Safety and Immunogenicity of ChAd63 RH5 and MVA RH5 in Adults, Young Children and Infants Living in Tanzania

NCT ID: NCT03435874

Last Updated: 2019-09-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

63 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-12

Study Completion Date

2019-07-11

Brief Summary

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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.

Detailed Description

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* 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.

Conditions

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Malaria,Falciparum

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

A Phase Ib age de-escalation dose-escalation randomised, double-blind, controlled study of the safety and immunogenicity of heterologous prime-boost with the candidate malaria vaccines ChAd63 RH5 and MVA RH5
Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Double-blind.

Study Groups

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Group 1 Active

n=6. Age 18-35 years. 5x10 10 vp ChAd63 RH5 at D0 and 2x10 8 pfu MVA RH5 at D56.

Group Type EXPERIMENTAL

ChAd63 RH5

Intervention Type BIOLOGICAL

Vaccine

MVA RH5

Intervention Type BIOLOGICAL

Vaccine

Group 1 Comparator

n=3. Age 18-35 years. Rabies vaccine at D0 and D56.

Group Type PLACEBO_COMPARATOR

Rabies Vaccine

Intervention Type BIOLOGICAL

Vaccine

Group 2a Active

n=6. Age 1-6 years. 1x10 10 vp ChAd63 RH5 at D0 and 1x10 8 pfu MVA RH5 D56.

Group Type EXPERIMENTAL

ChAd63 RH5

Intervention Type BIOLOGICAL

Vaccine

MVA RH5

Intervention Type BIOLOGICAL

Vaccine

Group 2a Comparator

n=3. Age 1-6 years. Rabies vaccine at D0 and D56.

Group Type PLACEBO_COMPARATOR

Rabies Vaccine

Intervention Type BIOLOGICAL

Vaccine

Group 2b Active

n=12. Age 1-6 years. 5x10 10 vp ChAd63 RH5 at D0 and 2x10 8 pfu MVA RH5 D56.

Group Type EXPERIMENTAL

ChAd63 RH5

Intervention Type BIOLOGICAL

Vaccine

MVA RH5

Intervention Type BIOLOGICAL

Vaccine

Group 2b Comparator

n=6. Age 1-6 years. Rabies vaccine at D0 and D56.

Group Type PLACEBO_COMPARATOR

Rabies Vaccine

Intervention Type BIOLOGICAL

Vaccine

Group 3a Active

n=6. Age 6-11 months. 1x10 10 vp ChAd63 RH5 at D0 and 1x10 8 pfu MVA RH5 D56.

Group Type EXPERIMENTAL

ChAd63 RH5

Intervention Type BIOLOGICAL

Vaccine

MVA RH5

Intervention Type BIOLOGICAL

Vaccine

Group 3a Comparator

n=3. Age 6-11 months. Rabies vaccine at D0 and D56.

Group Type PLACEBO_COMPARATOR

Rabies Vaccine

Intervention Type BIOLOGICAL

Vaccine

Group 3b Active

n=12. Age 6-11 months. 5x10 10 vp ChAd63 RH5 at D0 and 2x10 8 pfu MVA RH5 D56.

Group Type EXPERIMENTAL

ChAd63 RH5

Intervention Type BIOLOGICAL

Vaccine

MVA RH5

Intervention Type BIOLOGICAL

Vaccine

Group 3b Comparator

n=6. Age 6-11 months. Rabies vaccine at D0 and D56.

Group Type PLACEBO_COMPARATOR

Rabies Vaccine

Intervention Type BIOLOGICAL

Vaccine

Interventions

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ChAd63 RH5

Vaccine

Intervention Type BIOLOGICAL

MVA RH5

Vaccine

Intervention Type BIOLOGICAL

Rabies Vaccine

Vaccine

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* 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.
Minimum Eligible Age

6 Months

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Ifakara Health Institute

OTHER

Sponsor Role collaborator

Medical Research Council

OTHER_GOV

Sponsor Role collaborator

University of Oxford

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Angela M Minassian

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Locations

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Ifakara Health Institute Clinical Trial Facility

Bagamoyo, , Tanzania

Site Status

Countries

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Tanzania

Other Identifiers

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VAC070

Identifier Type: -

Identifier Source: org_study_id

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