Safety and Immunogenicity of RH5.1/Matrix-M in Adults and Infants Living in Tanzania

NCT ID: NCT04318002

Last Updated: 2024-11-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-21
• Study Completion Date: 2023-08-27

Brief Summary

This is an age de-escalation, dose-escalation open label randomised trial studying the safety and immunogenicity of RH5.1/Matrix-M, administered intramuscularly in healthy adults, young children and infants in Tanzania

Detailed Description

A total of 60 participants will be enrolled consisting of healthy adults (18-45 years) and infants (5-17 months) residing in Bagamoyo district, Tanzania. Participants will be recruited from areas of low malaria transmission in Bagamoyo town and areas of high malaria transmission within Bagamoyo district. All participants will be followed for 2-2.5years after the first vaccination with RH5.1/Matrix-M vaccination. The duration of the entire study will be 2-2.5years per participant from the time of first vaccination.

The trial is funded by EDCTP (reference: RIA2016V-1649 MMVC).

The paper containing this trial's results is available at: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00312-8/fulltext

Conditions

Malaria,Falciparum

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Group 1A

Volunteers (aged 18-45 years) of low malaria exposure status will receive 3 doses of 10µg RH5.1 /50µg Matrix-M intramuscularly at months 0, 1 and 2

Group Type: EXPERIMENTAL

RH5.1/Matrix-M

Intervention Type: BIOLOGICAL

3 doses of RH5.1/Matrix-M at different concentrations: RH5.1(10µg)/Matrix-M (50µg), RH5.1(50µg)/ Matrix-M (50µg), RH5.1(10µg)/ Matrix-M (25µg), RH5.1(50µg)/ Matrix-M (25µg)

Group 1B

Volunteers (aged 18-45 years) of low malaria exposure status will receive 2 doses of 50µg RH5.1 /50µg Matrix-M intramuscularly at months 0, 1 and 1 dose of 10µg RH5.1 /50µg Matrix-M at month 6.

Group Type: EXPERIMENTAL

RH5.1/Matrix-M

Intervention Type: BIOLOGICAL

3 doses of RH5.1/Matrix-M at different concentrations: RH5.1(10µg)/Matrix-M (50µg), RH5.1(50µg)/ Matrix-M (50µg), RH5.1(10µg)/ Matrix-M (25µg), RH5.1(50µg)/ Matrix-M (25µg)

Group 2A

Volunteers (aged 5-17 months) of low malaria exposure status will receive 3 doses of 10µg RH5.1 /50µg Matrix-M intramuscularly at months 0, 1 and 2.

Group Type: EXPERIMENTAL

RH5.1/Matrix-M

Intervention Type: BIOLOGICAL

3 doses of RH5.1/Matrix-M at different concentrations: RH5.1(10µg)/Matrix-M (50µg), RH5.1(50µg)/ Matrix-M (50µg), RH5.1(10µg)/ Matrix-M (25µg), RH5.1(50µg)/ Matrix-M (25µg)

Group 2B

Volunteers (aged 5-17 months) of low malaria exposure status will receive 3 doses of 10µg RH5.1 /50µg Matrix-M intramuscularly at months 0, 1 and 6.

Group Type: EXPERIMENTAL

RH5.1/Matrix-M

Intervention Type: BIOLOGICAL

3 doses of RH5.1/Matrix-M at different concentrations: RH5.1(10µg)/Matrix-M (50µg), RH5.1(50µg)/ Matrix-M (50µg), RH5.1(10µg)/ Matrix-M (25µg), RH5.1(50µg)/ Matrix-M (25µg)

Group 2C

Volunteers (aged 5-17 months) of low malaria exposure status will receive 2 doses of 50µg RH5.1 /50µg Matrix-M intramuscularly at months 0, 1 and 1 dose of 10µg RH5.1 /50µg Matrix-M at month 6.

Group Type: EXPERIMENTAL

RH5.1/Matrix-M

Intervention Type: BIOLOGICAL

3 doses of RH5.1/Matrix-M at different concentrations: RH5.1(10µg)/Matrix-M (50µg), RH5.1(50µg)/ Matrix-M (50µg), RH5.1(10µg)/ Matrix-M (25µg), RH5.1(50µg)/ Matrix-M (25µg)

Group 2D

Volunteers (aged 5-17 months) of high malaria exposure status will receive 2 doses of 50µg RH5.1 /50µg Matrix-M intramuscularly at months 0, 1 and 1 dose of 10µg RH5.1 /50µg Matrix-M at month 6.

Group Type: EXPERIMENTAL

RH5.1/Matrix-M

Intervention Type: BIOLOGICAL

3 doses of RH5.1/Matrix-M at different concentrations: RH5.1(10µg)/Matrix-M (50µg), RH5.1(50µg)/ Matrix-M (50µg), RH5.1(10µg)/ Matrix-M (25µg), RH5.1(50µg)/ Matrix-M (25µg)

Interventions

RH5.1/Matrix-M

3 doses of RH5.1/Matrix-M at different concentrations: RH5.1(10µg)/Matrix-M (50µg), RH5.1(50µg)/ Matrix-M (50µg), RH5.1(10µg)/ Matrix-M (25µg), RH5.1(50µg)/ Matrix-M (25µg)

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Group 1: Healthy male or female adults aged 18-45 years at the time of enrolment with signed consent.
• Group 1 (Female only participants): Must be non-pregnant (as demonstrated by a negative urine pregnancy test), and practice continuous effective contraception* for the duration of the study. (Female volunteers are required to use an effective form of contraception during the course of the study as this is a Phase I, study and there is currently no information about the effect of this vaccine on a foetus. Acceptable forms of contraception for female volunteers include:
• Established use of oral, injected or implanted hormonal methods of contraception.
• Placement of an intrauterine device (IUD) or intrauterine system (IUS).
• Total abdominal hysterectomy.
• Groups 2a, 2b, 2c & 2d: Healthy male or female infants aged 5-17 months at the time of enrolment with signed consent obtained from parents or guardians.
• Planned long-term (at least 24 months from the date of recruitment) or permanent residence in the study area.
• Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2; or infants with Z-score of weight- for-age within ±2SD.

Exclusion Criteria

• Clinically significant congenital abnormalities as judged by the PI or other delegated individual.
• Clinically significant history of skin disorder (psoriasis, contact dermatitis etc.), allergy, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease and neurological illness as judged by the PI or other delegated individual.
• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed).
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
• Weight for age z-scores below 2 standard deviations of normal for age.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, e.g. egg products, Kathon, neomycin, betapropiolactone.
• Any history of anaphylaxis in relation to vaccination.
• Clinically significant laboratory abnormality as judged by the PI or other delegated individual.
• Blood transfusion within one month of enrolment.
• History of vaccination with previous experimental malaria vaccines.
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
• Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period.
• Seropositive for hepatitis B surface antigen (HBsAg) or hepatitis C (HCV IgG).
• Any other finding which in the opinion of the PI or other delegated individual would increase the risk of an adverse outcome from participation in the trial.
• Likelihood of travel away from the study area.
• Positive malaria by blood smear at screening.
• Female participant who is pregnant, lactating or planning pregnancy during the course of the trial.
• Scheduled elective surgery or other procedures requiring general anaesthesia during the trial.
• Any other significant disease, disorder or situation 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, or the participant's ability to participate in the trial.

• Minimum Eligible Age: 5 Months
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ifakara Health Institute

OTHER

Sponsor Role: collaborator

European and Developing Countries Clinical Trials Partnership (EDCTP)

OTHER_GOV

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ally Olotu

Role: PRINCIPAL_INVESTIGATOR

Ifakara Health Institute

Locations

Ifakara Health Institute Clinical Trial Facility

Bagamoyo, , Tanzania

Countries

Tanzania

References

Silk SE, Kalinga WF, Salkeld J, Mtaka IM, Ahmed S, Milando F, Diouf A, Bundi CK, Balige N, Hassan O, Mkindi CG, Rwezaula S, Athumani T, Mswata S, Lilolime NS, Simon B, Msami H, Mohamed M, David DM, Mohammed L, Nyaulingo G, Mwalimu B, Juma O, Mwamlima TG, Sasamalo IA, Mkumbange RP, Kamage JJ, Barrett JR, King LDW, Hou MM, Pulido D, Carnrot C, Lawrie AM, Cowan RE, Nugent FL, Roberts R, Cho JS, Long CA, Nielsen CM, Miura K, Draper SJ, Olotu AI, Minassian AM. Blood-stage malaria vaccine candidate RH5.1/Matrix-M in healthy Tanzanian adults and children; an open-label, non-randomised, first-in-human, single-centre, phase 1b trial. Lancet Infect Dis. 2024 Oct;24(10):1105-1117. doi: 10.1016/S1473-3099(24)00312-8. Epub 2024 Jun 13.

Reference Type: DERIVED

PMID: 38880111 (View on PubMed)

Mwamlima TG, Mwakasungula SM, Mkindi CG, Tambwe MM, Mswata SS, Mbwambo SG, Mboya MF, Draper SJ, Silk SE, Mpina MG, Vianney JM, Olotu AI. Understanding the role of serological and clinical data on assessing the dynamic of malaria transmission: a case study of Bagamoyo district, Tanzania. Pan Afr Med J. 2022 Oct 7;43:60. doi: 10.11604/pamj.2022.43.60.35779. eCollection 2022.

Reference Type: DERIVED

PMID: 36578806 (View on PubMed)

Other Identifiers

VAC080

Identifier Type: -

Identifier Source: org_study_id