Assessment of Safety and Immunogenicity of a Single Vial Presentation of R21/Matrix-M and Co-Administration With EPI Vaccines

Phase 1

Active, not recruiting

• Conditions: Malaria
• Interventions: Biological: R21/Matrix-M - single vial formulation; Biological: Licensed vaccine - Measles-rubella; Biological: R21/Matrix-M - two vial formulation; Biological: Licensed vaccine - Pentavalent (diphtheria, tetanus, pertussis, hepatitis B and Hib); Biological: Licensed vaccine - Yellow fever; Biological: Licensed vaccine - Oral Polio Vaccine (OPV); Biological: Licensed vaccine - Rotavirus; Biological: Licensed vaccine - Pneumococcal vaccine; Biological: Licensed vaccine - Inactivated Polio Vaccine (IPV)

• Registration Number: NCT05155579
• Lead Sponsor: University of Oxford

Brief Summary

This is a Phase Ib trial conducted in Bougouni, Mali to evaluate the safety and immunogenicity of R21/Matrix-M in a single and two vial presentation, with different immunisation schedules, and when co-administered with EPI vaccines in African children.

Detailed Description

This trial has six groups. This will be a double-blind, individually randomised trial, with 1:1 randomisation with the single or two vial presentation of R21/Matrix-M malaria vaccine for study groups 1, 2 and 3. Groups 1, 2 and 3 are to assess the safety and immunogenicity of R21/Matrix-M as a single vial formulation compared with a two-vial formulation, in children aged 5- 36 months, in a malaria endemic area. The age range of 5-36 months has been split into three groups to ensure an even age spread across age groups.

For groups 4 and 5, this is a randomised, open-label study to assess the safety and immunogenicity of R21/Matrix-M when co-administrated with various EPI vaccines at the relevant ages, in a malaria endemic area.

Group 6 is a randomised, open-label study to assess safety and immunogenicity of a delayed, third dose of R21/Matrix-M in 5-36 month old children, in a malaria endemic area.

For groups 1, 2, 3, 5 and 6, participants will be randomised 1:1. For group 4, participants will be randomised 3:3:1.

Approximately 590 children will be recruited across these six study groups.

The primary study objectives are:

Safety

* To assess the safety and reactogenicity of R21/Matrix-M, as a single- vial formulation in 5-36-month old African children.

* To assess the safety and reactogenicity of co-administration of R21/Matrix-M with the EPI vaccines given at 9 months, measles-rubella and yellow fever vaccines, in African children.

* To assess the safety and reactogenicity of co-administration of R21/Matrix-M with the EPI vaccines given at 6, 10 and 14 weeks of age, pentavalent and oral polio vaccine (OPV), in African children.

Immunogenicity

* To assess the immunogenicity of R21/Matrix-M, as a single- vial formulation in 5-36-month-old African children, compared with the two-vial formulation.

* To assess the immunogenicity of EPI vaccines given at 9 months, measles-rubella and yellow fever vaccines, when given with and without R21/Matrix-M

* To assess the immunogenicity of EPI vaccines given at 6, 10 and 14 weeks of age, pentavalent and oral polio vaccines, given as part of EPI at 6, 10 and 14 weeks of age, when given with and without R21/Matrix-M.

The secondary study objectives are:

* To assess the safety and reactogenicity of R21/Matrix-M, as a single- vial formulation in African children compared with the two-vial formulation.

* To assess the safety and reactogenicity of a delayed third dose of R21/Matrix-M in 5-36-month-old African children.

* To assess the immunogenicity of a delayed third dose of R21/Matrix-M in 5-36-month-old African children.

This trial is funded by the Serum Institute of India.

