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

NCT00197054 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: A-12227IND 11220
• Study Type: interventional
• Target: 255
• Locations: 1 country
• Sites: 1

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.

Conditions

Plasmodium Falciparum

Outcome Measures

Primary Outcomes (3)

• 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)

• Safety: Number of Administered Doses Eliciting Grade 3 Unsolicited Symptoms

  Grade 3 unsolicited symptoms reported following any number of administered doses

  6.5 months

• 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 Outcomes (4)

• Safety: Occurrence of SAEs

  months 6.5 thru 12

• Safety: Occurrence of SAEs

  months 0 thru 12

• Occurrence of Hematology Parameters Below Normal Range

  Days 0, 6, 66, and 90; Months 6 and 12

• Occurrence of Biochemistry Parameters Above Normal Ranges

  Days 0, 6, and 90

Other Outcomes (36)

• Seropositivity Rates for Anti-HBs Antibodies by Infection Status PRE

  Prevaccination

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

  Day 90

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

  Month 12

Study Arms (3)

VACC 1 (RTS, S/AS01B)

EXPERIMENTAL

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.

Biological: RTS, S/AS01B

VACC 2 (RTS, S/AS02A)

EXPERIMENTAL

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.

Biological: RTS, S/AS02A

Rabipur (Rabies) Vaccine

ACTIVE COMPARATOR

Rabipur (Rabies) Vaccine: 1.0mL dose administered intramuscular deltoid of non-dominant arm at 0, 1 and 2 months.

Biological: Rabipur (Rabies) Vaccine

Interventions

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.

VACC 1 (RTS, S/AS01B)

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.

VACC 2 (RTS, S/AS02A)

Rabipur (Rabies) Vaccine BIOLOGICAL

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

Rabipur (Rabies) Vaccine

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• GlaxoSmithKline: collaborator
• Walter Reed Army Institute of Research (WRAIR): collaborator

Study Sites (1)

U.S. Army Research Unit-Kenya

Kisumu, Kenya

Location

Related Publications (1)

• 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.

  PMID: 19649245 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

RTS,S-AS01B vaccine; RTS,S-AS02A vaccine; Vaccines

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Results Point of Contact

• Title: LTC Mark Polhemus MD, MC
• Organization: Kombewa Clinic, US Army Medical Research Unit, Kisumo Kenya

GSKClinicalSupportHD@gsk.com

877-379-3788

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 20, 2005
• Study Start: July 1, 2005
• Primary Completion: September 1, 2006
• Study Completion: September 1, 2006
• Last Updated: February 12, 2021
• Results First Posted: December 11, 2020

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

KE (1)