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Efficacy, Safety and Immunogenicity Study of GSK Biologicals' Candidate Malaria Vaccine (SB257049) Evaluating Schedules With or Without Fractional Doses, Early Dose 4 and Yearly Doses, in Children 5-17 Months of Age

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ClinicalTrials.gov Identifier: NCT03276962
Recruitment Status : Active, not recruiting
First Posted : September 8, 2017
Last Update Posted : May 29, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
The study intends to establish proof of concept for a fractional dose schedule under conditions of natural exposure in children 5-17 months old at first vaccination. The study also aims to establish the role of third dose spacing in a fractional dose schedule, describe the effect of an earlier full fourth dose at Month 14 and describe the effect of multiple fractional or full yearly doses.

Condition or disease Intervention/treatment Phase
Malaria Biological: RTS,S/AS01E (Full dose) Biological: RTS,S/AS01E (1/5th dose) Biological: Rabies vaccine Phase 2

Detailed Description:
The current study intends to establish proof of concept (POC) for a fractional dose schedule under conditions of natural exposure. The study will be conducted in children 5-17 months old at first vaccination living in areas of mid to high malaria transmission, in line with the age group recommended by the World Health Organization (WHO) for the implementation of the RTS,S/AS01E vaccine. Results from this study will be critical in informing future possibilities for the development of vaccine-based strategies which, in combination with other interventions, may contribute to the malaria elimination agenda.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Efficacy, Safety and Immunogenicity Study of GSK Biologicals' Candi-date Malaria Vaccine (SB257049) Evaluating Schedules With or With-out Fractional Doses, Early Dose 4 and Yearly Doses, in Children 5-17 Months of Age
Actual Study Start Date : September 28, 2017
Estimated Primary Completion Date : July 16, 2020
Estimated Study Completion Date : December 15, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: R012-20 Group
Subjects will receive full doses of RTS,S/AS01E at Month 0, Month 1, Month 2 and a full dose at Month 20.
Biological: RTS,S/AS01E (Full dose)
Subjects will receive intramuscular injection of RTS,S/AS01E (full dose: 0.5 ml).

Experimental: R012-14-mD Group
Subjects will receive a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and yearly full doses at Month 14, Month 26, Month 38.
Biological: RTS,S/AS01E (Full dose)
Subjects will receive intramuscular injection of RTS,S/AS01E (full dose: 0.5 ml).

Experimental: Fx012-14-mFxD Group
Subjects will receive a full dose of RTS,S/AS01E at Month 0, Month 1 and RTS,S/AS01E 1/5th dose at Month 2, Month 14, Month 26, Month 38.
Biological: RTS,S/AS01E (Full dose)
Subjects will receive intramuscular injection of RTS,S/AS01E (full dose: 0.5 ml).

Biological: RTS,S/AS01E (1/5th dose)
Subjects will receive intramuscular injection of RTS,S/AS01E (1/5th dose: 0.1 ml).

Experimental: Fx017-mFxD Group
Subjects will receive a full dose of RTS,S/AS01E at Month 0, Month 1 andRTS,S/AS01E 1/5th dose at Month 7, Month 20, Month 32.
Biological: RTS,S/AS01E (Full dose)
Subjects will receive intramuscular injection of RTS,S/AS01E (full dose: 0.5 ml).

Biological: RTS,S/AS01E (1/5th dose)
Subjects will receive intramuscular injection of RTS,S/AS01E (1/5th dose: 0.1 ml).

Experimental: Control Group
Subjects will receive rabies vaccine at Month 0, Month 1, Month 2.
Biological: Rabies vaccine
Subjects will receive intramuscular injection of rabies vaccine (0.1 ml).




Primary Outcome Measures :
  1. The occurrence of clinical malaria meeting the primary case definition. [ Time Frame: From Month 2.5 up to Month 14. ]
    The primary case definition will be P. falciparum asexual parasitemia > 5000 parasites/μl and presence of fever (axillary temperature ≥ 37.5°C) at the time of presentation and occurring in a child who is unwell and brought for treatment to a healthcare facility.


