Study of Safety, Immunogenicity and Efficacy of a Candidate Malaria Vaccine in Tanzanian Infants

Phase 2

Completed

• Conditions: Malaria; Malaria Vaccines
• Interventions: Biological: Engerix-B®; Biological: RTS,S/AS02D; Biological: TETRActHib™

• Registration Number: NCT00289185
• Lead Sponsor: GlaxoSmithKline

Brief Summary

GSK Biologicals in partnership with the Malaria Vaccine Initiative at PATH is developing a candidate malaria vaccine GSK 257049 for the routine immunization of infants and children living in malaria endemic areas. The vaccine would offer protection against malaria disease due to the parasite Plasmodium falciparum. The vaccine would also provide protection against infection with hepatitis B virus (HBV).

In order to integrate the malaria vaccine into the EPI regimen in malaria-endemic regions, a new variant RTS,S/AS02D (0.5 mL dose) has been developed.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed Description

This is a phase 2b trial designed to evaluate the safety and immunogenicity of RTS,S/AS02D when co-administered with a multivalent DTPw/Hib (Aventis Pasteur's TETRActHib vaccine). Infants randomized to the control group will receive a licensed hepatitis B vaccine, Engerix-B in place of RTS,S/AS02D.

Data pertaining to RTS,S/AS02D or Engerix-B will be collected in a double blinded manner; data relating to TETRActHib will be collected in an open fashion.

Oral polio vaccine (OPV) will be administered at birth, 8, 12, 16 weeks in co-administration with other vaccines and will not be administered as part of this protocol. Antibody titers to OPV will not be assessed as part of this protocol.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2006-02-08
• Study First Submitted QC: 2006-02-08
• Study First Posted: 2006-02-09
• Study Start: 2006-09-27
• Primary Completion: 2008-02-11
• Study Completion: 2009-01-15
• Disposition First Submitted: 2009-09-03
• Disposition First Submitted QC: 2009-09-03
• Disposition First Posted: 2009-09-04
• Results First Submitted: 2012-11-08
• Results First Submitted QC: 2013-04-25
• Results First Posted: 2013-07-08
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-08
• Last Update Posted: 2020-10-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 340

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Engerix-B Group	Engerix-B®	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh..
RTS,S/AS02D Group	RTS,S/AS02D	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
RTS,S/AS02D Group	TETRActHib™	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Engerix-B Group	TETRActHib™	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh..

