AzTrials
AzTrials

MalariaPhase 2NCT00197028

Examine Safety and Immune Responses of GSK 257049 Vaccine When Administered to Infants Living in a Malaria-endemic Region

A Phase 2 study testing RTS,S/AS02D, TETRActHib™ and Engerix-B® in people with Malaria, run by GlaxoSmithKline at 1 site in Mozambique.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

GSK Biologicals is developing in partnership with the Program for Appropriate Technology in Health (PATH) Malaria Vaccine Initiative a candidate malaria vaccine for the routine immunization of infants and children living in malaria endemic areas. Read more about this study

Who is it for?
Ages 6 to 12 weeksHealthy volunteers can take part
Conditions the study is for
Malaria
What is being tested?
RTS,S/AS02D, TETRActHib™ and Engerix-B®
Could I receive a placebo?
No, everyone receives an active treatment
How many people
214 participants
Where
1 siteMozambique
Study dates
23 Aug 2005to 27 Dec 2007
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 to 12 weeks
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • A male or female infant of between 6 and 12 weeks of age at the time of first vaccination.
  • Written informed consent obtained from the parent(s) or guardian(s) of the subject
  • Free of obvious health problems as established by medical history and clinical examination before entering into the study.
  • Born to a mother who is hepatitis B surface antigen (HBsAg) negative and human immunodeficiency virus (HIV) negative.
  • Born after a normal gestation period (between 36 and 42 weeks).
  • Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study.

Who cannot join

  • Bacillus Calmette-Guérin tuberculosis vaccine (BCG) administration within one week of proposed administration of a study vaccine.
  • Use of any investigational or non-registered drug or vaccine other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
  • Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
  • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth
  • Any chronic drug therapy to be continued during the study period.
  • Previous vaccination with diphtheria, tetanus, pertussis, Haemophilus influenzae type b or hepatitis B vaccines.
Show all 17Show fewer
  • Major congenital abnormality.
  • Serious acute or chronic illness determined by clinical, physical examination and laboratory screening tests
  • Any medically diagnosed or suspected immunodeficient condition based on medical history and physical examination
  • A family history of congenital or hereditary immunodeficiency.
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
  • History of any neurological disorders or seizures.
  • Maternal death.
  • Hemoglobin < 80 g/L
  • Simultaneous participation in any other clinical trial.
  • Same sex twin
  • Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trialModerate malnutrition at screening

Trial locations and contacts

1 site in 1 country.

Mozambique1 site
  • GSK Investigational Site

    Maputo

Other trials in Mozambique

About this study

Official title: A Phase I/IIb Randomized, Double-blind, Controlled Study of the Safety, Immunogenicity and Proof-of-concept of RTS,S/AS02D, a Candidate Malaria Vaccine in Infants Living in a Malaria-endemic Region

GSK Biologicals is developing in partnership with the Program for Appropriate Technology in Health (PATH) Malaria Vaccine Initiative a candidate malaria vaccine 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).

This trial is being carried out following the demonstration of efficacy of a previous version of the malaria candidate vaccine in children in Mozambique: there, the vaccine demonstrated approximately 30% efficacy against clinical episodes of malaria and approximately 58% efficacy against severe malaria disease.

In order to integrate the malaria vaccine into the Expanded Program on Immunization (EPI) regimen, in malaria-endemic regions, for this trial, a 0.5 ml dose of GSK 257049 vaccine has been developed. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Read the detailed description

All infants participating in this phase I/IIb study will receive TETRActHib (a licensed diphtheria-tetanus-pertussis Haemophilus influenzae vaccine manufactured by Aventis Pasteur) by IM injection in their right thigh at 8, 12, and 16 weeks; They will be randomized to receive either the candidate malaria vaccine, GSK 257049 vaccine (0.5 ml dose) or Engerix-B (a licensed hepatitis B vaccine manufactured by GSK Biologicals) by IM injection in their left thigh at 10, 14, 18 weeks. Infants will be followed-up daily for 7 days after each vaccine dose for evaluation of safety and reactogenicity. There will be a 14-day follow-up period after each dose of TETRActHib and after Dose 1 and Dose 2 of GSK 257049 vaccine or Engerix-B, and a one month follow-up period after Dose 3 of GSK 257049 vaccine or Engerix-B for reporting unsolicited symptoms. Serious adverse events will be recorded throughout the 14 month study period. A small amount of blood (2 ml = 1/2 teaspoon) will be obtained at four different time points to measure the immune response elicited by the vaccines administered during this study period. Preliminary indication of vaccine efficacy in this age group will be established by actively monitoring for infection with Plasmodium falciparum.

