Infant Malaria Vaccine Schedule Optimization

PATH

Status and phase

Enrolling

Phase 2

Conditions

Malaria Vaccines

Treatments

Biological: Yellow Fever vaccine

Biological: R21 Matrix-M (R21/MM) Malaria Vaccine

Biological: Placebo

Biological: Rotavirus, Live Attenuated (Oral) Vaccine

Biological: Meningococcal A conjugate vaccine

Biological: Pneumococcal Polysaccharide Conjugate Vaccine

Biological: Typhoid Conjugate vaccine

Biological: Measles and Rubella Vaccine

Biological: Hexavalent Vaccine

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT06879327

CVIA 108

Details and patient eligibility

About

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.

Full description

The R21/Matrix-M (R21/MM) vaccine has been recommended by the World Health Organization (WHO) to prevent clinical malaria in young children living in moderate to high transmission areas of Sub-Saharan Africa. R21/MM is based on the circumsporozoite protein (CSP) targeting the pre-erythrocytic stage of Plasmodium falciparum. R21/MM elicits high levels of antibodies against the central repeat (Asn-Ala-Asn-Pro [NANP]) of the circumsporozoite protein (CSP) which has been shown to correlate with protection. Currently, R21/MM is recommended to be delivered to young children starting at 5-6 months of age with 3 doses given at monthly intervals, however, there are no existing Essential Programme on Immunization (EPI) vaccine visits scheduled at these ages.

We plan to evaluate, using the R21/MM malaria vaccine as a model system, how age at first vaccine dose and time intervals between doses modify the immunogenicity of the vaccine and the ensuant efficacy in protecting infants against clinical Plasmodium falciparum malaria.

Healthy male or female infants 6 to 7 weeks of age will be randomized to one of three different immunization schedule cohorts: a) a "compressed" conventional schedule at 6-10-14 weeks of age; b) a "relaxed" schedule at 2-4-6 months of age; c) a "relaxed" schedule at 3-6-9 months of age. Participants in each immunization schedule cohort will be randomized in a ratio of 3:1 to receive 4 doses of either R21/MM or placebo with a 4th dose to be administered at 15 months of age.

Infants randomized to the respective immunization schedule categories will receive co-administered routine EPI vaccines. The study will include the provision of a three dose R21/MM compressed schedule to all participants randomized to the placebo arms upon completion of the study at Month 27 of life.

Enrollment

1,200 estimated patients

Sex

All

Ages

42 to 49 days old

Volunteers

Accepts Healthy Volunteers

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

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-height/length 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.

Trial design

Primary purpose

Prevention

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

1,200 participants in 6 patient groups, including a placebo group

Compressed 6-10-14 Week Schedule: R21/MM Malaria Vaccine

Experimental group

Description:

Participants will receive R21/MM malaria vaccination at 6, 10, and 14 weeks of age, co-administered with hexavalent vaccine, pneumococcal conjugate vaccine (PCV), and oral rotavirus vaccine (RV). At 9 months of age participants will receive measles-rubella (MR) vaccine, yellow fever (YF) vaccine, and typhoid conjugate vaccine (TCV). Participants will receive a booster dose of R21/MM malaria vaccine at 15 months of age co-administered with the 2nd dose of measles-rubella vaccine and meningococcal A conjugate vaccine (MenA).

Treatment:

Biological: Hexavalent Vaccine

Biological: Typhoid Conjugate vaccine

Biological: Measles and Rubella Vaccine

Biological: Pneumococcal Polysaccharide Conjugate Vaccine

Biological: Meningococcal A conjugate vaccine

Biological: Rotavirus, Live Attenuated (Oral) Vaccine

Biological: R21 Matrix-M (R21/MM) Malaria Vaccine

Biological: Yellow Fever vaccine

Compressed 6-10-14 Week Schedule: Placebo

Placebo Comparator group

Description:

Participants will receive placebo at 6, 10, and 14 weeks of age, co-administered with hexavalent vaccine, PCV, and oral RV. At 9 months of age participants will receive MR and YF vaccines, and TCV. Participants will receive a booster dose of placebo at 15 months of age co-administered with the 2nd dose of MR vaccine and MenA vaccine. Participants will receive R21/MM malaria vaccination at 27, 28, and 29 months of age (after completion of the study).