Secondary Outcome Measures :
  1. The occurrence of clinical malaria meeting the primary and secondary case definitions. [ Time Frame: From Day 0 up to Month 50. ]

    The primary case definition will be P. falciparum asexual parasitemia > 5000 parasites/μl and presence of fever (axillary temperature ≥ 37.5°C) at the time of presentation and occurring in a child who is unwell and brought for treatment to a healthcare facility.

    The secondary case definition will be P. falciparum asexual parasitemia > 0 and presence of fever (axillary temperature ≥ 37.5°C) at the time of presentation or history of fever within 24 hours of presentation and occurring in a child who is unwell and brought for treatment to a healthcare facility.


  2. The occurrence of incident P. falciparum infections. [ Time Frame: From Day 0 to Month 50. ]
    Vaccine efficacy against incident P. falciparum infections defined by positive blood slide.

  3. The prevalence of P. falciparum infections defined by positive blood slide at each cross-sectional survey. [ Time Frame: Monthly from Month 0-20 and every three months thereafter till study end (Month 50). ]
    Prevalence of P. falciparum infections of each RTS,S/AS01E schedule at cross-sectional visits.

  4. Number of seropositive subjects for anti-CS antibodies (in a sub-cohort of first 25 subjects enrolled in each group per site). [ Time Frame: Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), before and one month post-Dose 3, before and one month after Dose 4, before and one month after each yearly dose and at study end (Month 50). ]
    A seropositive subject is defined as a subject with antibody concentrations ≥ 0.5 EU/mL.

  5. Number of seropositive subjects for anti-HBs antibodies (in a sub-cohort of first 25 subjects enrolled in each group per site. [ Time Frame: Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), before and one month post-Dose 3, before and one month after Dose 4, before and one month after each yearly dose and at study end (Month 50). ]
    A seropositive subject is defined as a subject with antibody concentrations ≥ 10 mIU/mL.

  6. Antibody concentrations for anti-CS (in a sub-cohort of first 25 subjects enrolled in each group per site). [ Time Frame: Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), before and one month post-Dose 3, before and one month after Dose 4, before and one month after each yearly dose and at study end (Month 50). ]
    Concentrations are expressed as geometric mean concentrations.

  7. Antibody concentrations for anti-HBs. (in a sub-cohort of first 25 subjects enrolled in each group per site). [ Time Frame: Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), before and one month post-Dose 3, before and one month after Dose 4, before and one month after each yearly dose and at study end (Month 50). ]
    Concentrations are expressed as geometric mean concentrations.

  8. Number of subjects with any, fatal and related SAEs. [ Time Frame: From Day 0 to Month 50. ]
    SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  9. Number of subjects with any AE and SAE leading to withdrawal from further vaccination. [ Time Frame: From Day 0 to Month 50. ]

    An adverse event is any untoward medical occurrence in a clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.

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


  10. Number of subjects with severe malaria and cerebral malaria. [ Time Frame: From Day 0 to Month 50. ]

    Cerebral malaria is defined as Severe P. falciparum malaria with coma (Glasgow coma score < 11 in children two years of age or older [≥ 2 years] or Blantyre coma score < 3 in children less than two years of age [(< 2 years]); and If malaria with seizure: coma persisting for > 30 min after the seizure. Other treatable causes of coma should be excluded before diagnosing cerebral malaria (e.g. hypoglycaemia, bacterial meningitis).

    Severe malaria is defined as P. falciparum parasitemia > 0 detected by microscopy and/or rapid diagnostic test (RDT) and one or more of the following, occurring in the absence of an identified alternative cause: Impaired consciousness, Prostration, Multiple convulsions, Acidosis, Hypoglycemia, Severe malarial anemia,Renal impairment, Jaundice, Pulmonary edema, Significant bleeding: including recurrent or prolonged bleeding from the nose, gums or venipuncture sites, hematemesis or melaena, Shock, Hyperparasitemia.


  11. Number of subjects with potential Immune mediated diseases (pIMDs). [ Time Frame: From Day 0 to Month 50. ]
    Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.

  12. Number of subjects with meningitis. [ Time Frame: From Day 0 to Month 50. ]
    The number of subjects with meningitis per study group.

  13. Number of subjects with of seizures. [ Time Frame: During the 30-day (Days 0-29) follow up period after each dose of study vaccine. ]
    The number of subjects with seizures per study group.