Conditions
Malaria
Being tested
RTS,S/AS02D, TETRActHib™, Engerix-B®
Medical subject headings
Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RTS,S/AS02DBiological

    3-dose intramuscular injection in the thigh

  • TETRActHib™Biological

    3-dose intramuscular injection in the thigh.

  • Engerix-B®Biological

    3-dose intramuscular injection in the thigh.

Study groups in NCT00197028
Study groupRoleWhat they receive
RTS,S/AS02D GroupExperimentalSubjects aged between 6 and 12 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of RTS,S/AS02D at days 14, 44 and 74 and a 3-dose vaccination course of TETRActHib™ vaccine at days 0, 30 and 60. The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Receives: Biological: RTS,S/AS02D; Biological: TETRActHib™
Engerix-B GroupActive comparatorSubjects aged between 6 and 12 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine at days 14, 44 and 74 and a 3-dose of TETRActHib™ vaccine at days 0, 30 and 60. The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Receives: Biological: TETRActHib™; Biological: Engerix-B®

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Subjects With Serious Adverse Events (SAEs).

    SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.

    Measured: From Month 0 to Month 6

Secondary outcomes (17)
  1. Number of Subjects With Serious Adverse Events (SAEs).

    SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.

    Measured: Throughout the entire study period (from Month 0 to Month 14)

  2. Concentrations of Antibodies Against Hepatitis B (Anti-HB)

    Concentrations were expressed as geometric mean concentrations (GMCs) in milli-international unit per milliliter (mIU/mL). The seroprotection cut-off of the assay was 10 mIU/mL.

    Measured: Prior to vaccination at Month 0 (PRE) and 1 month post Dose 3 of Engerix-B® or RTS,S/AS02D vaccine (Day 104).

  3. Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies.

    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 seropositivity cut-off of the assay was 0.5 EL.U/mL.

    Measured: Prior to vaccination at Month 0 (PRE), 1 month post Dose 3 of Engerix-B® or RTS,S/AS02D vaccine (Day 104) and 3½ months post Dose 3 of Engerix-B® or RTS,S/AS02D vaccine (Day 180).

  4. Concentrations of Antibodies Against Anti-diphtheria (Anti-D)

    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 seroprotection cut-off of the assay was 0.1 IU/mL.

    Measured: At Day 90 (1 month post Dose 3 of TETRActHib™ vaccine)

  5. Concentrations of Antibodies Against Tetanus (Anti-T)

    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 seroprotection cut-off of the assay was 0.1 IU/mL.

    Measured: At Day 90 (1 month post Dose 3 of TETRActHib™ vaccine)

  6. Concentrations of Anti-Bordetella Pertussis Toxin Antibodies (Anti-BPT).

    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 seropositivity cut-off of the assay was 15 EL.U/mL.

    Measured: At Day 90 (1 month post Dose 3 of TETRActHib™ vaccine)

  7. Concentrations of Anti-polyribosyl Ribitol Phosphate Antibodies (Anti-PRP).

    Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per milliliter (µg/mL). The seroprotection cut-off of the assay was 0.15 µg/mL.

    Measured: At Day 90 (1 month post Dose 3 of TETRActHib™ vaccine)

  8. Time to First Malaria Infection

    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.

    Measured: Over the period starting 14 days after Dose 3 of RTS,S/AS02D or Engerix-B® vaccine and extending for 12 weeks thereafter (from Month 2.5 to Month 6)

  9. Number of Subjects Prevalent for Plasmodium Falciparum (P. Falciparum)

    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.

    Measured: At Month 6 (3½ months post Dose 3 of RTS,S/AS02D or Engerix-B® vaccine)

  10. Plasmodium Falciparum (P. Falciparum) Parasite Density in Subjects Prevalent for Parasitemia

    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 3 ½ months after administration of Dose 3 of RTS,S/AS02D or Engerix-B® vaccine (Month 6). Parasite density is expressed as mean, minimum and maximum density in parasite per µL.

    Measured: At Month 6 (3½ months post Dose 3 of RTS,S/AS02D or Engerix-B® vaccine)

  11. Number of Subjects With Solicited Local Symptoms.

    Assessed solicited local symptoms were pain and swelling at injection site.

    Measured: During the 7 day (Days 0-6) follow-up period after any vaccination with TETRActHib™ vaccine.

  12. Number of Subjects With Solicited Local Symptoms.

    Assessed solicited local symptoms were pain and swelling at injection site.

    Measured: During the 7 day (Days 0-6) follow-up period after any vaccination with Engerix-B® or RTS,S/AS02D vaccine.

  13. Number of Subjects With Solicited General Symptoms.

    Assessed solicited general symptoms were drowsiness, fever, irritability and loss of appetite. Fever was defined as axillary temperature equal or above (≥) to 37.5 degrees Celsius (C).

    Measured: During the 7 day (Days 0-6) follow-up period after any vaccination with TETRActHib™ vaccine

  14. Number of Subjects With Solicited General Symptoms.

    Assessed solicited general symptoms were drowsiness, fever, irritability and loss of appetite. Fever was defined as axillary temperature equal or above (≥) to 37.5 degrees Celsius (C).

    Measured: During the 7 day (Days 0-6) follow-up period after any vaccination with Engerix-B® or RTS,S/AS02D vaccine

  15. Number of Subjects With Unsolicited Adverse Events (AEs).

    An unsolicited AE is any AE (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.

    Measured: During the 14 day (Days 0-13) follow-up period after any vaccination with of TETRActHib™ vaccine

  16. Number of Subjects With Unsolicited Adverse Events (AEs).

    An unsolicited AE is any AE (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.

    Measured: During the 14 day (Days 0-13) follow-up period after vaccination with any among Doses 1 and 2 of Engerix-B® or RTS,S/AS02D vaccine.

  17. Number of Subjects With Unsolicited Adverse Events (AEs).

    An unsolicited AE is any AE (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.

    Measured: During the 30 day (Days 0-29) follow-up period after vaccination with Dose 3 of Engerix-B® or RTS,S/AS02D vaccine.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2005 (estimated)
  2. Study start23 Aug 2005
  3. Primary completion27 Dec 2007
  4. Study completion27 Dec 2007

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Care provider, Investigator, Outcomes assessor
Enrolment
214 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00197028
Sponsor's protocol ID
103967
Status last verified
Apr 2017
First submitted
13 Sep 2005
Last updated
20 Aug 2018
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

  • Aide P, Aponte JJ, Renom M, Nhampossa T, Sacarlal J, Mandomando I, Bassat Q, Manaca MN, Leach A, Lievens M, Vekemans J, Dubois MC, Loucq C, Ballou WR, Cohen J, Alonso PL. Safety, immunogenicity and duration of protection of the RTS,S/AS02(D) malaria vaccine: one year follow-up of a randomized controlled phase I/IIb trial. PLoS One. 2010 Nov 4;5(11):e13838. doi: 10.1371/journal.pone.0013838.

    PubMed 21079803
  • Aponte JJ, Aide P, Renom M, Mandomando I, Bassat Q, Sacarlal J, Manaca MN, Lafuente S, Barbosa A, Leach A, Lievens M, Vekemans J, Sigauque B, Dubois MC, Demoitie MA, Sillman M, Savarese B, McNeil JG, Macete E, Ballou WR, Cohen J, Alonso PL. Safety of the RTS,S/AS02D candidate malaria vaccine in infants living in a highly endemic area of Mozambique: a double blind randomised controlled phase I/IIb trial. Lancet. 2007 Nov 3;370(9598):1543-51. doi: 10.1016/S0140-6736(07)61542-6. Epub 2007 Oct 18.

    PubMed 17949807

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RTS,S/AS02D, TETRActHib™ and Engerix-B® in people with Malaria, run by GlaxoSmithKline at 1 site in Mozambique.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Mozambique. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jan 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With Serious Adverse Events (SAEs). (time frame: From Month 0 to Month 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00197028, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2018; AzTrials last refreshed its copy on 8 Nov 2026.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in