Safety and Immunogenicity of GSK Biologicals' Malaria Vaccine 257049 When Administered on 7 Schedules to African Infants

Malaria Clinical Trial

Official title:

Safety and Immunogenicity of GSK Biologicals' Candidate Malaria Vaccine 257049 When Administered on Different Schedules to Infants in Africa

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01231503
• Other study ID #: 111315
• Status: Completed
• Phase: Phase 2
• Start date: January 13, 2011
• Est. completion date: December 23, 2014

Study information

• Verified date: June 2018
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the malaria vaccine program of the MVI/GSK partnership is to develop an efficacious malaria vaccine that is deliverable through the existing system, the Expanded Program on Immunization (EPI) of WHO. This study has been designed to:

• Investigate the safety and immunogenicity of 7 infant immunization schedules of the experimental malaria vaccine integrated with an EPI regimen.

• Investigate how to maximize the antibody response to the experimental malaria vaccine.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 480
• Est. completion date: December 23, 2014
• Est. primary completion date: April 30, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 7 Days

Eligibility

Inclusion Criteria:

All subjects must satisfy the following criteria at study entry:

• A male or female infant between 1 and 7 days (inclusive) of age (where day 1 is day of birth).

• Signed or thumb-printed informed consent obtained from the parent(s)/guardian(s) of the child. Where parent(s)/guardian(s) are illiterate, the consent form will be countersigned by a witness.

• Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol (e.g. return for follow-up visits) should be enrolled in the study.

• Born to a mother negative for HIV antibody and Hepatitis B surface antigen.

• Subjects who are born after a normal gestation period (between 37 and 42 weeks) (Gestational age will be determined by carrying out a clinical assessment on infants according to the principles set out by Dubowitz (1970) in the first 5 days of life).

• A minimum weight of 2.5 kg.

Exclusion Criteria:

The following criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study:

• Acute or chronic illness determined by clinical or physical examination and laboratory screening tests including, but not limited to:

• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

• A family history of congenital or hereditary immunodeficiency.

• Major congenital defects.

• History of any neurological disorders or seizures.

• Laboratory screening tests out of normal ranges/limits defined per protocol.

• Previous vaccination with diphtheria, tetanus, pertussis (whole-cell or acellular), Hemophilus influenzae type b, hepatitis B, BCG tuberculosis, measles or oral polio vaccines.

• Planned administration/administration of a licensed vaccine (i.e. a vaccine that is approved by one of the following authorities: FDA or EU member state or WHO [with respect to prequalification]) not foreseen by the study protocol within 7 days of the first dose of study vaccine.

• Administration of immunoglobulins, blood transfusions or other blood products since birth to the first dose of study vaccine or planned administration during the study period.

• Use of a drug or vaccine that is not approved for that indication (by one of the following authorities: FDA or EU member state or WHO [with respect to prequalification]) other than the study vaccine starting at birth or planned use during the study period.

• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.

• Simultaneous participation in any other clinical trial.

• Same-sex twins (to avoid misidentification).

• Maternal death.

• 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 vaccine.

• Children will not be enrolled if any maternal, obstetrical or neonatal event that has occurred might, in the judgment of the investigator, result in increased neonatal/infant morbidity

• Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.

Related Conditions & MeSH terms

• Malaria

Intervention

Biological:
• GSK Biological's Investigational Malaria Vaccine 257049
3 doses, intramuscular (IM) route, in left antero-lateral thigh, as follows: 1) RTS,S Neo-10-14 Group at less than (=<) 7 days, at 10 and 14 weeks (wks) of age; 2) RTS,S Neo-10-26 Group =< 7 days, at 10 and 26 wks of age; 3) RTS,S 6-10-14 Group at 6, 10 and 14 wks of age; 4) RTS,S 6-10-26 Group at 6, 10 and 26 wks of age; 5) Engerix-B Neo/RTS,S 6-10-26 Group at 6, 10 and 26 wks of age; 6) RTS,S 10-14-26 Group at 10, 14 and 26 wks of age; 7) RTS,S 14-26-9M Group at 14 and 26 wks of age and at 9 months of age
• Engerix-B
1 dose, intramuscular route: left antero-lateral thigh at birth (=< 7 days of age)
• Tritanrix HepB Hib
3 doses, intramuscular route: right antero-lateral thigh at 6, 10 and 14 weeks of age
• BCG
1 dose, intradermal route, in shoulder at birth (=< 7 days of age)
• OPV
4 doses, orally, at birth (=< 7 days of age) and at 6, 10 and 14 weeks of age
• Rouvax
1 dose, intramuscular (IM) route, in left antero-lateral thigh, at 9 months of age

Locations

Country	Name	City	State
Malawi	GSK Investigational Site	Bangwe, Blantyre

Sponsors (2)

Lead Sponsor	Collaborator
GlaxoSmithKline	The PATH Malaria Vaccine Initiative (MVI)

Country where clinical trial is conducted

Malawi, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)	Month 18 immunogenicity data were tertiary objectives, and although not required to be disclosed were included in this result summary at the request of the study team to show the full study immunogenicity results.	At Month 18 post vaccination
Other	Anti-Hepatitis B Surface Antibody (Anti-HBs) Concentrations	Month 18 immunogenicity data were tertiary objectives, and although not required to be disclosed were included in this result summary at the request of the study team to show the full study immunogenicity results.	At Month 18 post vaccination
Primary	Number of Subjects Reported With Serious Adverse Events (SAEs)	An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or may evolve into one of the outcomes listed above. "Any" is defined an incidence of a SAE regardless of intensity/severity.	From study start at Month 0 up to Month 10.
Primary	Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)	Anti-CS antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off for the endpoint was a GMC value greater than or equal to (=) 0.5 EL.U/mL.	At 1 month (M) post Dose 3 of RTS,S/AS01E, e. a. M5 for RTS,S Neo-10-14, RTS,S 6-10-14 and Engerix-B Neo groups
Primary	Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)	Anti-CS antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off for the endpoint was a GMC value greater than or equal to (=) 0.5 EL.U/mL.	At 1 month (M) post Dose 3 of RTS,S/AS01E, e. a. M7 for RTS,S Neo-10-26, RTS,S 6-10-26, Engerix-B Neo/RTS,S 6-10-26, and RTS,S 10-14-26 groups
Primary	Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)	Anti-CS antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off for the endpoint was a GMC value greater than or equal to (=) 0.5 EL.U/mL.	At 1 month (M) post Dose 3 of RTS,S/AS01E, e. a. M10 for RTS,S 14-26-9M Group
Secondary	Number of Subjects Reported With Unsolicited Adverse Events (AEs)	An AE is 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. "Any" is defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. Please note that, for this outcome measure, analysis was performed only on subjects with at least one administered dose of RTS,S/AS01E and/or DTPwHepB/Hib for the Engerix-B Neo Group.	During the 30-day (Days 0-29) post vaccination period following 3 doses of RTS,S/AS01E versus DTPwHepB/Hib for the Engerix-B Neo Group
Secondary	Number of Subjects Reported With Serious Adverse Events (SAEs)	An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or may evolve into one of the outcomes listed above. "Any" is defined an incidence of a SAE regardless of intensity/severity.	From study start at Month 0 up to Month 18 (corresponding data lock point =23 March 2015)
Secondary	Number of Subjects Reported With Biochemical Abnormalities, for the Alanine Aminotransferase (ALT) Parameter	This outcome measure concerns biochemical abnormalities, for the alanine aminotransferase (ALT) parameter. Subjects' levels were assessed as either normal, Grade 1, Grade 2, Grade 3, Grade 4 or Missing. Normal ALT level was defined as ALT< 60 International units per milliliter (IU/mL). Grade 1 ALT level was defined as 1.1 to 2.5 times the upper limit of normal (ULN). Grade 2 ALT level was defined as 2.6 to 5.0 times the ULN. Grade 3 ALT level was defined as 5.1 to 10.0 times the ULN. Grade 4 ALT level was defined as > 10.0 times the ULN.	At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).
Secondary	Number of Subjects Reported With Biochemical Abnormalities, for the Creatinine (CREA) Parameter	This outcome measure concerns biochemical abnormalities, for the creatinine (CREA) parameter. Subjects' levels were assessed as either normal, Grade 1, Grade 2, Grade 3, Grade 4 or Missing. Normal CREA level was defined as CREA = 106, 88 and 71 micromoles per liter (µmol/L) for subjects 1, 2 or = 2 days of age, respectively. Grade 1 CREA level was defined as 1.1 to 1.3 times the upper limit of normal (ULN). Grade 2 CREA level was defined as 1.4 to 1.8 times the ULN. Grade 3 CREA level was defined as 1.9 to 3.4 times the ULN. Grade 4 CREA level was defined as = 3.5 times the ULN.	At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).
Secondary	Number of Subjects Reported With Haematological Abnormalities, for the Haemoglobin (HAE) Parameter	This outcome measure concerns haematological abnormalities, for the haemoglobin (HAE) parameter. Subjects' levels were assessed as either normal, Grade (G) 1, G 2, G 3, G 4 or Missing. Normal HAE level was defined as HAE > 13.0 and 10.5 grams per deciliter (g/dL) for subjects aged 1 to 21 and 22 to 35 days respectively. Grades were defined as follows: 1) In subjects aged 1 to 21 days: G1 = HAE as 12.0 to 13.0 g/dL, G2 = HAE as 10.0 to 11.9 g/dL, G3 = HAE as 9.0 to 9.9 g/dL, G4 = HAE < 9.0 g/dL; 2) In subjects aged 22 to 35 days: G1 = HAE as 9.5 to 10.5 g/dL, G2 = HAE as 8.0 to 9.4 g/dL, G3 = HAE as 7.0 to 7.9 g/dL, G4 = HAE < 7.0 g/dL; 3) In subjects aged 36 to 56 days: G1 = HAE as 8.5 to 9.4 g/dL, G2 = HAE as 7.0 to 8.4 g/dL, G3 = HAE as 6.0 to 6.9 g/dL, G4 = HAE < 6.0 g/dL; 4) In subjects aged = 57 days: G1 = HAE as 10.0 to 10.9 g/dL, G2 = HAE as 9.0 to 9.9 g/dL, G3 = HAE as 7.0 to 8.9 g/dL, G4 = HAE < 7.0 g/dL.	At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).
Secondary	Number of Subjects Reported With Haematological Abnormalities, for the Platelets (PLA) Parameter	This outcome measure concerns haematological abnormalities, for the platelets (PLA) parameter. Subjects' levels were assessed as either normal, Grade (G) 1, G2, G3, G4 or Missing. Normal PLA level was defined as > 125 x 10 exp 9 PLA per liter (Billions PLA/L). Grade 1 PLA level was defined as 100 to 125 Billions PLA/L. Grade 2 PLA level was defined as 50 to 99 Billions PLA/L. Grade 3 PLA level was defined as 25 to 49 Billions PLA/L. Grade 4 PLA level was defined as < 25 Billions PLA/L.	At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).
Secondary	Number of Subjects Reported With Haematological Abnormalities, for the White Blood Cells (WBC) Parameter	This outcome measure concerns haematological abnormalities, for the white blood cells (WBC) parameter. Subjects' levels were assessed as either normal, Grade 1, Grade 2, Grade 3, Grade 4 or Missing. Normal WBC level was defined as > 2.5 x 10 exp 9 WBC per liter (Billions WBC/L). Grade 1 WBC level was defined as 2.0 to 2.5 Billions WBC/L. Grade 2 WBC level was defined as 1.5 to 1.999 Billions WBC/L. Grade 3 WBC level was defined as 1.0 to 1.499 Billions WBC/L. Grade 4 WBC level was defined as < 1.0 Billions WBC/L.	At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).
Secondary	Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)	Anti-CS antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value for the assay was greater than or equal to (=) 0.5 EL.U/mL.	At Screening (SCR), at Month (M) 4, at M5, at M7 and/or at M10, according to the vaccination scheduling for the specific group assessed concerned group
Secondary	Anti-Hepatitis B Surface Antibody (Anti-HBs) Concentrations.	Concentrations, by enzyme-linked immunosorbent assay (ELISA), were presented as geometric mean concentrations (GMCs), and expressed in milli-international units per milliliter (mIU/mL). The seropositivity and seroprotection cut-off values for the assay were greater than or equal to (=) 6.2 and 10 mIU/mL, respectively.	At Screening (SCR), at Month 5 (M5), at Month 7 (M7) and at Month 10 (M10), according to the vaccination scheduling
Secondary	Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations	Anti-D and anti-TT antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in International units per milliliter (IU/mL), and tabulated. The seropositivity cut-off value for the assay was = 0.1 IU/mL.	At Month 5
Secondary	Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations	Anti-PRP antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in microgram per milliliter (µg/mL), and tabulated. The seroprotection cut-off value for the assay was = 0.15 µg/mL.	At Month 5
Secondary	Anti-polio Type 1, 2 and 3 (Anti-Polio 1, 2 and 3) Antibody Concentrations	Anti-Polio 1, 2 and 3 antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in international units per mililiter (IU/mL) and tabulated. The seroprotection cut-off value for the assay was = 8 IU/mL.	At Month 5
Secondary	Concentrations of Antibodies Against Acellular B-pertussis (BPT)	Concentrations of anti-BPT antibodies were determined by enzyme-linked immunosorbent assay (ELISA) and expressed as geometric mean concentrations (GMCs), in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value for the assay was = 15 EL.U/mL.	At Month 5
