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

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2016-000290-20-Outside-EU/EEA
• Date of registration: 22/09/2017
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Biologicals
• Public title: 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
• Scientific title: Phase IIb randomized, open-label, controlled, multi-center study of the efficacy, safety and immunogenicity of GSK Biologicals’ candidate malaria vaccine RTS,S/AS01E evaluating schedules with or without fractional doses, early Dose 4 and yearly doses, in children 5-17 months of age living in sub-Saharan Africa - MALARIA-094
• Target sample size: 1500
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000290-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 5
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Ghana, Kenya

Contacts

• Name: Clinical Disclosure Advisor
• Affiliation: GlaxoSmithKline Biologicals

• Name: Clinical Disclosure Advisor
• Affiliation: GlaxoSmithKline Biologicals

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects’ parent(s)/LAR(s) who, in the opinion of the investigator, can and will comply with the require-ments 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 independ-ent 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 diph-theria, tetanus, pertussis, hepatitis B vaccine (DTPHepB), and at least three doses of oral polio vaccine.
Are the trial subjects under 18? yes
Number of subjects for this age range: 1500
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 prequalifi-cation]) 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 contra-indicated in subjects with an history of a severe hyper-sensitivity 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 = 37.5C/99.5F for oral, axillary or tympanic route, or = 38.0C/100.4F for rectal route.
? Subjects with a minor illness (such as mild diar-rhea, 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Parasitic Diseases [C03]

Healthy volunteers (primary immunization against malaria disease caused by Plasmodium falciparum)
MedDRA version: 20.0 Level: PT Classification code 10025487 Term: Malaria System Organ Class: 10021881 - Infections and infestations

Intervention(s)

Product Name: Candidate Plasmodium falciparum malaria vaccine
Product Code: RTS,S+AS01E
Pharmaceutical Form: Powder and suspension for suspension for injection
INN or Proposed INN: -
Current Sponsor code: RTS,S
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: RABIPUR
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: -
Other descriptive name: RABIES VIRUS (INACTIVATED) STRAIN FLURY LEP
Concentration unit: IU international unit(s)
Concentration type: not less then
Concentration number: 2.5-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: From Month 2.5 up to Month 14

Secondary Objective: To assess the incremental vaccine efficacy against clinical malaria of a schedule with a:
-fractional third dose at Month 2 versus 3 full doses.
-fractional third dose at Month 7 versus a fractional third dose at month 2 or 3 full doses.
-fractional third dose at month 2 and yearly fractional doses versus full doses and yearly full doses.
-fractional third dose at Month 7 versus a standard schedule with 4 full doses at 0,1,2,20 months.
To assess:
-the VE and impact of each schedule.
-the prevalence of P. falciparum infections of each schedule at cross-sectional visits.
-the VE against incident P. falciparum infections defined by positive blood slide.
To describe the antibody response to the anti-circumsporozoite protein of P. falciparum (anti-CS) and hepatitis B surface antigen (anti-HBs) for each schedule.
To assess the safety in terms of SAEs, unsolicited adverse events (AEs) and AEs of specific interest, local and general AEs, haemtology and biochemistry parameters.

Primary end point(s): The occurrence of clinical malaria meeting the primary case definition

Main Objective: To demonstrate the superiority of a 3-dose schedule of GSK Biologicals’ malaria vaccine RTS,S/AS01E with a fractional third dose at Month 2 compared to a standard schedule of RTS,S/AS01E with three full doses in terms of vaccine efficacy against clinical malaria (primary case definition) over 12 months post-Dose 3.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Day 0-Month 50
Day 0-Month 50
Monthly from Month 0-20; every 3months thereafter till Month 50
Before Dose 1, 1 month post-Dose 2 (group Fx017-mFxD only), before and 1 month post-Dose 3, before and 1 month after Dose 4, before and 1 month after each yearly dose and at Month 50
Day 0-Month 50
During 30-day follow up period after each dose of study vaccine
During 7-day follow up period after each dose of study vaccine
During 30-day follow up period after each dose of study vaccine
Before Dose 3, 7 days post-Dose 3, 30 days post-Dose 3
During the 7-day (Days 0-6) follow-up period after each vaccination

Secondary end point(s): The occurrence of clinical malaria meeting the primary and secondary case definitions
The occurrence of incident P. falciparum infections
The prevalence of P. falciparum infections defined by positive blood slide at each cross-sectional survey
Number of seropositive subjects for anti-CS antibodies and anti-HBs antibodies, antibody concentrations for anti-CS and anti-HBs (in a sub-cohort of first 25 subjects enrolled in each group per site)
Number of subjects with any, fatal and related SAEs, with any AE and SAE leading to withdrawal from further vaccination, with severe malaria, cerebral malaria, potential Immune mediated diseases (pIMDs), meningitis
Number of subjects with seizures
Number of subjects with generalized convulsive seizures
Number of subjects with any unsolicited AE(s)
Number of subjects with abnormal laboratory values (in a sub-cohort of first 25 subjects enrolled in each group per site)
Number of subjects with any solicited local and general symptoms (in the reactogenity sub-cohort of first 25 subjects en-rolled per site)

Secondary ID(s)

204889

Source(s) of Monetary Support

Program for Appropriate Technology in Health (PATH)

GlaxoSmithKline Biologicals