Study Timeline

• Study First Submitted: 2021-12-09
• Study First Submitted QC: 2021-12-09
• Study First Posted: 2021-12-13
• Study Start: 2022-05-14
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-15
• Last Update Posted: 2024-05-16
• Primary Completion: 2025-05
• Study Completion: 2025-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 590

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 4a	R21/Matrix-M - single vial formulation	150 participants, aged 6-7 months at the time of randomisation (to ensure third vaccination is given at approximately 9 months), who will receive 3 doses of 5µg R21/50µg Matrix-M one month apart. At the time of the third dose they will receive their measles-rubella and yellow fever vaccinations at the same time as R21/Matrix-M.
Group 4b	Licensed vaccine - Measles-rubella	150 participants, aged 6-7 months at the time of randomisation, who will receive a measles-rubella and yellow fever vaccination 2 months after randomisation.
Groups 1a, 2a and 3a	R21/Matrix-M - two vial formulation	60 children, aged 5-36 months, who will receive 4 doses of 5µg R21/50µg Matrix-M as a two vial formulation. The first three doses will be given one month apart, followed by a booster vaccination 12 months after the third dose. The age range of 5-36 months has been split into three groups to ensure an even age spread across age groups. Group 1a is 20 children aged 5-11 months, group 2a is 20 children aged 12-23 months, and group 3a is 20 children aged 24-36 months.
Group 1b, 2b and 3b	R21/Matrix-M - single vial formulation	60 children, aged 5-36 months, who will receive 4 doses of 5µg R21/50µg Matrix-M as a single vial formulation. The first three doses will be given one month apart, followed by a booster vaccination 12 months after the third dose. The age range of 5-36 months has been split into three groups to ensure an even age spread across age groups. Group 1b is 20 children aged 5-11 months, group 2b is 20 children aged 12-23 months, and group 3b is 20 children aged 24-36 months.
Group 4a	Licensed vaccine - Yellow fever	150 participants, aged 6-7 months at the time of randomisation (to ensure third vaccination is given at approximately 9 months), who will receive 3 doses of 5µg R21/50µg Matrix-M one month apart. At the time of the third dose they will receive their measles-rubella and yellow fever vaccinations at the same time as R21/Matrix-M.
Group 5a	Licensed vaccine - Pneumococcal vaccine	30 children who will receive 3 doses of 5µg R21/50µg Matrix-M, pentavalent, rotavirus, pneumococcal and OPV vaccines at 6, 10 and 14 weeks of age. They will receive IPV two weeks following the third dose.
Group 5b	Licensed vaccine - Pentavalent (diphtheria, tetanus, pertussis, hepatitis B and Hib)	30 children who will receive 3 doses of pentavalent, rotavirus, pneumococcal and OPV vaccines at 6, 10 and 14 weeks of age. They will receive IPV two weeks following the third dose.
Group 5b	Licensed vaccine - Pneumococcal vaccine	30 children who will receive 3 doses of pentavalent, rotavirus, pneumococcal and OPV vaccines at 6, 10 and 14 weeks of age. They will receive IPV two weeks following the third dose.
Group 4a	Licensed vaccine - Measles-rubella	150 participants, aged 6-7 months at the time of randomisation (to ensure third vaccination is given at approximately 9 months), who will receive 3 doses of 5µg R21/50µg Matrix-M one month apart. At the time of the third dose they will receive their measles-rubella and yellow fever vaccinations at the same time as R21/Matrix-M.
Group 4b	Licensed vaccine - Yellow fever	150 participants, aged 6-7 months at the time of randomisation, who will receive a measles-rubella and yellow fever vaccination 2 months after randomisation.
Group 4c	R21/Matrix-M - single vial formulation	Group 4c is 50 participants, aged 6-7 months at the time of randomisation, who will receive 3 doses of 5µg R21/50µg Matrix-M one month apart.
Group 5a	Licensed vaccine - Pentavalent (diphtheria, tetanus, pertussis, hepatitis B and Hib)	30 children who will receive 3 doses of 5µg R21/50µg Matrix-M, pentavalent, rotavirus, pneumococcal and OPV vaccines at 6, 10 and 14 weeks of age. They will receive IPV two weeks following the third dose.
Group 5a	Licensed vaccine - Rotavirus	30 children who will receive 3 doses of 5µg R21/50µg Matrix-M, pentavalent, rotavirus, pneumococcal and OPV vaccines at 6, 10 and 14 weeks of age. They will receive IPV two weeks following the third dose.
Group 5a	Licensed vaccine - Inactivated Polio Vaccine (IPV)	30 children who will receive 3 doses of 5µg R21/50µg Matrix-M, pentavalent, rotavirus, pneumococcal and OPV vaccines at 6, 10 and 14 weeks of age. They will receive IPV two weeks following the third dose.
Group 6b	R21/Matrix-M - single vial formulation	30 children, aged 5-36 months, who will receive 3 doses of 5µg R21/50µg Matrix-M. The first two doses one month apart and the third dose 12 months after the first dose.
Group 5a	R21/Matrix-M - single vial formulation	30 children who will receive 3 doses of 5µg R21/50µg Matrix-M, pentavalent, rotavirus, pneumococcal and OPV vaccines at 6, 10 and 14 weeks of age. They will receive IPV two weeks following the third dose.
Group 5b	Licensed vaccine - Rotavirus	30 children who will receive 3 doses of pentavalent, rotavirus, pneumococcal and OPV vaccines at 6, 10 and 14 weeks of age. They will receive IPV two weeks following the third dose.
Group 5a	Licensed vaccine - Oral Polio Vaccine (OPV)	30 children who will receive 3 doses of 5µg R21/50µg Matrix-M, pentavalent, rotavirus, pneumococcal and OPV vaccines at 6, 10 and 14 weeks of age. They will receive IPV two weeks following the third dose.
Group 5b	Licensed vaccine - Oral Polio Vaccine (OPV)	30 children who will receive 3 doses of pentavalent, rotavirus, pneumococcal and OPV vaccines at 6, 10 and 14 weeks of age. They will receive IPV two weeks following the third dose.
Group 6a	R21/Matrix-M - single vial formulation	30 children, aged 5-36 months, who will receive 3 doses of 5µg R21/50µg Matrix-M. The first two doses one month apart and the third dose 6 months after the first dose.
Group 5b	Licensed vaccine - Inactivated Polio Vaccine (IPV)	30 children who will receive 3 doses of pentavalent, rotavirus, pneumococcal and OPV vaccines at 6, 10 and 14 weeks of age. They will receive IPV two weeks following the third dose.

Primary Outcome Measures

Name	Time	Method
Safety	2 years	Solicited adverse events: * Occurrence of solicited local reactogenicity signs and symptoms for 7 days following the vaccination.; * Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following the vaccination.; Unsolicited adverse events; * Occurrence of unsolicited adverse events for 28 days following the vaccination. Laboratory adverse events; * Change from baseline for safety laboratory measures thought to be clinically significant.; Serious adverse events; • Occurrence of serious adverse events for the whole study duration.
Immunogenicity	2 years	* To assess the humoral immunogenicity of R21/Matrix-M as a single- vial formulation in 5-36-month-old African children, compared with the two-vial formulation, 0, 30, 180 and 365 days after the administration of the third dose of R21/Matrix-M; and 0, 30, 180 and 365 days after the administration of a booster dose.; * To assess the humoral immunogenicity of EPI vaccines given at 9 months, measles-rubella and yellow fever vaccines, when given with and without R21/Matrix-M, 0, 30, 180 and 360 days after the administration of the third dose of R21/Matrix-M; * To assess the humoral immunogenicity of EPI vaccines given at 6, 10 and 14 weeks of age, pentavalent and oral polio vaccines, given as part of EPI at 6, 10 and 14 weeks of age, when given with and without R21/Matrix-M, 0, 30, 180 and 360 days after the administration of the third dose of R21/Matrix-M or the EPI vaccines.

Secondary Outcome Measures

Name	Time	Method
Immunogenicity of a delayed third dose	2 years	• To assess the humoral immunogenicity of a delayed third dose of R21/Matrix-M in 5-36-month-old African children, at 30 and 180 days after administration of the second dose, and 0, 30, 180 and 360 days after the administration of the third dose of R21/Matrix-M
Safety of a delayed third dose	2 years	Solicited adverse events: * Occurrence of solicited local reactogenicity signs and symptoms for 7 days following the vaccination.; * Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following the vaccination.; Unsolicited adverse events; * Occurrence of unsolicited adverse events for 28 days following the vaccination. Laboratory adverse events; * Change from baseline for safety laboratory measures thought to be clinically significant.; Serious adverse events; • Occurrence of serious adverse events for the whole study duration.

Trial Locations

Locations (2)

CCVTM, University of Oxford; 🇬🇧 Oxford, United Kingdom

Malaria Research & Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Dentistry, University of Sciences Techniques and Technologies of Bamako; 🇲🇱 Bamako, Mali