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 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202205485639426 Date of Registration: 27/05/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A Phase Ib multi-stage Plasmodium falciparum malaria vaccine study to assess the safety and immunogenicity of the blood-stage vaccine candidate RH5.2 virus-like particle (VLP) in Matrix-MTM and the pre-erythrocytic stage vaccine candidate R21 in Matrix-MTM, both alone and in combination, in adults and infants in the Gambia - (VAC086)
Official scientific title A Phase Ib multi-stage Plasmodium falciparum malaria vaccine study to assess the safety and immunogenicity of the blood-stage vaccine candidate RH5.2 virus-like particle (VLP) in Matrix-MTM and the pre-erythrocytic stage vaccine candidate R21 in Matrix-MTM, both alone and in combination, in adults and infants in the Gambia
Brief summary describing the background and objectives of the trial The VAC086 is a phase Ib age de-escalation dose escalation trial, aiming at assessing the safety and immunogenicity of the blood-stage vaccine candidate RH5.2 virus-like particle (VLP) and the pre-erythrocytic stage vaccine candidate R21, both alone and in combination, in adults and infants in the Gambia. This trial will conduct a staggered recruitment of 96 healthy volunteers among which 30 adults aged 18-45 years and 66 infants aged 5-17months. Each participant will receive 3 doses of either RH5.2-VLP, R21 or a combination of both at M0, M1, M2 or M6 and will be follow-up for 24-30 months.
Type of trial CCT
Acronym (If the trial has an acronym then please provide) VAC086
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 01/09/2022
Actual trial start date
Anticipated date of last follow up 31/03/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 96
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
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 Non-randomised Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group RH5 2 VLP Rh5.2 VLP in adults: first group = 10ug (per injection) and second group=50ug/dose in infants Rh5.2 (5ug/dose) . Single vaccine shot received at three time points month 1, month 2 and month 3 or month 6. RH5.2-VLP – a recombinant protein virus-like particle vaccine against the RH5 antigen 42
Experimental Group R21 in infants R21 (5ug/dose) Single vaccine shot received at three time points month 1, month 2 and month 3 or month 6. R21 – a protein particle comprising recombinant HBsAg fused to the central repeat and the C-terminus of the circumsporozoite protein (CSP) 22
Experimental Group R21 and RH5 2 adults: Rh5.2 (10ug/dose) +R21 (10ug)/per dose; infants: Rh5.2 (5ug/dose) +R21 (5ug/dose). Single vaccine shot received at three time points month 1, month 2 and month 3 or month 6. Combination of R21 and Rh5.2 which were already described 32
Control Group No control group Not applicable Not applcable Not applicable 0 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Only participants who meet all the inclusion criteria will be enrolled into the trial; • Groups 1, 2 and 6-9: Healthy male or female infants aged 5-17 months at the time of enrolment with signed consent obtained from parents or guardians. • Groups 3-5: Healthy male or female adults aged 18-45 years at the time of enrolment with signed consent. • Groups 3-5 (Female participants only): Must be non-pregnant (as demonstrated by a negative urine pregnancy test), and practice continuous effective contraception for the 24 to 30 month duration of the study (see section 9.9). • Planned long-term (at least 24 months from the date of recruitment) or permanent residence in the study area. • Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2; or infants with Z-score of weight-for-age within ±2SD. 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). • History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, e.g., Kathon, neomycin, betapropiolactone. • Any history of anaphylaxis in relation to vaccination. • Clinically significant laboratory abnormality at grade 2 or above as judged by the PI or other delegated individual. • Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate. • Receipt of any vaccine in the 30 days preceding enrolment, or planned receipt of any other vaccine within 30 days following each study vaccination. This excludes COVID-19 vaccines, which should not be received between 14 days before to 7 days after any study vaccination, and EPI vaccines (for infants), which should not be received between 14 days before to 28 days after any study vaccination. • History of vaccination with previous malaria vaccines. Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment in adults or at any time for infants, or planned use during the study period. • Suspected or known current alcohol abuse. Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment in adults or at any time for infants, or planned use during the study period. • Suspected or known current alcohol abuse. • Suspected or known injecting drug abuse in the 5 years preceding enrolment. • Seropositive for hepatitis B surface antigen (HBsAg), hepatitis C (HCV IgG) or HIV. For infants, any history of vertical exposure to HIV infection. • 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. • Positive malaria by PCR 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. Adolescent: 13 Year(s)-17 Year(s),Adult: 18 Year(s)-44 Year(s),Child: 6 Year-12 Year,Infant: 1 Month(s)-12 Month(s),Infant: 13 Month(s)-24 Month(s),Preschool Child: 2 Year-5 Year 5 Month(s) 45 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 22/03/2022 Scientific Coordinating Commitee
Ethics Committee Address
Street address City Postal code Country
Atlantic Road, Fajara, Banjul, PO Box 27 Gambia
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. The following parameters will be assessed: • Occurrence of solicited local reactogenicity signs and symptoms for 7 days following each vaccination • Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following each vaccination • Occurrence of unsolicited adverse events for 28 days following the vaccination • Change from baseline for safety laboratory measures for 28 days following vaccination • Occurrence of serious adverse events during the whole study duration Solicited AE data will be collected daily for the first seven days following first vaccination and three days following each subsequent vaccination via clinic and home visits. Unsolicited AE data will be collected at each visit via clinical review, clinical examination (including observations) and laboratory results. This AE data will be tabulated, detailing frequency, duration and severity of AEs. Haematological and biochemical laboratory values will be presented according to local grading scales. Serious adverse events (SAEs), adverse events (AEs) of special interest and withdrawal due to AE(s)/SAE(s) will be described in detail. Volunteers will be followed for approximately 24-30 months following initial trial vaccination and approximately 22-24 months following the third dose. Volunteers will be followed for approximately 24-30 months following initial trial vaccination and approximately 22-24 months following the third dose.
Secondary Outcome Priority immunology: • RH5 serology (participants vaccinated with RH5.2-VLP only) • R21 serology (participants vaccinated with R21 only) • Hepatitis B serology • Growth Inhibition Activity (GIA) (participants vaccinated with RH5.2-VLP only) • Serum total IgG concentration determination • Inhibition of sporozoite invasion assay (ISI) (participants vaccinated with R21 only) Possibilities for exploratory immunology (to be confirmed): • P. falciparum anti-schizont ELISA • Flow cytometry (B cell/TfH/ICS) (adults only) • Peptide arrays • mAb isolation (adults only) The above will be detailed further in the Immunology Analysis Plan. Blood samples will be taken at the timepoints shown in table 4. Samples are required from a number of key timepoints including baseline and post vaccination of V+7 (adults only), V+14, V+28 to allow for antibody kinetics and magnitude assessment, and late timepoints to assess longevity of response. For the priority immunology, ELISA will be performed at every timepoint where ‘immunology serum’ is shown in table 4. GIA will be performed at peak of response after the third vaccination, based on previous work this is likely to be at V3+14 or V3+28. A minimum of 2mL serum is required to perform GIA on individuals to assess functionality of antibodies, so the bleeds at V3+14 (i.e. day 70/196) therefore need to be at least 4mL due to ~50% being serum. Taking less than 4mL of serum at these key time-points would compromise our ability to meet our key immunology endpoints and therefore we require serum collection at V+28 in case V+14 sample is compromised to ensure antibody functionality in GIA can be assessed. Day 70/196
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Medical Research Council Unit The Gambia at the LSHTM Atlantic Road, Fajara, Banjul PO Box 27 Gambia
FUNDING SOURCES
Name of source Street address City Postal code Country
European and Developing Countries Clinical Trials Partnership Tygerberg 7505 Cape Town 19070 South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Oxford University Offices, Wellington Square, Oxford London OX1 2JD United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries Angela M Minassian angela.minassian@ndm.ox.ac.uk +441865611425 Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford, Churchill Hospital, Old Road, Headington, Oxford,
City Postal code Country Position/Affiliation
London OX3 7LE United Kingdom Chief Investigator
Role Name Email Phone Street address
Principal Investigator Umberto Dalessandro udalessandro@mrc.gm +2203320049 Medical Research Council Unit The Gambia at LSHTM Atlantic Boulevard, Fajara
City Postal code Country Position/Affiliation
Banjul 273 Gambia Principal Investigator
Role Name Email Phone Street address
Scientific Enquiries Annette Erhart Annette.Erhart@lshtm.ac.uk +2207009779 Medical Research Council Unit The Gambia at LSHTM Atlantic Boulevard, Fajara
City Postal code Country Position/Affiliation
Banjul 273 Gambia Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Anonymised trial data will be made publicly available to the scientific community through a data repository. An appropriate data repository will be selected by the sponsor after discussion with research data experts and in accordance with trial agreements and data sharing regulations Study Protocol Will be communicated later Will be communicated Later
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information