Treatment:

Biological: Hexavalent Vaccine

Biological: Typhoid Conjugate vaccine

Biological: Measles and Rubella Vaccine

Biological: Pneumococcal Polysaccharide Conjugate Vaccine

Biological: Meningococcal A conjugate vaccine

Biological: Rotavirus, Live Attenuated (Oral) Vaccine

Biological: Placebo

Biological: Yellow Fever vaccine

Relaxed 2-4-6 Month Schedule: R21/MM Malaria Vaccine

Experimental group

Description:

Participants will receive R21/MM malaria vaccination at 2, 4, and 6 months of age co-administered with hexavalent vaccine, PCV, and oral RV. At 9 months of age participants will receive MR and YF vaccines and TCV. Participants will receive a booster dose of R21/MM malaria vaccine at 15 months of age co-administered with the 2nd dose of MR vaccine and MenA vaccine.

Treatment:

Biological: Hexavalent Vaccine

Biological: Typhoid Conjugate vaccine

Biological: Measles and Rubella Vaccine

Biological: Pneumococcal Polysaccharide Conjugate Vaccine

Biological: Meningococcal A conjugate vaccine

Biological: Rotavirus, Live Attenuated (Oral) Vaccine

Biological: R21 Matrix-M (R21/MM) Malaria Vaccine

Biological: Yellow Fever vaccine

Relaxed 2-4-6 Month Schedule: Placebo

Placebo Comparator group

Description:

Participants will receive placebo at 2, 4, and 6 months of age co-administered with hexavalent vaccine, PCV, and oral RV. At 9 months of age participants will receive MR and YF vaccines, and TCV. Participants will receive a booster dose of placebo at 15 months of age co-administered with the 2nd dose of MR vaccine and MenA vaccine. Participants will receive R21/MM malaria vaccination at 27, 28, and 29 months of age (after completion of the study).

Treatment:

Biological: Hexavalent Vaccine

Biological: Typhoid Conjugate vaccine

Biological: Measles and Rubella Vaccine

Biological: Pneumococcal Polysaccharide Conjugate Vaccine

Biological: Meningococcal A conjugate vaccine

Biological: Rotavirus, Live Attenuated (Oral) Vaccine

Biological: Placebo

Biological: Yellow Fever vaccine

Relaxed 3-6-9 Month Schedule: R21/MM Malaria Vaccine

Experimental group

Description:

Participants will receive R21/MM malaria vaccination at 3, 6, and 9 months of age. Participants will receive the hexavalent vaccine, PCV, and oral RV at 6 weeks, 10 weeks, and 3 months of age. At 9 months of age participants will receive MR and YF vaccines and TCV. Participants will receive a booster dose of R21/MM malaria vaccine at 15 months of age co-administered with the 2nd dose of MR vaccine and the MenA vaccine.

Treatment:

Biological: Hexavalent Vaccine

Biological: Typhoid Conjugate vaccine

Biological: Measles and Rubella Vaccine

Biological: Pneumococcal Polysaccharide Conjugate Vaccine

Biological: Meningococcal A conjugate vaccine

Biological: Rotavirus, Live Attenuated (Oral) Vaccine

Biological: R21 Matrix-M (R21/MM) Malaria Vaccine

Biological: Yellow Fever vaccine

Relaxed 3-6-9 Month Schedule: Placebo

Placebo Comparator group

Description:

Participants will receive placebo at 3, 6, and 9 months of age. Participants will receive the hexavalent vaccine, PCV, and oral RV at 6 weeks, 10 weeks, and 3 months of age. At 9 months of age participants will receive MR and YF vaccines and TCV. Participants will receive a booster dose of placebo at 15 months of age co-administered with the 2nd dose of MR vaccine and the MenA vaccine. Participants will receive R21/MM malaria vaccination at 27, 28, and 29 months of age (after completion of the study).

Treatment:

Biological: Hexavalent Vaccine

Biological: Typhoid Conjugate vaccine

Biological: Measles and Rubella Vaccine

Biological: Pneumococcal Polysaccharide Conjugate Vaccine

Biological: Meningococcal A conjugate vaccine

Biological: Rotavirus, Live Attenuated (Oral) Vaccine

Biological: Placebo

Biological: Yellow Fever vaccine