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Safety, Immunogenicity and Efficacy of R21 Matrix-M in 5-17 Month Old Children in Nanoro, Burkina Faso

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ClinicalTrials.gov Identifier: NCT03896724
Recruitment Status : Recruiting
First Posted : April 1, 2019
Last Update Posted : July 2, 2019
Sponsor:
Collaborator:
European Commission
Information provided by (Responsible Party):
University of Oxford

Brief Summary:
This is a double blind randomised controlled clinical trial to evaluate the efficacy of R21 adjuvanted with Matrix-M in healthy 5-17 month old children in a malaria endemic area.

Condition or disease Intervention/treatment Phase
Malaria,Falciparum Biological: R21 adjuvanted with 25mcg Matrix-M Biological: Rabies Vaccine Biological: R21 adjuvanted with 50mcg Matrix-M Phase 1 Phase 2

Detailed Description:

Participants will be randomised 2:1 to receive vaccination with the IMP (R21 adjuvanted with Matrix-M; Group 1) or control vaccination with Rabies Vaccine (Group 2). Participants and investigators will be blinded to group allocation for each participant. Efficacy of vaccination will be assessed by comparing the development of malaria between Groups 1 versus Group 2 participants.

There are two study vaccines: the IMP, R21 adjuvanted with Matrix-M; and Rabies Vaccine. Group 1 (active vaccine group) participants will receive 3 vaccinations of R21 5μg with 50μg Matrix-M, 4 weeks apart via the intramuscular route.

Group 2 (control group) participants will receive three vaccinations with rabies vaccine, four weeks apart, all given intramuscularly.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase Ib/IIb Randomised Controlled Trial of the Safety, Immunogenicity and Efficacy of a Candidate Malaria Vaccine, R21 Adjuvanted With Matrix-M (R21/MM), in 5-17 Month Old Children in Nanoro, Burkina Faso
Actual Study Start Date : May 7, 2019
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: Group 1
n=150. Age 5-17 month-old. 5mcg R21/25mcg Matrix-M.
Biological: R21 adjuvanted with 25mcg Matrix-M
Vaccine

Experimental: Group 2
n=150. Age 5-17 month-old. 5mcg R21/50mcg Matrix-M.
Biological: R21 adjuvanted with 50mcg Matrix-M
vaccine

Placebo Comparator: Group 3 (control group)
n=150. Age 5-17 month-old. Rabies Vaccine by the end of the trial.
Biological: Rabies Vaccine
Vaccine




Primary Outcome Measures :
  1. The protective efficacy (number of cases) against clinical malaria of R21 adjuvanted with Matrix-M in 5-17 month old children living in a malaria-endemic area [ Time Frame: for 6 months after the last vaccination ]

    We will look for the presence of axillary temperature ≥37.5°C AND P. falciparum parasites density > 5000 asexual forms/µL as a primary case definition of clinical malaria.

    - We will look for the presence of axillary temperature ≥37.5°C and/ or history of fever within the last 24 hours AND P. falciparum parasites density > 0 for a secondary case definition of clinical malaria.



Secondary Outcome Measures :
  1. Duration of Protective efficacy (number of cases) against clinical malaria [ Time Frame: for 12 months after administration of the final dose of vaccine. ]
    To assess the protective efficacy (number of cases) against clinical malaria of R21 adjuvanted with Matrix-M in 5-17 months old children living in a malaria-endemic area

  2. Efficacy (number of cases) against asymptomatic P. falciparum infection [ Time Frame: at 12 months after administration of the final dose of vaccine ]
    Primary case definition of asymptomatic P. falciparum infection: Presence of axillary temperature < 37.5°C and absence of history of fever within the last 24 hours; AND P. falciparum parasites density > 0 asexual forms/µLOcurrence of

  3. The safety and reactogenicity (number of adverse events) of R21 adjuvanted with Matrix-M in 5-17 month olds living in a malaria-endemic area in the month following each vaccination and at 12 months after administration of the final dose of vaccine [ Time Frame: for 12 months after administration of the final dose of vaccine. ]
    • Occurrence of solicited local and/or systemic reactogenicity signs and symptoms for 7 days following the vaccination
    • Occurrence of unsolicited adverse events for 28 days following the vaccination
    • Occurrence of serious adverse events for the duration of the trial

  4. The humoral immunogenicity (antibody response) of R21 adjuvanted with Matrix-M in 5-17 months old children living in a malaria-endemic area [ Time Frame: for 12 months after administration of the final dose of vaccine. ]
    • Comparison of immunogenicity (antibody responses to CSP) in the R21/MM vaccination group with those in the rabies vaccine group and the durability of responses
    • ELISA to quantify antibodies to the vaccine components (regions of the CS antigen including the NANP repeat region and other elements of the protein as well as anti HBs).


Other Outcome Measures:
  1. Exploratory Objectives: Efficacy (number of cases) against incident cases of severe malaria [ Time Frame: 6 months after administration of the final dose of vaccine ]

    Primary case definition of severe malaria:

    Presence of P. falciparum parasites density > 5000 asexuals forms/µL; AND one of more of the following criteria of disease severity:

    • Prostration
    • Respiratory distress
    • Blantyre coma score ≤ 3
    • Seizures: 2 or more
    • Hypoglycemia < 2.2 mmol/L
    • Acidosis BE ≤-8.0 mmol/L
    • Lactate ≥ 5.0 mmol/L
    • Anemia < 5.0 g/dL
    • Acute kidney injury
    • Pulmonary oedema
    • Significant bleeding
    • Shock (systolic BP <70mm Hg); AND

      -Without any of the following criteria of co- morbidity

    • Pneumonia (confirmed by X-ray)
    • Meningitis (confirmed by CSF examination)
    • Sepsis (with Positive blood culture)
    • Gastroenteritis with dehydration

  2. Exploratory Objectives: Gut microbiome (bacterial communities identified) effect on vaccine response. [ Time Frame: for 12 months after administration of the final dose of vaccine ]
    • DNA extraction and sequencing to determine differences in gut microbiome between those who respond to vaccination and those who don't.

  3. Exploratory Objectives: Genetic testing to elicit differences in vaccine response. [ Time Frame: for 12 months after administration of the final dose of vaccine ]
    • Genetic tests-determination of human HLA-type and genotyping of any other genes to assess impact on response to vaccination, including genome-wide SNP and sequence analysis.
    • Genetic testing of the DNA of malaria parasites identified during the study to determine if the vaccine preferentially protects against specific genetic types of P. falciparum.



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Ages Eligible for Study:   5 Months to 17 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy child aged 5-17 months at the time of first study vaccination
  • Provide written Informed consent of parent/guardian
  • Child and parent/guardian resident in the study area villages and anticipated to be available for vaccination and follow-up for 2 years following last dose of vaccination

Exclusion Criteria:

  • Clinically significant skin disorder (psoriasis, contact dermatitis etc.), immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, neurological illness.
  • Weight-for-age Z score of less than -3 or other clinical signs of malnutrition.
  • History of allergic reaction, significant IgE-mediated event, or anaphylaxis to immunisation.
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, e.g. egg products, neomycin.
  • Sickle cell disease.
  • Clinically significant laboratory abnormality as judged by the study clinician.
  • Blood transfusion within one month of enrolment.
  • Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
  • Previous vaccination with experimental malaria vaccines.
  • Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period.
  • Current participation in another clinical trial, or within 12 weeks of this study.
  • Known maternal HIV infection (No testing will be done by the study team).
  • 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 (For corticosteroids, this will mean prednisone, or equivalent, >= 0.5 mg/kg/day. Inhaled and topical steroids are allowed).
  • Any 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): NCT03896724


Contacts
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Contact: Rachel Roberts +44 (0)1865 611418 vaccinetrials@ndm.ox.ac.uk

Locations
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Burkina Faso
Institut de Recherche en Sciences de la Sante - Clinical Research Unit of Nanoro (IRSS-URCN) Recruiting
Nanoro, Burkina Faso
Contact: Halidou Tinto, Dr         
Sponsors and Collaborators
University of Oxford
European Commission

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Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT03896724     History of Changes
Other Study ID Numbers: VAC076
First Posted: April 1, 2019    Key Record Dates
Last Update Posted: July 2, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs