Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201905692900706 Date of Approval: 14/05/2019
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
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
Official scientific 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
Brief summary describing the background and objectives of the trial 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
Type of trial RCT
Acronym (If the trial has an acronym then please provide) Mal 094
Disease(s) or condition(s) being studied Infections and Infestations,Paediatrics
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 28/09/2017
Actual trial start date 28/09/2017
Anticipated date of last follow up 19/06/2020
Actual Last follow-up date 15/12/2022
Anticipated target sample size (number of participants) 1500
Actual target sample size (number of participants) 1500
Recruitment status Active, not recruiting
Publication URL https://clinicaltrials.gov/ct2/show/NCT03276962?term=204889&rank=2.
Secondary Ids Issuing authority/Trial register
NCT03276962 clinicaltrials.gov
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group R012 20 Group full doses of 0.5ml Month 0, Month 1, Month 2 and a full dose at Month 20 Subjects will receive intramuscular injection of RTS,S/AS01E (full dose: 0.5 ml). 300
Experimental Group R012 14 mD Group full dose: 0.5 ml. Month 0, Month 1, Month 2 and yearly full doses at Month 14, Month 26, Month 38. Subjects will receive intramuscular injection of RTS,S/AS01E (full dose: 0.5 ml). 300
Experimental Group Fx012 14 mFxD Group full dose: 0.5 ml. Month 0, Month 1 and RTS,S/AS01E 1/5th dose at Month 2, Month 14, Month 26, Month 38. Subjects will receive a full dose intramuscular injection 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. full dose: 0.5 ml while 1/5th dose: 0.1 ml. 300
Experimental Group Fx017 mFxD Group Full dose: 0.5 ml while 1/5th dose: 0.1 ml. Month 0, Month 1 and RTS,S/AS01E 1/5th dose at Month 7, Month 20, Month 32. Subjects will receive a full dose of RTS,S/AS01E intramuscular injection at Month 0, Month 1 and RTS,S/AS01E 1/5th dose at Month 7, Month 20, Month 32. 300
Control Group Control Group 0.1 ml. Month 0, Month 1, Month 2 Subjects will receive intramuscular injection of rabies vaccine (0.1 ml). 300 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
•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 •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 Infant: 13 Month(s)-24 Month(s) 5 Month(s) 17 Month(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 28/09/2017 Western Institutional Review Board
Ethics Committee Address
Street address City Postal code Country
39th Avenue SE Suite 120 Puyallup WA 98374-2115 Puyallup Washington 1019 United States of America
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 27/08/2017 Food Drug Authority Ghana
Ethics Committee Address
Street address City Postal code Country
Cantonments Accra Ghana Accra 2783 Ghana
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 08/02/2017 School of Medical Sciences Komfo Anokye Teaching Hospital Committee on Human Research Publication Ethics
Ethics Committee Address
Street address City Postal code Country
Kwame Nkrumah University of Science and Technology College of Health Sciences Kumasi 0000 Ghana
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 30/05/2017 Ghana Health Service Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
Research and Development Division Ghana Health Service Accra 0000 Ghana
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 13/03/2018 Centre for Disease Control Human Research Protection Office Instiutional Review Board
Ethics Committee Address
Street address City Postal code Country
Clifton Road Atlanta Atlanta 1600 United States of America
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 06/03/2018 Pharmacy and Poisons Board Expert Committee on Clinical Trials
Ethics Committee Address
Street address City Postal code Country
Pharmacy and Poisons Board House Lenana Road Nairobi 40100 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 11/01/2018 KEMRI Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
Nairobi Nairobi 00100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 1.The occurrence of clinical malaria meeting the primary case definition. 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. From Month 2.5 up to Month 14
Secondary Outcome 1.The occurrence of clinical malaria meeting the primary and secondary case definitions. 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. From Day 0 up to Month 50
Secondary Outcome 2.The occurrence of incident P. falciparum infections. Vaccine efficacy against incident P. falciparum infections defined by positive blood slide. From Day 0 to Month 50
Secondary Outcome 3.The prevalence of P. falciparum infections defined by positive blood slide at each cross-sectional survey. Prevalence of P. falciparum infections of each RTS,S/AS01E schedule at cross-sectional visits. Monthly from Month 0-20 and every three months thereafter till Month 50
Secondary Outcome 4.Number of seropositive subjects for anti-CS antibodies (in a sub-cohort of first 25 subjects enrolled in each group per site). A seropositive subject is defined as a subject with antibody concentrations ≥ 0.5 EU/mL 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). Before Dose 1 to Month 50 as detailed above
Secondary Outcome 5.Number of seropositive subjects for anti-HBs antibodies (in a sub-cohort of first 25 subjects enrolled in each group per site. A seropositive subject is defined as a subject with antibody concentrations ≥ 10 mIU/mL 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). Before Dose 1 and Month 50 as detailed above
Secondary Outcome 6.Antibody concentrations for anti-CS (in a sub-cohort of first 25 subjects enrolled in each group per site). Concentrations are expressed as geometric mean concentrations. 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) Before Dose 1 and Month 50 as detailed above
Secondary Outcome 7.Antibody concentrations for anti-HBs. (in a sub-cohort of first 25 subjects enrolled in each group per site). Concentrations are expressed as geometric mean concentrations. 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). Before Dose 1 and Month 50 as detailed above
Secondary Outcome 8.Number of subjects with any, fatal and related SAEs. SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. From Day 0 to Month 50.
Secondary Outcome 9.Number of subjects with any AE and SAE leading to withdrawal from further vaccination. 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. From Day 0 to Month 50.
Secondary Outcome 10.Number of subjects with severe malaria and cerebral malaria. 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 From Day 0 to Month 50.
Secondary Outcome 11.Number of subjects with potential Immune mediated diseases (pIMDs). 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. From Day 0 to Month 50.
Secondary Outcome 12.Number of subjects with meningitis. The number of subjects with meningitis per study group. From Day 0 to Month 50.
Secondary Outcome 13.Number of subjects with of seizures. The number of subjects with seizures per study group. During the 30-day (Days 0-29) follow up period after each dose of study vaccine. Days 0-29 follow up period after each dose of study vaccine.
Secondary Outcome 14.Number of subjects with generalized convulsive seizures. The number of subjects with generalized convulsive seizures per study group. During the 7-day (Days 0-6) follow up period after each dose of study vaccine Days 0-6 follow up period after each dose of study vaccine.
Secondary Outcome 15.Number of subjects with any unsolicited AE(s). 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. During the 30-day (Days 0-29) follow up period after each dose of study vaccine. Days 0-29 follow up period after each dose of study vaccine.
Secondary Outcome 16.Number of subjects with abnormal laboratory values. (in a sub-cohort of first 25 subjects enrolled in each group per site). The assessed parameters will be summarised by toxicity grading scales and by group. Before Dose 3, seven days post-Dose 3 and 30 days post-Dose 3
Secondary Outcome 17.Number of subjects with any solicited local and general symptoms. (in the reactogenity sub-cohort of first 25 subjects enrolled per site) Solicited local symptoms assessed will be pain, redness and swelling. Solicited general symptoms assessed will be drowsiness, fever, irritability/fussiness and loss of appetite. During the 7-day (Days 0-6) follow-up period after each vaccination. Days 0-6 follow-up period after each vaccination.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Malaria Research Centre P.O.Box 27 Agogo Ghana
Kenya Medical Research Institute Centre for Global Health Off Kisumu-Busia Road Kisumu Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
GlaxoSmithKline Biologicals Rue de lInstitut 89 1330 Rixensart Belgium
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor GlaxoSmithKline Biologicals Rue de lInstitut 89 1330 Rixensart Belgium Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Clinical Disclosure Advisor GSKClinicalSupportHD@gsk.com 0018773793718 Rue de l Institut, 89
City Postal code Country Position/Affiliation
Rixensart 1330 Ghana Clinical Disclosure Advisor
Role Name Email Phone Street address
Scientific Enquiries Clinical Disclosure Advisor GSKClinicalSupportHD@gsk.com 0018773793718 Rue de l Institut, 89
City Postal code Country Position/Affiliation
Rixensart 1330 Belgium Clinical Disclosure Advisor
Role Name Email Phone Street address
Public Enquiries Clinical Disclosure Advisor GSKClinicalSupportHD@gsk.com 0018773793718 Rue de l Institut, 89
City Postal code Country Position/Affiliation
Rixensart 1330 Belgium Clinical Disclosure Advisor
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site. Clinical Study Report This will be based on the time frame set out on www.clinicalstudydatarequest.com This will be based on the criteria set out on www.clinicalstudydatarequest.com
URL Results Available Results Summary Result Posting Date First Journal Publication Date
www.clinicalstudydatarequest.com No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
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