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

NCT04318002 | Completed Phase 1 DMC

• 1 other identifier: VAC080
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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

Conditions

Malaria,Falciparum

Keywords

Vaccine

Outcome Measures

Primary Outcomes (3)

• Safety of RH5.1-Matrix-M given in 3 doses in healthy Tanzanian adults and children naturally exposed to malaria as assessed by the occurrence of solicited symptoms.

  Occurrence of solicited symptoms after each vaccination during a 7-day surveillance period.

  Assessment of solicited symptoms in the first 7 days post vaccination

• Safety of RH5.1-Matrix-M given in 3 doses in healthy Tanzanian adults and children naturally exposed to malaria as assessed by the occurrence of unsolicited symptoms.

  Occurrence of unsolicited symptoms after each vaccination during a 28-day surveillance period (day of vaccination and 28 subsequent days).

  Assessment of unsolicited symptoms in the first 30 days post vaccination

• Safety of RH5.1-Matrix-M given in 3 doses in healthy Tanzanian adults and children naturally exposed to malaria as assessed by the occurrence of serious adverse events.

  Occurrence of serious adverse events throughout the study period.

  Assessment of SAEs until the end of the study (approx 2 years)

Secondary Outcomes (4)

• Anti-RH5 antibody concentration by ELISA

  Through study completion (approx 2 years)

• Growth inhibition activity of IgG from vaccinees on a panel of P. falciparum parasites

  Through study completion (approx 2 years)

• Avidity of anti-RH5 antibodies by ELISA and/or other assays (to be defined)

  Through study completion (approx 2 years)

• Cellular immune responses to the RH5 by ELISpot assay and/or Flow cytommetry

  Through study completion (approx 2 years)

Study Arms (6)

Group 1A

EXPERIMENTAL

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

Biological: RH5.1/Matrix-M

Group 1B

EXPERIMENTAL

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.

Biological: RH5.1/Matrix-M

Group 2A

EXPERIMENTAL

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.

Biological: RH5.1/Matrix-M

Group 2B

EXPERIMENTAL

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.

Biological: RH5.1/Matrix-M

Group 2C

EXPERIMENTAL

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.

Biological: RH5.1/Matrix-M

Group 2D

EXPERIMENTAL

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.

Biological: RH5.1/Matrix-M

Interventions

RH5.1/Matrix-M 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 1A; Group 1B; Group 2A; Group 2B; Group 2C; Group 2D

Eligibility Criteria

• Age: 5 Months - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Oxford: lead
• Ifakara Health Institute: collaborator
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator

Study Sites (1)

Ifakara Health Institute Clinical Trial Facility

Bagamoyo, Tanzania

Location

Related Publications (2)

• 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.

  PMID: 38880111 DERIVED

• 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.

  PMID: 36578806 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Ally Olotu

  Ifakara Health Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2020
• First Posted: March 23, 2020
• Study Start: January 21, 2021
• Primary Completion: August 27, 2023
• Study Completion: August 27, 2023
• Last Updated: November 22, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: After publication of manuscripts related to the trial and for a minimum of 15 years from the end of the trial.
• Access Criteria: Anonymized participant data will be made available when the trial is complete, upon requests directed to a corresponding author. Proposals will be reviewed and approved by the sponsor, investigators, and collaborators on the basis of scientific merit. After approval of a proposal, data can be shared through the secure online repository.

Locations

TA (1)