- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03435874
Safety and Immunogenicity of ChAd63 RH5 and MVA RH5 in Adults, Young Children and Infants Living in Tanzania
September 3, 2019 updated by: University of Oxford
A Phase Ib Age De-escalation Dose-escalation Randomised, Double-blind, Controlled Study of the Safety and Immunogenicity of ChAd63 RH5 and MVA RH5 Given Intramuscularly at 0 and 2-months in Healthy Adults, Children and Infants in Tanzania
This is a dose-escalation, age de-escalation randomised double-blind controlled Phase Ib trial to assess the safety, tolerability and immunogenicity of ChAd63-RH5 administered with MVA-RH5 in a heterologous prime-boost regimen.
Adults (18-35 years), young children (1-6 years) and infants (6-11 months) will be enrolled in the study.
Safety data will be collected for each of the vaccination regimens.
The humoral and cellular immune responses generated by each of these regimens will be assessed.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
- Experimental design: Phase Ib, double blind, age de-escalation dose-escalation, randomized (2:1 ratio), controlled trial.
- Healthy adults (18-35 years), young children (1-6 years) and infants (6-11 months) will be screened; those determined to be eligible, based on the inclusion and exclusion criteria, will be enrolled in the study.
- Route of administration of ChAd63-RH5 (day 0) and MVA-RH5 (2 months): both vaccines will be administered by the intramuscular route to the left deltoid.
- Each participant will be observed for at least 1 hour after vaccination to evaluate and treat any acute adverse events (AEs).
- There will be 7-day follow-up period for solicited AEs post-vaccination: Day 0, 2 and 7 evaluations will be carried out by the study clinician at the study centre and day 1, 3, 4, 5 and 6 evaluations will be carried out by a trained community health worker in the participant's home, after each vaccination.
- There will be a 28-day (day of vaccination and 28 subsequent days) follow-up after each vaccine dose for reporting unsolicited symptoms.
- Serious adverse events (SAEs) will be recorded throughout the study period. Prior to vaccination, any SAEs due directly to study procedures will be captured. All SAEs will be captured beginning with the administration of the priming dose of ChAd63 RH5 and ending 4 months after the booster dose with MVA RH5.
- Antibodies to RH5_FL will be determined at baseline and 14, 28, 56, 63, 84, 112, 140 and 168 days after ChAd63 RH5 in all participants.
- Cellular immune responses to RH5 will be evaluated at baseline and 14 (adults only), 28, 56, 63, 84 and 168 days after ChAd63 RH5 in all participants.
- The duration of involvement in the study from enrolment will be approximately 6 months. The vaccination phase of the study takes 9 weeks and the post-vaccination follow-up lasts for 4 months after the last dose.
Study Type
Interventional
Enrollment (Actual)
63
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Bagamoyo, Tanzania
- Ifakara Health Institute Clinical Trial Facility
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
6 months to 35 years (Child, Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
Only participants who meet all the inclusion criteria will be enrolled into the trial;
- Group 1: Healthy male or female adults aged 18-35 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 provide consent of their willingness to take Depo-Provera contraceptive during the study and safety follow-up period.
- Groups 2a & 2b: Healthy male or female young children aged 1-6 years at the time of enrolment with signed consent obtained from parents or guardians.
- Groups 3a & 3b: 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 9 months from the date of recruitment) or permanent residence in Bagamoyo town.
- Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2; or young children and infants with Z-score of weight-for-age within ±2SD.
Exclusion Criteria:
The participant may not enter the trial if ANY of the following apply:
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group 1 Active
n=6.
Age 18-35 years.
5x10 10 vp ChAd63 RH5 at D0 and 2x10 8 pfu MVA RH5 at D56.
|
Vaccine
Vaccine
|
Placebo Comparator: Group 1 Comparator
n=3.
Age 18-35 years.
Rabies vaccine at D0 and D56.
|
Vaccine
|
Experimental: Group 2a Active
n=6.
Age 1-6 years.
1x10 10 vp ChAd63 RH5 at D0 and 1x10 8 pfu MVA RH5 D56.
|
Vaccine
Vaccine
|
Placebo Comparator: Group 2a Comparator
n=3.
Age 1-6 years.
Rabies vaccine at D0 and D56.
|
Vaccine
|
Experimental: Group 2b Active
n=12.
Age 1-6 years.
5x10 10 vp ChAd63 RH5 at D0 and 2x10 8 pfu MVA RH5 D56.
|
Vaccine
Vaccine
|
Placebo Comparator: Group 2b Comparator
n=6.
Age 1-6 years.
Rabies vaccine at D0 and D56.
|
Vaccine
|
Experimental: Group 3a Active
n=6.
Age 6-11 months.
1x10 10 vp ChAd63 RH5 at D0 and 1x10 8 pfu MVA RH5 D56.
|
Vaccine
Vaccine
|
Placebo Comparator: Group 3a Comparator
n=3.
Age 6-11 months.
Rabies vaccine at D0 and D56.
|
Vaccine
|
Experimental: Group 3b Active
n=12.
Age 6-11 months.
5x10 10 vp ChAd63 RH5 at D0 and 2x10 8 pfu MVA RH5 D56.
|
Vaccine
Vaccine
|
Placebo Comparator: Group 3b Comparator
n=6.
Age 6-11 months.
Rabies vaccine at D0 and D56.
|
Vaccine
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Solicited symptoms after vaccination.
Time Frame: 7-day surveillance after each vaccination
|
Frequency and severity (according to internationally recognised grading tables) of local and systemic solicited adverse events will be recorded for 7 days after each vaccination.
For each, a causal relationship between the adverse event and IMP will be assigned.
|
7-day surveillance after each vaccination
|
Unsolicited symptoms after each vaccination.
Time Frame: 28-day surveillance after each vaccination.
|
Frequency and severity (according to internationally recognised grading tables) of unsolicited adverse events will be recorded for 28 days after each vaccination.
For each, a causal relationship between the adverse event and IMP will be assigned.
|
28-day surveillance after each vaccination.
|
Serious adverse events during the study period.
Time Frame: Surveillance from first dose of vaccine to end of study (approximately 6 months from first vaccination).
|
All serious adverse events from the first dose of IMP until the end of the study (approximately 6 months from first vaccination) will be recorded, causality assigned and reported to the Chief Investigator (as the Sponsor's representative) within 24 hours of the Investigator being aware of the suspected SAE.
The Safety Monitoring Committee will be notified immediately by the PI if SAEs are deemed possibly, probably or definitely related to study interventions.
|
Surveillance from first dose of vaccine to end of study (approximately 6 months from first vaccination).
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Anti-RH5 antibody concentration by ELISA.
Time Frame: At baseline, and days 14 (adults only), 28, 56, 70, 84, 112, 140 and 168 after the first vaccination.
|
Evaluation of the magnitude of antibody responses to PfRH5 in adults, children and infants residing in a malaria endemic country, as measured by ELISA
|
At baseline, and days 14 (adults only), 28, 56, 70, 84, 112, 140 and 168 after the first vaccination.
|
Growth inhibition activity of sera from vaccinees on a panel of P. falciparum parasites.
Time Frame: At baseline, and days 14 (adults only), 28, 56, 70, 84, 112, 140 and 168 after the first vaccination.
|
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
|
At baseline, and days 14 (adults only), 28, 56, 70, 84, 112, 140 and 168 after the first vaccination.
|
Avidity of anti-RH5 antibodies by ELISA and surface plasmon resonance (SPR) and/or other assays (to be defined).
Time Frame: At baseline, and days 14 (adults only), 28, 56, 70, 84, 112, 140 and 168 after the first vaccination.
|
Evaluation of the longevity of antibody responses to PfRH5 in adults, children and infants residing in a malaria endemic country, as measured by ELISA, SPR +/- other assays
|
At baseline, and days 14 (adults only), 28, 56, 70, 84, 112, 140 and 168 after the first vaccination.
|
Cellular immune responses to the RH5 by ELISpot assay and/or Intracellular Cytokine Staining (ICS) and/or other assays to be defined.
Time Frame: At baseline, and days 14 (adults only), 28, 56, 70, 84, 112, 140 and 168 after the first vaccination.
|
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 Intracellular Cytokine Staining (ICS) and/or other assays to be defined.
|
At baseline, and days 14 (adults only), 28, 56, 70, 84, 112, 140 and 168 after the first vaccination.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Angela M Minassian, University of Oxford
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 12, 2018
Primary Completion (Actual)
July 11, 2019
Study Completion (Actual)
July 11, 2019
Study Registration Dates
First Submitted
January 8, 2018
First Submitted That Met QC Criteria
February 9, 2018
First Posted (Actual)
February 19, 2018
Study Record Updates
Last Update Posted (Actual)
September 4, 2019
Last Update Submitted That Met QC Criteria
September 3, 2019
Last Verified
January 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- VAC070
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Malaria,Falciparum
-
University of OxfordTerminatedP. Falciparum MalariaThailand
-
National Institute of Allergy and Infectious Diseases...CompletedAccute Falciparum MalariaMali
-
Medical University of ViennaInternational Centre for Diarrhoeal Disease Research, Bangladesh; Armed Forces...CompletedAzithromycin Combination Therapy for the Treatment of Uncomplicated Falciparum Malaria in BangladeshUncomplicated Falciparum MalariaBangladesh
-
Medecins Sans Frontieres, NetherlandsUniversity of Oxford; Mahidol University; Disease Control, Department of Health...UnknownUncomplicated Falciparum MalariaMyanmar
-
University of OxfordNanyang Technological University; Texas Biomedical Research InstituteCompletedP. Falciparum Malaria | P. Falciparum Malaria Mixed InfectionThailand
-
University of OxfordWellcome Trust; Ministry of public Health AfghanistanCompletedVivax Malaria | Uncomplicated Falciparum MalariaAfghanistan
-
Novartis PharmaceuticalsRecruitingUncomplicated Plasmodium Falciparum MalariaCôte D'Ivoire, Kenya, Ghana, Uganda
-
Medicines for Malaria VentureCompletedUncomplicated Plasmodium Falciparum MalariaUganda, Benin, Burkina Faso, Congo, The Democratic Republic of the, Gabon, Mozambique, Vietnam
-
University of OxfordMahidol Oxford Tropical Medicine Research Unit; Department of Medical Research...WithdrawnUncomplicated Falciparum Malaria | Artemisinin-resistant
-
Novartis PharmaceuticalsCompletedAcute Uncomplicated P. Falciparum Malaria
Clinical Trials on Rabies Vaccine
-
CureVacCompleted
-
Sanofi Pasteur, a Sanofi CompanyActive, not recruiting
-
Sanofi Pasteur, a Sanofi CompanyCompleted
-
Sanofi Pasteur, a Sanofi CompanyCompleted
-
Sanofi Pasteur, a Sanofi CompanyCompleted
-
Yisheng Biopharma (Singapore) Pte. Ltd.Duke-NUS Graduate Medical SchoolCompleted
-
NovartisNovartis VaccinesCompletedJapanese Encephalitis | Rabies | Pre-Exposure ProphylaxisThailand
-
Queen Saovabha Memorial InstituteUnknown
-
Leiden University Medical CenterUnknownRabies Pre-exposure ProphylaxisNetherlands
-
Queen Saovabha Memorial InstituteChulalongkorn UniversityRecruiting