Infant Malaria Vaccine Schedule Optimization
ConditionMalaria Vaccines
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age42-49
SponsorPATH
About this trial
The aim of this study is to identify an optimal infant vaccine schedule for a malaria vaccine which is better aligned with the timing of other vaccine interventions.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Signed informed consent or thumb-printed and witnessed informed consent obtained from the parent/legal guardian of the infant.
Infants must have been born full-term (at ≥37 weeks of gestation) and > 2500 grams at birth.
Immunization schedule Cohorts 1, 2, and 3: Male and female infants 42-49 days (inclusive) of age at time of enrollment.
Prior to group randomization, for infants in Cohort 1 randomization to receive vaccine dose 1 (Groups 1 and 2 of R21/MM or placebo, respectively) will occur at 42-49 days of age. Infants in Cohorts 2 and 3 will not be randomized to R21/MM or placebo; placebo will no longer be given. Rather infants in these cohorts will receive open-label R21/MM according to the immunization schedule category to which they have been randomized. Infants in Cohort 2, will receive their open-label R21/MM vaccine dose 1 (Group 3) at 2 months (56-63 days of age). Infants in Cohort 3, will receive their open-label R21/MM vaccine dose 1 (Group 5) at 3 months (84-91 days of age).
Disqualifiers
Clinically significant pulmonary, cardiovascular, gastrointestinal, endocrine, neurological, skin, hepatic or renal functional abnormality, as determined by medical history, physical examination or laboratory tests which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial.
At time of enrollment, any infant who has received any dose of the hexavalent/pentavalent vaccines, pneumococcal vaccine, rotavirus vaccine, IPV or has received more than one dose of oral polio virus or more than one dose of hepatitis B vaccine.
Weight-for-length/height Z score of less than -3 or other clinical signs of malnutrition.
Infant with major congenital defects.
Trial design
Design model
Parallel
Treatments tested in this trial
R21 Matrix-M (R21/MM) Malaria Vaccine
Biological/VaccineAdministered by intramuscular injection. Each 0.5 mL dose contains R21 Malaria Antigen (5 mcg) and Matrix-M1 (Adjuvant) (50 mcg).
Placebo
Biological/VaccineAdministered by intramuscular injection. Each dose (0.5 mL) contains Normal saline (0.9%).
Hexavalent Vaccine
Biological/VaccineAdministered by intramuscular injection. Each dose of 0.5 mL contains: * Diphtheria Toxoid \> 30 IU * Tetanus Toxoid \> 40 IU * B. pertussis (whole cell) \> 4 IU * Hepatitis B surface antigen (HBsAg) (recombinant DNA) 15 mcg * Inactivated polio vaccine (Salk strains grown on vero cells): Type - 1 (Mahoney strain) 40 D antigen units (DU); Type - 2 (MEF-1 strain) 8 DU; Type - 3 (Saukett strain) 32 DU * Haemophilus influenzae Type b (Hib) Conjugate Vaccine (Adsorbed) polyribosylribitol phosphate (PRP) 10 mcg conjugated to tetanus toxoid (TT) (carrier protein) 19 to 33 mcg\]
Pneumococcal Polysaccharide Conjugate Vaccine
Biological/VaccineAdministered by intramuscular injection. Each 0.5 mL dose contains 2 mcg each Saccharide for serotypes 1, 5, 9V, 14, 19A, 19F, 23F, 7F, 6A and 4 mcg Saccharide for serotype 6B.
Rotavirus, Live Attenuated (Oral) Vaccine
Biological/VaccineAdministered orally. Each 2.0 mL dose contains: Live Attenuated Bovine-Human Rotavirus Reassortant \[G1, G2, G3, G4 and G9\], 5.6 focus-forming units (FFU) / serotype.
Measles and Rubella Vaccine
Biological/VaccineAdministered by subcutaneous injection. Each 0.5 mL dose contains not less than 1000 cell culture infectious dose 50% (CCID50) of Measles virus and 1000 CCID50 of Rubella virus.
Meningococcal (A, C, Y, W, X) polysaccharide conjugate vaccine
Biological/VaccineAdministered by intramuscular injection. Each 0.5 mL dose contains 5 mcg of each Meningococcal A, C, Y, W, and X polysaccharide, 7.8 to 33.4 mcg of TT and 11.7 to 50.1 mcg of recombinant CRM197.
Yellow Fever vaccine
Biological/VaccineYellow fever vaccine will be locally sourced by each trial site in accordance with the countries' EPI program.
Typhoid Conjugate vaccine
Biological/VaccineTyphoid conjugate vaccine will be locally sourced by each trial site in accordance with the countries' EPI program.
Treatment groups
964 Participants
are divided into 4 treatment groupsGroup A: Compressed 6-10-14 Week Schedule: R21/MM Malaria VaccineExperimental treatment 8 interventions
Group B: Compressed 6-10-14 Week Schedule: Placebo / Recommended 5-6-7 Month Schedule: R21/MM Malaria VaccineOther 9 interventions
Group C: Relaxed 2-4-6 Month Schedule: R21/MM Malaria VaccineExperimental treatment 8 interventions
Group D: Relaxed 3-6-9 Month Schedule: R21/MM Malaria VaccineExperimental treatment 8 interventions
Trial outcomes
Primary outcomes
1
Geometric Mean Titers (GMTs) of Anti-circumsporozoite (CS) Immunoglobulin G (IgG) at Baseline and 28 Days after 3rd Vaccine Dose
The anti-CS antibody responses elicited following the primary 3-dose schedule of R21/MM will be assessed in the "compressed" (6-10-14 week) immunization schedule and the two "relaxed" (2-4-6 month and 3-6-9 month) immunization schedule cohorts.
Time frame
Baseline and 28 days after 3rd vaccine dose2
Geometric Mean Fold Rise (GMFR) in Anti-CS IgG 28 Days after 3rd Vaccine Dose Compared to Baseline
The anti-CS antibody responses elicited following the primary 3-dose schedule of R21/MM will be assessed in the "compressed" (6-10-14 week) immunization schedule and the two "relaxed" (2-4-6 month and 3-6-9 month) immunization schedule cohorts.
Time frame
Baseline and 28 days after 3rd vaccine dose3
Number of Participants with Solicited Adverse Events
Local (redness, swelling, and pain at the injection site) and systemic (fever, drowsiness, irritability, decreased appetite) reactions will be collected in a subset of participants (the first 40 participants in each immunization schedule category at each site).
Time frame
7 days after each study vaccination4
Number of Participants with Unsolicited Adverse Events
Time frame
28 days after each study vaccinationSecondary outcomes
1
Geometric Mean Titers (GMTs) of Anti-CS IgG Before and 28 Days After 4th Vaccine Dose
The anti-CS antibody responses elicited following the 4th dose of R21/MM will be assessed in the "compressed" (6-10-14 week) immunization schedule and the two "relaxed" (2-4-6 month and 3-6-9 month) immunization schedule cohorts.
Time frame
Month 15 predose and 28 days after vaccination2
GMFR in Anti-CS IgG Titer Post 4th Dose Compared to Pre-4th Dose
The anti-CS antibody responses elicited following the 4th dose of R21/MM will be assessed in the "compressed" (6-10-14 week) immunization schedule and the two "relaxed" (2-4-6 month and 3-6-9 month) immunization schedule cohorts.
Time frame
Month 15 predose and 28 days after 4th doseSponsors and contacts
Click on the lead sponsor to view all of their trials.
PATH
Lead sponsor
Pharmassist Ltd
Collaborator
Serum Institute of India Pvt. Ltd.
Collaborator
Agilis
Collaborator
MCT-CRO
Collaborator
Cytespace
Collaborator
Source ClinicalTrials.gov