titers (GMTs) for Anti-CS Antibodies by Infection Status 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	PRE
Other	Geometric Mean Antibody Titers (GMTs) for Anti-CS Antibodies by Infection Status PII (D60)	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)	post dose 2 (day 60)
Other	Geometric Mean Antibody Titers (GMTs) for Anti-CS Antibodies by Infection Status PIII (D90)	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)	post dose 3 (day 90)
Other	Geometric Mean Antibody Titers (GMTs) for Anti-CS Antibodies by Infection Status PIII (M6.5)	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)	post dose 3 (month 6.5)
Other	Seropositivity Rates for Anti-CS Antibodies by Vaccine Group PRE	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	Prevaccination
Other	Seropositivity Rates for Anti-CS Antibodies by Vaccine Group PII (D60)	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)	1 month post dose 2
Other	Seropositivity Rates for Anti-CS Antibodies by Vaccine Group PIII (D90)	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)	1 month post dose 3
Other	Seropositivity Rates for Anti-CS Antibodies by Vaccine Group PIII (M6.5)	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)	4 months post dose 3
Other	Seropositivity Rates for Anti-CS Antibodies by Vaccine Group PIII (M12)	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)	10 months post dose 3
Other	Seropositivity Rates for Anti-CS Antibodies by Infection Status PRE	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	Prevaccination
Other	Seropositivity Rates for Anti-CS Antibodies by Infection Status PII (D60)	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)	post dose 2 (day 60)
Other	Seropositivity Rates for Anti-CS Antibodies by Infection Status PIII (D90)	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)	post dose 3 (day 90)
Other	Seropositivity Rates for Anti-CS Antibodies by Infection Status PIII (M6.5)	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)	post dose 3 (month 6.5)
Other	Efficacy: Vaccine Efficacy Against P. Falciparum Infection	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)	14 days after dose 3 and extending for 14 weeks
Other	Percentage of Participants With Positive and Negative Parasite Density	Percentage of participants with positive and negative parasite density at month 6.5	at month 6.5
Other	Geometric Mean Antibody Titers (GMTs) of Asexual P. Falciparum Parasitemia	Geometric Mean Antibody Titers (GMTs) of Asexual P. falciparum parasitemia at Month 6.5	Month 6.5
Primary	Safety: Proportion of Subjects With Grade 3 Solicited and Unsolicited General Reactions After Vaccination of RTS, S/AS02A and RTS, S/AS01B	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).	7 day follow-up (day of vaccination + 6 days)
Primary	Safety: Number of Administered Doses Eliciting Grade 3 Unsolicited Symptoms	Grade 3 unsolicited symptoms reported following any number of administered doses	6.5 months
Primary	Safety: Number of Doses Eliciting Solicited Local Symptoms Reported Over 7 Day Follow-up Period	Incidence overall solicited general and local reactions over 7 day follow-up period after dose 1, 2 and 3 (Total Cohort)	7 day follow-up period (day of vaccination + 6 days)
Secondary	Safety: Occurrence of SAEs	Percentage of subjects experiencing SAEs classified by MedRA System Organ Class and Preferred Term (Month 6.5-12)	months 6.5 thru 12
Secondary	Safety: Occurrence of SAEs	Percentage of subjects reporting SAEs classified by MedDRA System Organ Class and Preferred Term (Month 0-12)	months 0 thru 12
Secondary	Occurrence of Hematology Parameters Below Normal Range	Occurrence of hematology parameters below normal range (Total Cohort)	Days 0, 6, 66, and 90; Months 6 and 12
Secondary	Occurrence of Biochemistry Parameters Above Normal Ranges	Occurrence of parameters of biochemical monitoring above normal ranges (Total Cohort)	Days 0, 6, and 90