Primary Outcome Measures

Name	Time	Method
Concentrations of Antibodies Against Hepatitis B (Anti-HB)	Prior to vaccination at Week 0 (PRE), at Month 2 and at Month 3.	Concentrations were expressed as geometric mean concentrations (GMCs) in milli-international unit per milliliter (mIU/mL). The cut-off of the assay was the seroprotection cut-off of 10 mIU/mL. Month 3 results are the specific results for this primary outcome measure.
Concentrations of Anti-Bordetella Pertussis Toxin Antibodies (Anti-BPT).	Prior to vaccination at Week 0 (PRE), and at Month 3.	Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EL.U/mL). The cut-off of the assay was the seropositivity cut-off of 15 EL.U/mL. Month 3 results are the specific results for this primary outcome measure.
Number of Subjects With Anti-diphtheria Antibody (Anti-D) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value	Prior to vaccination at Week 0 (PRE), and at Month 3.	Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). The seroprotection cut-off value was 0.1 international unit per milliliter (IU/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), and at Month 3. Month 3 results are the specific results for this primary outcome measure.
Number of Subjects With Anti-tetanus Antibody (Anti-T) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value	Prior to vaccination at Week 0 (PRE), and at Month 3.	Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). The seroprotection cut-off value was 0.1 international unit per milliliter (IU/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), and at Month 3. Month 3 results are the specific results for this primary outcome measure.
Number of Subjects With Hepatitis B Antibody (Anti-HB) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value	Prior to vaccination at Week 0 (PRE), at Month 2 and at Month 3.	The seroprotection cut-off value was 10 milli-international units per milliliter (mIU/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), at Month 2 and at Month 3. Month 3 results are the specific results for this primary outcome measure.
Concentrations of Anti-polyribosyl Ribitol Phosphate Antibodies (Anti-PRP).	Prior to vaccination at Week 0 (PRE), and at Month 3.	Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per milliliter (µg/mL). The cut-off of the assay is the seroprotection cut-off value of 0.15 µg/mL. Month 3 results are the specific results for this primary outcome measure.
Number of Subjects With Serious Adverse Events (SAEs)	From Month 9 to Month 20.	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Concentrations of Antibodies Against Tetanus (Anti-T)	Prior to vaccination at Week 0 (PRE), and at Month 3.	Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in international unit per milliliter (IU/mL). The cut-off of the assay was the seroprotection cut-off of 0.1 IU/mL. Month 3 results are the specific results for this primary outcome measure.
Concentrations of Antibodies Against Diphtheria (Anti-D)	Prior to vaccination at Week 0 (PRE), and at Month 3.	Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in international unit per milliliter (IU/mL). The cut-off of the assay was the seroprotection cut-off of 0.1 IU/mL. Month 3 results are the specific results for this primary outcome measure.
Number of Subjects With Anti-polyribosyl Ribitol Phosphate Antibody (Anti-PRP) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value	Prior to vaccination at Week 0 (PRE), and at Month 3.	Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). The seroprotection cut-off value was 0.15 microgram per milliliter (µg/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), and at Month 3. Month 3 results are the specific results for this primary outcome measure.
Number of Subjects With Anti-Bordetella Pertussis Toxin Antibody (Anti-BPT) Concentrations Equal to or Above (>=) the Seropositivity Cut-off Value	Prior to vaccination at Week 0 (PRE), and at Month 3.	Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). The seropositivity cut-off value was 15 ELISA units per milliliter (EL.U/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), and at Month 3. Month 3 results are the specific results for this primary outcome measure.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Solicited Local Symptoms.	Within 7 days (Days 0-6) after vaccination with the TETRActHib vaccine.	Assessed solicited local symptoms were pain and swelling following vaccination with the TETRActHib vaccine..
Concentrations of Anti-Circumsporozoite Protein (Anti-CS) Antibodies	Prior to vaccination at Week 0 (PRE), at Month 2, at Month 3 and at Month 9.	Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations are expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EL.U/mL). The cut-off of the assay was the seropositivity cut-off value of 0.5 EL.U/mL.
Number of Subjects With Solicited General Symptoms.	Within 7 days (Days 0-6) after vaccination	Assessed solicited general symptoms were drowsiness, fever, irritability, and loss of appetite. Fever was defined as axillary temperature above or equal to (\>=) 37.5 degrees Celsius (°C).
Number of Subjects With Serious Adverse Events (SAEs)	Throughout the entire study, from Week 0 to Month 20.	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time to First Malaria Infection	Over the period starting 14 days after Dose 3 of RTS,S or HBV vaccine and extending for 6 months thereafter (from Month 2.5 up to Month 9).	Malaria infection by Plasmodium falciparum (P. falciparum) was detected by active detection of infection (ADI) and passive case detection (PCD), and was defined as the presence of P. falciparum asexual parasitemia above 0 per microliter (µL) on Giemsa stained thick blood films. The time to first malaria infection is expressed in terms of rate of first malaria infection, that is, the number of malaria infection events reported (n) over the period elapsed until the event occurred (i.e. events per Persons Year at Risk \[PYAR\]) for each group.
Number of Subjects Prevalent for Parasitemia	At Month 9	Subjects prevalent for P. falciparum parasitemia were defined as subjects with the presence of P. falciparum asexual parasitemia above 0 per microliter (µL) on Giemsa stained thick blood films.
Number of Subjects With Unsolicited Adverse Events (AEs).	Within 30 days (Days 0-29) after vaccination	An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Plasmodium Falciparum (P. Falciparum) Parasite Density in Subjects Prevalent for Parasitemia	At Month 9	The parasite density in subjects prevalent for P. falciparum parasitemia (Subjects with the presence of P. falciparum asexual parasitemia above 0 per microliter (µL) on Giemsa stained thick blood films), was detected at a cross sectional time point 7 months after administration of Dose 3 of RTS,S or HBV vaccine (Month 9). Parasite density is expressed as mean, minimum and maximum density in parasite per µL. This outcome for solely assessed in the Engerix-B Group, as no subject in the RTS,S/AS02D was assessed as prevalent for parasitemia.

Trial Locations

Locations (1)

GSK Investigational Site; 🇹🇿 Dar-es-Salaam, Tanzania