  14. Number of subjects with generalized convulsive seizures. [ Time Frame: During the 7-day (Days 0-6) follow up period after each dose of study vaccine. ]
    The number of subjects with generalized convulsive seizures per study group.

  15. Number of subjects with any unsolicited AE(s). [ Time Frame: During the 30-day (Days 0-29) follow up period after each dose of study vaccine. ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.

  16. Number of subjects with abnormal laboratory values. (in a sub-cohort of first 25 subjects enrolled in each group per site). [ Time Frame: Before Dose 3, seven days post-Dose 3 and 30 days post-Dose 3. ]
    The assessed parameters will be summarised by toxicity grading scales and by group.

  17. Number of subjects with any solicited local and general symptoms. (in the reactogenity sub-cohort of first 25 subjects enrolled per site) [ Time Frame: During the 7-day (Days 0-6) follow-up period after each vaccination. ]
    Solicited local symptoms assessed will be pain, redness and swelling. Solicited general symptoms assessed will be drowsiness, fever, irritability/fussiness and loss of appetite.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   5 Months to 17 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects' parent(s)/LAR(s) who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. return for follow-up visits).
  • Signed or thumb-printed and witnessed informed consent obtained from the parent(s)/LAR(s) of the subject prior to performance of any study specific procedure. Where parent(s)/LAR(s) are illiterate, the consent form will be countersigned by an independent witness.
  • A male or female between, and including, five and 17 months of age at the time of the first vaccination.
  • Healthy subjects as established by medical history and clinical examination before entering into the study.
  • Previously received three documented doses of diphtheria, tetanus, pertussis, hepatitis B vaccine (DTPHepB), and at least three doses of oral polio vaccine.

Exclusion Criteria:

  • Child in care.
  • Use of a drug or vaccine that is not approved for that indication (by one of the following regulatory authorities: Food and Drug Administration [FDA; USA] or European Union member state or WHO [with respect to prequalification]) other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day -29 to Day 0), or planned use during the study period.
  • Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
  • Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone (0.5 mg/kg/day (for pediatric subjects) or equivalent. Inhaled and topical steroids are allowed.
  • Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting seven days before each dose and ending seven days after each dose of vaccine administration.
  • Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device).
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
  • Family history of congenital or hereditary immunodeficiency.
  • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
  • History of anaphylaxis post-vaccination.
  • History of any, or documented, serious adverse reaction to rabies vaccination.
  • Contraindication to rabies vaccination (Rabipur is contraindicated in subjects with an history of a severe hypersensitivity to any of the ingredients in the vaccine. Note that the vaccine contains polygeline and residues of chicken proteins, and may contain traces of neomycin, chlortetracycline and amphotericin B).
  • Major congenital defects.
  • Serious chronic illness.
  • Children with a past history of a neurological disorder or atypical febrile seizure (a febrile seizure is atypical if it meets one of the following criteria: not associated with fever; lasts > 5 minutes; focal (not generalized); followed by transient or persistent neurological abnormality; occurs in a child < 6 months of age).
  • Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 37.5°C/99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C/100.4°F for rectal route.

Subjects with a minor illness (such as mild diarrhea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator.

  • Administration of immunoglobulins and/or any blood products during the period starting three months before the first dose of study vaccine or planned administration during the study period.
  • Moderate or severe malnutrition at screening defined as weight for age or weight for height Z-score < -2.
  • Hemoglobin concentration < 8 g/dl at screening.
  • Same sex twins (to avoid misidentification).
  • Maternal death.
  • Prior receipt of an investigational malaria vaccine.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03276962


Locations
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Ghana
GSK Investigational Site
Kumasi, Ghana
Kenya
GSK Investigational Site
Kisumu, Kenya, 40100
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline

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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03276962     History of Changes
Other Study ID Numbers: 204889
2016-000290-20 ( EudraCT Number )
First Posted: September 8, 2017    Key Record Dates
Last Update Posted: May 29, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
falciparum, efficacy
RTS,S/AS01
malaria vaccine
safety
Malaria
immunogenicity
infants
Additional relevant MeSH terms:
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Malaria
Protozoan Infections
Parasitic Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs