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MalariaPhase 3NCT01148459

Safety and Immunogenicity of GSK Biologicals' Investigational Malaria Vaccine in HIV Infected Infants and Children

A Phase 3 study testing GSK Biological's Investigational Malaria Vaccine 257049, Human Diploid Cell Vaccine (HDCV) or Purified Vero Cell Rabies Vaccine (PVRV, Verorab) (Aventis Pasteur); and Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine (Rabipur or equivalent) (Novartis). in people with Malaria, run by GlaxoSmithKline at 2 sites in Kenya.

Completed

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

Official record
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Trial summary

The purpose of this study is to assess the safety and immunogenicity of the candidate malaria vaccine in HIV-infected infants and children Read more about this study

Who is it for?
Ages 6 weeks to 17 months
Conditions the study is for
Malaria
What is being tested?
GSK Biological's Investigational Malaria Vaccine 257049, Human Diploid Cell Vaccine (HDCV) or Purified Vero Cell Rabies Vaccine (PVRV, Verorab) (Aventis Pasteur); and Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine (Rabipur or equivalent) (Novartis).
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
2 sitesKenya
Study dates
30 Jul 2010to 24 May 2013
Phase
Phase 3
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 weeks to 17 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • All subjects must satisfy ALL the following criteria at study entry:
  • A male or female infant or child between and including 6 weeks to 17 months of age, at the time of first vaccination.
  • Signed or thumb-printed informed consent obtained from the parent(s)/LAR(s) of the infant or child. Where parents/LARs are illiterate, the consent form will be countersigned by a witness.
  • Subjects who the investigator believes that their parents/LARs can and will comply with the requirements of the protocol should be enrolled in the study.
  • Subjects who are known to be HIV-infected (documented positive DNA PCR), whether taking HIV antiretroviral treatment (ART) or not.
  • Subjects who are born following a normal gestation period.

Who cannot join

  • The following criteria should be checked at the time of study entry. If ANY exclusion criterion applies, the subject must not be included in the study:
  • Acute disease at the time of enrolment. However, the presence of an illness listed as Grade I or Grade II (WHO pediatric AIDS clinical staging) will not of itself constitute an exclusion criterion. Enrolment should be deferred if axillary temperature is >=37.5°C.
  • Grade III or Grade IV abnormality on screening laboratory blood sample.
  • Grade III or IV AIDS at the time of enrolment (WHO pediatric AIDS clinical staging).
  • Major congenital defects.
  • Planned administration/administration of a vaccine not foreseen by the study protocol prior to or within 7 days of study vaccine.
Show all 13Show fewer
  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine 30 days preceding Dose°1 of study vaccine, or planned use during the study period.
  • Previous participation in any other malaria vaccine trial.
  • Simultaneous participation in another clinical trial including administration of experimental treatment.
  • Same sex twins.
  • History of allergic reactions (significant IgE-mediated events) or anaphylaxis to previous immunizations.
  • History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine.
  • Child in care.

Trial locations and contacts

2 sites in 1 country.

Kenya2 sites
  • GSK Investigational Site

    Kisian

  • GSK Investigational Site

    Kisumu

Other trials in Kenya

About this study

Official title: Safety and Immunogenicity Study of GSK Biologicals' Plasmodium Falciparum Malaria Vaccine 257049 Administered to HIV Infected Infants and Children

The purpose of this study is to assess the safety and immunogenicity of the candidate malaria vaccine in HIV-infected infants and children

Read the detailed description

This protocol posting has been updated due to protocol Amendment 2.

Conditions
Malaria
Being tested
GSK Biological's Investigational Malaria Vaccine 257049, Human Diploid Cell Vaccine (HDCV) or Purified Vero Cell Rabies Vaccine (PVRV, Verorab) (Aventis Pasteur);, Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine (Rabipur or equivalent) (Novartis).
Keywords
Plasmodium falciparum, schedule, HIV, malaria vaccine, EPI, Africa
Medical subject headings
Malaria, Malaria, Falciparum

What participants receive

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

  • GSK Biological's Investigational Malaria Vaccine 257049Biological

    All infants enrolled to group A will receive 3 doses of the experimental vaccine. The vaccine will be administered intramuscularly.

