Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT03896724
Recruitment Status : Recruiting
First Posted : April 1, 2019
Last Update Posted : March 23, 2020
Sponsor:
Collaborators:
Institut de Recherche en Sciences de la Sante - Clinical Research Unit of Nanoro (IRSS-URCN)
European and Developing Countries Clinical Trials Partnership (EDCTP)
Information provided by (Responsible Party):
University of Oxford

Tracking Information
First Submitted Date  ICMJE January 18, 2019
First Posted Date  ICMJE April 1, 2019
Last Update Posted Date March 23, 2020
Actual Study Start Date  ICMJE May 7, 2019
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2019)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2020)
  • Duration of Protective efficacy (number of cases) against clinical malaria [ Time Frame: for 12 months after administration of the third dose of vaccine, and for 6 and 12 months after a booster vaccination ]
    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
  • Efficacy (number of cases) against asymptomatic P. falciparum infection [ Time Frame: at 12 months after administration of the third dose of vaccine, and for 12 months after a booster vaccination ]
    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
  • 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 third dose of vaccine, and for 12 months after a booster vaccination ]
    • 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
  • 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 third dose of vaccine, and for 6 months after a booster vaccination ]
    • 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2019)
  • 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
  • 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
  • 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
  • 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).
Current Other Pre-specified Outcome Measures
 (submitted: March 27, 2019)
  • 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
  • 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.
  • 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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Safety, Immunogenicity and Efficacy of R21 Matrix-M in 5-17 Month Old Children in Nanoro, Burkina Faso
Official Title  ICMJE 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
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.
Detailed Description

Participants will be randomised 2:1 to receive vaccination with the IMP (R21 adjuvanted with Matrix-M; Group 1 and Group 2) or control vaccination with Rabies Vaccine (Group 3). 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 25μg Matrix-M, 4 weeks apart via the intramuscular route, and a booster vaccination one year following the third vaccination.

Group 2 (active vaccine group) participants will receive 3 vaccinations of R21 5μg with 50μg Matrix-M, 4 weeks apart via the intramuscular route, and a booster vaccination one year following the third vaccination.

Group 3 (control group) participants will receive three vaccinations with rabies vaccine, four weeks apart, all given intramuscularly and a fourth vaccination with rabies vaccine one year following the third vaccination.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Malaria,Falciparum
Intervention  ICMJE
  • Biological: R21 adjuvanted with 25mcg Matrix-M
    Vaccine
  • Biological: Rabies Vaccine
    Vaccine
  • Biological: R21 adjuvanted with 50mcg Matrix-M
    vaccine
Study Arms  ICMJE
  • Experimental: Group 1
    n=150. Age 5-17 month-old. 5mcg R21/25mcg Matrix-M.
    Intervention: Biological: R21 adjuvanted with 25mcg Matrix-M
  • Experimental: Group 2
    n=150. Age 5-17 month-old. 5mcg R21/50mcg Matrix-M.
    Intervention: Biological: R21 adjuvanted with 50mcg Matrix-M
  • Placebo Comparator: Group 3 (control group)
    n=150. Age 5-17 month-old. Rabies Vaccine by the end of the trial.
    Intervention: Biological: Rabies Vaccine
Publications * Datoo MS, Natama MH, Somé A, Traoré O, Rouamba T, Bellamy D, Yameogo P, Valia D, Tegneri M, Ouedraogo F, Soma R, Sawadogo S, Sorgho F, Derra K, Rouamba E, Orindi B, Ramos Lopez F, Flaxman A, Cappuccini F, Kailath R, Elias S, Mukhopadhyay E, Noe A, Cairns M, Lawrie A, Roberts R, Valéa I, Sorgho H, Williams N, Glenn G, Fries L, Reimer J, Ewer KJ, Shaligram U, Hill AVS, Tinto H. Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial. Lancet. 2021 May 15;397(10287):1809-1818. doi: 10.1016/S0140-6736(21)00943-0. Epub 2021 May 5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 27, 2019)
450
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2021
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Months to 17 Months   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Rachel Roberts +44 (0)1865 611418 vaccinetrials@ndm.ox.ac.uk
Listed Location Countries  ICMJE Burkina Faso
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03896724
Other Study ID Numbers  ICMJE VAC076
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Oxford
Study Sponsor  ICMJE University of Oxford
Collaborators  ICMJE
  • Institut de Recherche en Sciences de la Sante - Clinical Research Unit of Nanoro (IRSS-URCN)
  • European and Developing Countries Clinical Trials Partnership (EDCTP)
Investigators  ICMJE Not Provided
PRS Account University of Oxford
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP