Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201710002722229 Date of Approval: 26/10/2017
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A study to assess new malaria vaccines ChAd63 RH5 and MVA RH5 in Tanzanian adults, children and infants
Official scientific title 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 administered intramuscularly according to a 0, 2-month vaccination schedule in healthy adults, young children and infants in Tanzania.
Brief summary describing the background and objectives of the trial Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is a new generation and highly promising blood stage malaria vaccine antigen. Preclinical and early clinical data show the antigen elicits functional antibodies against merozoites in non-human primates and malaria-naïve UK adults in contrast to those elicited by natural malaria exposure. The safety and capability of PfRH5 immunisation to induce functional immune responses in adults, young children and infants residing in malaria endemic countries is unknown. Using an age de-escalation dose-escalation randomised double-blind controlled trial, and established immunological techniques, the ARL candidate will establish the safe and well-tolerated dose of PfRH5 in adults, young children and infants and characterise the magnitude, quality and longevity of immune responses following immunization by a heterologous prime-boost approach with chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) expressing PfRH5. The study will recruit volunteers from low malaria transmission areas in Bagamoyo, Tanzania. The study will provide new knowledge with regard to the potential for PfRH5 as a malaria vaccine and inform decisions to conduct larger field trials to evaluate efficacy. The immunological outcomes will provide data on the human antibody response, to determine if there is scope to further improve the PfRH5 immunogen in future iterations of the vaccine
Type of trial RCT
Acronym (If the trial has an acronym then please provide) VAC070
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Prevention
Anticipated trial start date 08/01/2018
Actual trial start date
Anticipated date of last follow up 27/09/2018
Actual Last follow-up date
Anticipated target sample size (number of participants) 63
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
29-17 OXTREC
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using randomisation table created by a computer software program. Allocation determined by independent statistician. Masking/blinding used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using randomisation table created by a computer software program. Allocation determined by independent statistician. Masking/blinding used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using randomisation table created by a computer software program. Allocation determined by independent statistician. Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Group 1 5 x 10^10 vp ChAd63 RH5 and boost with 2 x 10^8 pfu MVA RH5 8 weeks later 8 weeks ChAd63 RH5 and MVA RH5 6
Experimental Group Group 2a 1 x 10^10 vp ChAd63 RH5 and boost with 1 x 10^8 pfu MVA RH5 8 weeks later 8 weeks ChAd63 RH5 and MVA RH5 6
Experimental Group Group 2b 5 x 10^10 vp ChAd63 RH5 and boost with 2 x 10^8 pfu MVA RH5 8 weeks later 8 weeks ChAd63 RH5 and MVA RH5 12
Experimental Group Group 3a 1 x 10^10 vp ChAd63 RH5 and boost with 1 x 10^8 pfu MVA RH5 8 weeks later 8 weeks ChAd63 RH5 and MVA RH5 6
Experimental Group Group 3b 5 x 10^10 vp ChAd63 RH5 and boost with 2 x 10^8 pfu MVA RH5 8 weeks later 8 weeks ChAd63 RH5 and MVA RH5 12
Control Group Group 1 1ml twice, 8 weeks apart 8 weeks Rabies 3 Placebo
Control Group Group 2a 1ml twice, 8 weeks apart 8 weeks Rabies 3 Placebo
Control Group Group 2b 1ml twice, 8 weeks apart 8 weeks Rabies 6 Placebo
Control Group Group 3a 1ml twice, 8 weeks apart 8 weeks Rabies 3 Placebo
Control Group Group 3b 1ml twice, 8 weeks apart 8 weeks Rabies 6 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
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. 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. 6 Month(s) 35 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 24/10/2017 Ifakara Health Institute IRB
Ethics Committee Address
Street address City Postal code Country
Kiko Steet Dar es salaam P.O. Box 78373 Tanzania
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 30/10/2017 National Health Research Ethics Sub-Committee
Ethics Committee Address
Street address City Postal code Country
Ocean road Dar es salaam P.O. Box 9653 Tanzania
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 30/10/2017 Oxford Tropical Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Wellington Square Oxford OX1 2JD United Kingdom
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Adverse events (AE) 1. 7-day surveillance after each vaccination for solicited AEs. 2. 28-day surveillance after each vaccination for unsolicited AEs 3. Surveillance from first dose to end of study for SAEs.
Secondary Outcome Antti-RH5 antibody concentration by ELIS At baseline, and days 14 (adults only), 28, 56, 70, 84, 112, 140 and 168 after the first vaccination.
Secondary Outcome Growth inhibition activity of sera from vaccinees on a panel of Pf parasites. At baseline, and days 14 (adults only), 28, 56, 70, 84, 112, 140 and 168 after the first vaccination
Secondary Outcome Avidity of anti-RH5 antibodies by ELISA and SPR 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.
Secondary Outcome Cellular immune responses to the RH5 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
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
BRTC Clinical trial facility Kingani Bagamoyo Box 74 Tanzania
FUNDING SOURCES
Name of source Street address City Postal code Country
MRC UK 14th floor One Kemble Street London WC2B 4AN United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Oxford Wellington Square Oxford OX1 2JD United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Simon Draper Old Road Campus Research Building Roosevelt Drive Headington Oxford OX3 7DQ United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Ally Olotu aolotu@ihi.or.tz +255 718 927 104 Kingani
City Postal code Country Position/Affiliation
Bagamoyo Box 74 Tanzania Chief Research Officer
Role Name Email Phone Street address
Public Enquiries Saumu Ahmed sahmed@ihi.or.tz +255 784 358 670 Kingani
City Postal code Country Position/Affiliation
Bagamoyo Box 74 Tanzania Project Manager
Role Name Email Phone Street address
Scientific Enquiries Simon Simon simon.draper@ndm.ox.ac.uk +44 (0)1865 617624 Old Road Campus Research Building Roosevelt Drive Headington
City Postal code Country Position/Affiliation
Oxford OX3 7DQ United Kingdom UK Senior Laboratory Investigator
REPORTING
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