Secondary	Concentrations of Antibodies Against Measles Antigens	Concentrations of anti measles antibodies were determined by ELISA and expressed as GMCs in milli-international units per millilitre (mIU/mL).; The seropositivity cut-off value for the assay was = 150 mIU/mL. Please note that this outcome measure was only assessed in subjects in the RTS,S 14-26-9M and Engerix-B Neo groups.	At Month 10
Secondary	Number of Subjects Reported With Solicited Local Symptoms	Solicited local symptoms assessed include pain, redness and swelling. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity.	Within 7 days (Days 0-6) after Week 0 vaccination
Secondary	Number of Subjects Reported With Solicited Local Symptoms	Solicited local symptoms assessed include pain, redness and swelling. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity.	Within 7 days (Days 0-6) after Week 6 vaccination
Secondary	Number of Subjects Reported With Solicited Local Symptoms	Solicited local symptoms assessed include pain, redness and swelling. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity.	Within 7 days (Days 0-6) after Week 10 vaccination
Secondary	Number of Subjects Reported With Solicited Local Symptoms	Solicited local symptoms assessed include pain, redness and swelling. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity.	Within 7 days (Days 0-6) after Week 14 vaccination
Secondary	Number of Subjects Reported With Solicited Local Symptoms	Solicited local symptoms assessed include pain, redness and swelling. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity. RTS,S Neo-10-14 Group, RTS,S 6-10-14 Group and Engerix-B Neo Group didn't receive vaccination at this time point.	Within 7 days (Days 0-6) after Week 26 vaccination
Secondary	Number of Subjects Reported With Solicited Local Symptoms	Solicited local symptoms assessed include pain, redness and swelling. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity.	Within 7 days (Days 0-6) after Month 9 vaccination
Secondary	Number of Subjects Reported With Solicited General Symptoms	Solicited general symptoms assessed include Drowsiness, Fever (temperature by axillary route = 37.5°C), Irritability/Fussiness and Loss of appetite. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity or relationship to vaccination.	Within 7 days (Days 0-6) after Week 0 vaccination
Secondary	Number of Subjects Reported With Solicited General Symptoms	Solicited general symptoms assessed include Drowsiness, Fever (temperature by axillary route = 37.5°C), Irritability/Fussiness and Loss of appetite. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity or relationship to vaccination.	Within 7 days (Days 0-6) after Week 6 vaccination
Secondary	Number of Subjects Reported With Solicited General Symptoms	Solicited general symptoms assessed include Drowsiness, Fever (temperature by axillary route = 37.5°C), Irritability/Fussiness and Loss of appetite. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity or relationship to vaccination.	Within 7 days (Days 0-6) after Week 10 vaccination
Secondary	Number of Subjects Reported With Solicited General Symptoms	Solicited general symptoms assessed include Drowsiness, Fever (temperature by axillary route = 37.5°C), Irritability/Fussiness and Loss of appetite. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity or relationship to vaccination.	Within 7 days (Days 0-6) after Week 14 vaccination
Secondary	Number of Subjects Reported With Solicited General Symptoms	Solicited general symptoms assessed include Drowsiness, Fever (temperature by axillary route = 37.5°C), Irritability/Fussiness and Loss of appetite. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity or relationship to vaccination. RTS,S Neo-10-14 Group, RTS,S 6-10-14 Group and Engerix-B Neo Group didn't receive any vaccination at this time point	Within 7 days (Days 0-6) after Week 26 vaccination
Secondary	Number of Subjects Reported With Solicited General Symptoms	Solicited general symptoms assessed include Drowsiness, Fever (temperature by axillary route = 37.5°C), Irritability/Fussiness and Loss of appetite. "Any" about a specific symptom is defined as incidence of this symptom, regardless of its intensity or relationship to vaccination.	Within 7 days (Days 0-6) after Month 9 vaccination

External Links

•   IPD for this study will be made available via the Clinical Study Data Request site.