Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04318002
Recruitment Status : Not yet recruiting
First Posted : March 23, 2020
Last Update Posted : March 23, 2020
Sponsor:
Collaborator:
Ifakara Health Institute
Information provided by (Responsible Party):
University of Oxford

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

Condition or disease Intervention/treatment Phase
Malaria,Falciparum Biological: RH5.1/Matrix-M Phase 1

Detailed Description:
A total of 60 participants will be enrolled consisting of healthy adults (18-45 years) and infants (6-11 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 districts and surrounding districts. 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase Ib Clinical Trial to Assess the Safety and Immunogenicity of the Blood-stage Plasmodium Falciparum Malaria Vaccine Candidate RH5.1/Matrix-M in Healthy Adults and Infants in Tanzania
Estimated Study Start Date : April 2020
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: 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
Biological: 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)

Experimental: 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 6.5.
Biological: 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)

Experimental: Group 2A
Volunteers (aged 6-11 months) of low malaria exposure status will receive 3 doses of 10µg RH5.1 /25µg Matrix-M intramuscularly at months 0, 1 and 2.
Biological: 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)

Experimental: Group 2B
Volunteers (aged 6-11 months) of low malaria exposure status will receive 3 doses of 10µg RH5.1 /25µg Matrix-M intramuscularly at months 0, 1 and 6.5.
Biological: 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)

Experimental: Group 2C
Volunteers (aged 6-11 months) of low malaria exposure status will receive 2 doses of 50µg RH5.1 /25µg Matrix-M intramuscularly at months 0, 1 and 1 dose of 10µg RH5.1 /25µg Matrix-M at month 6.5.
Biological: 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)

Experimental: Group 2D
Volunteers (aged 6-11 months) of high malaria exposure status will receive 2 doses of 50µg RH5.1 /25µg Matrix-M intramuscularly at months 0, 1 and 1 dose of 10µg RH5.1 /25µg Matrix-M at month 6.5.
Biological: 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)




Primary Outcome Measures :
  1. 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. [ Time Frame: Assessment of solicited symptoms in the first 7 days post vaccination ]
    Occurrence of solicited symptoms after each vaccination during a 7-day surveillance period.

  2. 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. [ Time Frame: Assessment of unsolicited symptoms in the first 30 days post vaccination ]
    Occurrence of unsolicited symptoms after each vaccination during a 28-day surveillance period (day of vaccination and 28 subsequent days).

  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 serious adverse events. [ Time Frame: Assessment of SAEs until the end of the study (approx 2 years) ]
    Occurrence of serious adverse events throughout the study period.


Secondary Outcome Measures :
  1. Anti-RH5 antibody concentration by ELISA [ Time Frame: Through study completion (approx 2 years) ]
    Evaluation of the magnitude of antibody responses to RH5 in adults, children and infants residing in a malaria endemic country, as measured by ELISA

  2. Growth inhibition activity of IgG from vaccinees on a panel of P. falciparum parasites [ Time Frame: Through study completion (approx 2 years) ]
    Evaluation of the quality of antibody responses to RH5 in adults, children and infants residing in a malaria endemic country, as measured by an assay of growth inhibition activity on the vaccinees' sera

  3. Avidity of anti-RH5 antibodies by ELISA and/or other assays (to be defined) [ Time Frame: Through study completion (approx 2 years) ]
    Evaluation of the avidity of antibody responses to RH5 in adults, children and infants residing in a malaria endemic country, as measured by ELISA

  4. Cellular immune responses to the RH5 by ELISpot assay and/or Flow cytommetry [ Time Frame: Through study completion (approx 2 years) ]
    Evaluation of the magnitude and quality of cellular immune responses to PfRH5 in adults, children and infants residing in a malaria endemic country, by ELISpot assay and/or Flow cytommetry



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Months to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Groups 2a, 2b, 2c & 2d: Healthy male or female infants aged 6-11 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04318002


Contacts
Layout table for location contacts
Contact: Angela Minassian +44865611425 angela.minassian@ndm.ox.ac.uk
Contact: Ally Olotu +255718927104 aolotu@ihi.or.tz

Locations
Layout table for location information
Tanzania
Ifakara Health Institute Clinical Trial Facility
Bagamoyo, Tanzania
Contact: Ally Olotu    +255718927104    aolotu@ihi.or.tz   
Sponsors and Collaborators
University of Oxford
Ifakara Health Institute
Investigators
Layout table for investigator information
Principal Investigator: Ally Olotu Ifakara Health Institute
Layout table for additonal information
Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT04318002    
Other Study ID Numbers: VAC080
First Posted: March 23, 2020    Key Record Dates
Last Update Posted: March 23, 2020
Last Verified: February 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Oxford:
Vaccine
Additional relevant MeSH terms:
Layout table for MeSH terms
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases