Malaria
Conditions
Interventions
Normal saline
Sponsors
PATH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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. 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. For infants in Cohort 2, randomization to receive vaccine dose 1 (Groups 3 and 4 of R21/MM or placebo, respectively) will occur at 2 months (56-63 days of age). For infants in Cohort 3, randomization to receive vaccine dose 1 (Groups 5 and 6 of R21/MM or placebo, respectively) will occur at 3 months (84-91 days of age). - The participant’s parent/guardian must be willing to avoid travel, particularly in the 28 days after each study vaccination, must confirm willingness to contact the study team in the event of unexpected/unavoidable travel and, for the safety cohort, must confirm availability for the home visits to be conducted by a field worker to collect solicited AEs over the 7 days (day of vaccination and 6 subsequent days) following each study vaccine. - The participant’s parent/guardian must confirm willingness to bring their child to the study clinic / local health care clinic, and capacity to contact the study team in the event the subject has any illnesses or other health concerns during the study. - Participants who the investigator believes that their parent/guardian can and will comply with the requirements of the protocol (e.g. return for follow-up visits) may be enrolled in the study.
Exclusion criteria
Exclusion criteria: - Acute disease at the time of enrolment (acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to participants with a minor illness such as diarrhea, mild upper respiratory infection, without low-grade febrile illness, i.e. axillary temperature < 37.5°C). - 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-age Z score of less than -3 or other clinical signs of malnutrition. - Infant with major congenital defects. -The infant has anaemia associated with clinical signs of symptoms of decompensation, or a haemoglobin of = 5.0 g/dL. - History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. - Any confirmed or suspected immunosuppressive or immunodeficient state (including HIV or asplenia) or known maternal HIV infection (no HIV testing will be routinely done by the study team). - Administration of immunoglobulins and/or any blood products/blood transfusion from birth to time of planned administration of the vaccine candidate. - Previous vaccination of participant or biological mother with a malaria vaccine. - Participation in another research study involving receipt of an investigational product or planned use during the study period. - Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.Geometric mean titers (GMTs) of anti-CS NANP IgG at baseline and 28 days after 3rd vaccine dose for each immunization schedule category. 2.Ratio of anti-CS NANP GMTs 28 days after R21/MM 3rd vaccine dose for infants in i) 3-6-9 month to 2-4-6 month schedule; ii) 3-6-9 month to 6- 10-14 week schedule; iii) 2-4-6 month to 6-10-14 week schedule. 3.Geometric mean fold rise (GMFR) in anti-CS NANP IgG 28 days after 3rd vaccine dose compared to baseline anti-CS NANP concentrations in each immunization schedule category. 4.Geometric mean titers (GMTs) of anti-CS NANP IgG at baseline and 28 days after 3rd vaccine dose for each immunization schedule category. 5.Ratio of anti-CS NANP GMTs 28 days after R21/MM 3rd vaccine dose for infants in i) 3-6-9 month to 2-4-6 month schedule; ii) 3-6-9 month to 6- 10-14 week schedule; iii) 2-4-6 month to 6-10-14 week schedule. 6.Geometric mean fold rise (GMFR) in anti-CS NANP IgG 28 days after 3rd vaccine dose compared to baseline anti-CS NANP concentrations in each immunization schedule category. ;1.Local (redness, swelling, and pain at the injection site) and Systemic (fever, drowsiness, irritability, decreased appetite) reactions. 2.Unsolicited Adverse events (AEs) 3.Serious adverse events (SAEs) 4.Adverse Events of Special Interest (AESI) ;1.Geometric mean titers (GMTs) of anti-CS NANP IgG at baseline and 28 days after 3rd vaccine dose for each immunization schedule category. 2.Ratio of anti-CS NANP GMTs 28 days after R21/MM 3rd vaccine dose for infants in i) 3-6-9 month to 2-4-6 month schedule; ii) 3-6-9 month to 6- 10-14 week schedule; iii) 2-4-6 month to 6-10-14 week schedule. 3.Geometric mean fold rise (GMFR) in anti-CS NANP IgG 28 days after 3rd vaccine dose compared to baseline anti-CS NANP concentrations in | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Geometric mean titers (GMTs) of anti-CS NANP IgG before and 28 days after 4th vaccine dose in each of the three different immunization schedule categories. 2. Ratio of anti-CS NANP GMTs 28 days after 4th R21/MM vaccine dose for infants in i) 3-6-9 month to 2-4-6 month schedule; ii) 3-6-9 month to 6-10-14 week schedule; iii) 2-4-6 month to 6-10-14 week schedule. 3. Fold increase in anti-CS NANP titer post 4th dose compared to pre-4th dose for in each of the three different immunization schedule categories. ;1a. The incidence rate ratio of multiple malaria episodes in R21-immunized and placebo participants meeting the primary case definition beginning at 6 weeks of age (randomization) to Month 27 in infants randomized in each of the three different immunization schedule categories. 1b. The incidence rate ratio of multiple malaria episodes in R21-immunized and placebo participants meeting the primary case definition beginning at 6 weeks of age (randomization) to Month 15 in infants randomized in each of the three different immunization schedule categories. 1c. The incidence rate ratio of multiple malaria episodes in R21-immunized and placebo participants meeting the primary case definition beginning at 2 weeks post dose 4 to Month 27 in infants randomized in each of the three different immunization schedule categories. 2a. The incidence rate ratio of multiple malaria episodes in R21-immunized and placebo participants meeting the secondary case definition beginning at 6 weeks of age (randomization) to Month 27 in infants randomized in each of the three different immunization schedule categories | — |
Countries
Burkina Faso
Contacts
Public ContactMichael;Michael Thigpen;Thigpen
Senior Medical Officer Clinical Functional Area Path;Senior Medical Officer Clinical Functional Area Path
Outcome results
None listed