  • Human Diploid Cell Vaccine (HDCV) or Purified Vero Cell Rabies Vaccine (PVRV, Verorab) (Aventis Pasteur);Biological

    To ensure consistent vaccine availability, three cell culture rabies vaccines from two manufacturers may be sourced for this trial (Aventis-Pasteur and Novartis). It will be ensured that an individual child will receive all 3 doses of cell culture rabies vaccine from the same product.

    The vaccine will be administered intramuscularly

  • Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine (Rabipur or equivalent) (Novartis).Biological

    To ensure consistent vaccine availability, three cell culture rabies vaccines from two manufacturers may be sourced for this trial (Aventis-Pasteur and Novartis). It will be ensured that an individual child will receive all 3 doses of cell culture rabies vaccine from the same product.

    The vaccine will be administered intramuscularly.

Study groups in NCT01148459
Study groupRoleWhat they receive
Group AExperimentalInfants enrolled to this group will receive 3 doses of the experimental vaccine.
Receives: Biological: GSK Biological's Investigational Malaria Vaccine 257049
Group BActive comparatorInfants enrolled to this group will receive 3 doses of the rabies comparator vaccine.
Receives: Biological: Human Diploid Cell Vaccine (HDCV) or Purified Vero Cell Rabies Vaccine (PVRV, Verorab) (Aventis Pasteur);; Biological: Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine (Rabipur or equivalent) (Novartis).

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 assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

    Measured: During the entire study period (from 30 days before Dose 1 up to Month 14)

Secondary outcomes (18)
  1. Number of Subjects With Any and Grade 3 Solicited Local Symptoms

    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond (>) 20 millimeters (mm) of injection site.

    Measured: During the 7-day post-vaccination period following each dose and across doses: Day 1 through Day 7, Month 1 through Month 1 + 7 days (Day 37), Month 2 through Month 2 + 7 days (Day 67)

  2. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

    Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 irritability/fussiness = crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as causally related to the study vaccination.

    Measured: During the 7-day post-vaccination period following each dose and across doses: Day 1 through Day 7, Month 1 through Month 1 + 7 days (Day 37), Month 2 through Month 2 + 7 days (Day 67)

  3. Number of Subjects With Any Unsolicited Adverse Events (AEs)

    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

    Measured: During the 30-day post-vaccination period (up to Day 90)

  4. Number of Subjects With Non-malaria Related SAEs

    SAEs (excluding malaria, cerebral malaria and P. falciparum parasitemia) assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

    Measured: During the entire study period (from 30 days before vaccine Dose 1 up to Month 14)

  5. Anti-circumsporozoite Protein of P. Falciparum (Anti-CS) Antibody Concentrations

    Anti-CS antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). The reference seropositivity cut-off value was equal to or above (≥) 0.5 EL.U/mL.

    Measured: Prior to vaccination (PRE) and one month post Dose 3 (Month 3)

  6. Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Titers

    Anti-HBs antibody titers are presented as geometric mean titers (GMTs), expressed in milliinternational units per milliliter (mIU/mL).

    Measured: Prior to vaccination (PRE) and one month post Dose 3 (Month 3)

  7. Anti-CS Antibody Concentrations

    Anti-CS antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). The reference seropositivity cut-off value was equal to or above (≥) 0.5 EL.U/mL.

    Measured: 12 months post Dose 3 (Month 14)

  8. Anti-HBs Antibody Titers

    Anti-HBs antibody titers are presented as geometric mean titers (GMTs), expressed in mIU/mL.

    Measured: 12 months post Dose 3 (Month 14)

  9. Number of Episodes With Clinical Malaria Disease According to Primary Case Definition

    Primary case definition for clinical malaria: P. falciparum asexual parasitemia > 2500 parasites/μL and presence of fever (axillary temperature ≥ 37.5°C) at the time of presentation and occurring in a child who was unwell and brought for treatment to a healthcare facility.

    Measured: From Day 0 to Month 14

  10. Number of Episodes With Severe Malaria According to Primary Case Definition

    The number of episodes of severe malaria of primary case definition within and outside risk period. Primary case definition for severe malaria: P. falciparum > 2500 parasites per μL and with one or more marker of disease severity and without a diagnosis of co-morbidity.

    Measured: From Day 0 to Month 14

  11. Number of Subjects Affected by Prevalent Parasitemia and Prevalent Moderate Anemia

    The number of subjects affected by prevalent asexual P. falciparum parasitemia and prevalent moderate anemia. Moderate anemia = hemoglobin < 8 g/dL.

    Measured: 12 months post Dose 3 (Month 14)

  12. Asexual P. Falciparum Parasitemia Density

    The number of subjects with a positive blood slide for asexual P. falciparum.

    Measured: 12 months post Dose 3 (Month 14)

  13. Prevalent Hemoglobin Level

    The prevalent hemoglobin level in subjects with a positive blood slide is reported as grams per deciliter (g/dl).

    Measured: 12 months post Dose 3 (Month 14)

  14. HIV Viral Load

    The HIV viral load is reported. Detectable HIV viral load: 400 or more copies/mL.

    Measured: At baseline (PRE) and at one month (Month 3), 6 months (Month 8) and 12 months (Month 14) post Dose 3

  15. Percentage of CD4+ Cells

    The percentage of CD4+ cells is reported.

    Measured: At baseline (PRE) and at one month (Month 3), 6 months (Month 8) and 12 months (Month 14) post Dose 3

  16. CD4+ Absolute Cell Counts

    The CD4+ absolute cell counts are reported.

    Measured: At baseline (PRE) and at 1 month (Month 3), 6 months (Month 8) and 12 months (Month 14) post Dose 3

  17. World Health Organization (WHO) HIV Clinical Classification Progression

    Clinical staging was done at each time point according to the WHO HIV/AIDS clinical staging system. Clinical stages included:

    • "Stage 1" (asymptomatic or have persistent generalized lymphadenopathy),
    • "Stage 2" (mildly symptomatic stage - presenting with unexplained weight loss of less than 10 percent of total body weight, recurrent respiratory infections or dermatological conditions),
    • "Stage 3" (moderately symptomatic stage - presenting with weight loss of greater than 10 percent of total body weight, prolonged unexplained diarrhea or pulmonary tuberculosis, severe systemic bacterial infections or mucocutaneous conditions),
    • "Stage 4" (severely symptomatic stage which includes all of the AIDS-defining illnesses) Additional categories included "deceased" and "missing".

    Measured: At baseline (PRE), at study months 1 (Month 1) and 2 (Month 2) and at 1 month (Month 3), 6 months (Month 8) and 12 months (Month 14) post Dose 3

  18. Growth Parameters: Weight, Age/Length and Middle Upper Arm Circumference for Age Z-score

    The following growth parameters: weight, age/length and middle upper arm circumference for age z-score are reported.

    Measured: At baseline (PRE), at Month 3 and at study end (Month 14)

Timeline

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

  1. First posted22 Jun 2010 (estimated)
  2. Study start30 Jul 2010
  3. Primary completion24 May 2013
  4. Study completion24 May 2013

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 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
200 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01148459
Sponsor's protocol ID
112745
Status last verified
May 2017
First submitted
17 Jun 2010
Last updated
16 Jan 2019
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

  • Otieno L, Oneko M, Otieno W, Abuodha J, Owino E, Odero C, Mendoza YG, Andagalu B, Awino N, Ivinson K, Heerwegh D, Otsyula N, Oziemkowska M, Usuf EA, Otieno A, Otieno K, Leboulleux D, Leach A, Oyieko J, Slutsker L, Lievens M, Cowden J, Lapierre D, Kariuki S, Ogutu B, Vekemans J, Hamel MJ. Safety and immunogenicity of RTS,S/AS01 malaria vaccine in infants and children with WHO stage 1 or 2 HIV disease: a randomised, double-blind, controlled trial. Lancet Infect Dis. 2016 Oct;16(10):1134-1144. doi: 10.1016/S1473-3099(16)30161-X. Epub 2016 Jul 7.

    PubMed 27394191

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing GSK Biological's Investigational Malaria Vaccine 257049, Human Diploid Cell Vaccine (HDCV) or Purified Vero Cell Rabies Vaccine (PVRV, Verorab) (Aventis Pasteur); and Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine (Rabipur or equivalent) (Novartis). in people with Malaria, run by GlaxoSmithKline at 2 sites in Kenya.

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 13 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 16 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Kenya. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 16 Jan 2019). 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: During the entire study period (from 30 days before Dose 1 up to Month 14)). 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 NCT01148459, which also lists 1 linked publication.

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 16 Jan 2019.

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