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.: PACTR202312585218142 Date of Registration: 07/12/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title In-vivo Transmission model in semi-immune adults
Official scientific title Adaptation of blood-stage Controlled Human Malaria Infection for evaluation of transmission-blocking malaria interventions in malaria-endemic countries
Brief summary describing the background and objectives of the trial in vivo transmission blocking model for early-stage clinical evaluation of TBV is needed to rapidly down-select promising candidate vaccines before large field trials are conducted. Although such model has been studied in malaria naïve population, it is important to establish this model in target populations to provide relevant results that considers the genetic background and underlying natural immunity. Objectives of the study Primary objectives To determine the safety of P.falciparum blood-stage CHMI model adapted for transmission studies in semi-immune healthy adults residing in Bagamoyo,Tanzania. Secondary Objective To assess gametocyte infectiousness in Anopheles mosquitoes by mosquito feeding assay (Direct Membrane Feeding Assay (DMFA) / Direct Skin Feeding Assay (DFA) To determine the prevalence of gametocytaemia in semi-immune healthy adults following blood infection challenge and treatment with sub-curative doses of two different antimalarial regimens. To investigate the dynamics of gametocyte development, maturation and sex ratio by molecular markers of sexual stage development following blood infection challenge in semi-immune healthy adults residing in Bagamoyo, Tanzania. Exploratory objectives To determine the effect of naturally acquired antibody and cellular immune responses to blood-stage and gametocyte antigens on gametocyte development, dynamics and their infectivity following challenge with viable Plasmodium falciparum-infected human erythrocytes in healthy semi-immune adults residing in Bagamoyo, Tanzania. To assess the correlation of the ratio of gametocyte commitment transcription factor pfap2-g transcript levels to ring-stage asexual sbp1 transcripts as a proxy of sexually committed ring stage parasites
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Treatment: Drugs
Anticipated trial start date 09/01/2024
Actual trial start date
Anticipated date of last follow up 13/02/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 24
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
Blood CHMI Trans Ifakara Health Institute
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 a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Piperaquine Orally as a single dose of 480mg (320mg+160mg). single dose The first arm will receive Piperaquine tablets, that will be administered orally. Sub-curative regimen will be given as two tablets of 320mg and 160mg (total of 480mg). 12
Control Group Doxycycline (100mg tablets strength as Doxycycline hyclate) that will also be administered orally. Sub-curative regimen will be given as 1 tablet (100mg) once daily for 7 days. 7 days The second arm will receive Doxycycline (100mg tablets strength as Doxycycline hyclate) that will also be administered orally. Sub-curative regimen will be given as 1 tablet (100mg) once daily for 7 days. 12 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Male volunteers aged 18-45 years and in good health. Volunteer has adequate understanding of the procedures of the study and is able and willing (in the investigator's opinion) to comply with all study requirements. Participant is willing and able to give informed consent for participation in the trial. Participant with low malaria exposure as determined by anti-schizont ELISA Literacy in Kiswahili. Anti-schizont antibody levels below 50th centile of the most recently available population anti-schizont in Bagamoyo district Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, gastrointestinal, renal, hepatic, neurological, dermatological (e.g. psoriasis, contact dermatitis etc.), allergy, endocrine, malignant, haematological, infectious, immunodeficient, psychiatric and other disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results. A heightened risk of cardiovascular disease, as determined by: an estimated ten-year risk of fatal cardiovascular disease of ≥5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE); history, or evidence at screening, of clinically significant arrhythmia, prolonged QT-interval or other clinically relevant ECG abnormalities; or a positive family history of cardiac events in 1st or 2nd degree relatives <50 years old. Body mass index (BMI) of <18 or >30 Kg/m2 A medical history of functional asplenia Female volunteers Confirmed parasite positive by PCR a day before challenge i.e., at C-1. Screening tests positive for Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) Chronic use (>30 days) of i) immunosuppressive drugs, ii) antibiotics, iii) or other immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral antihistamines exempted) or expected use of such during the study period. Any recent (within 30 days) or current systemic therapy with an antibiotic or drug with potential antimalarial activity (chloroquine, doxycycline, tetracycline, piperaquine, benzodiazepine, flunarizine, fluoxetine, tetracycline, azithromycin, clindamycin, erythromycin, hydroxychloroquine, etc.) (Allowable time frame for use at the Investigator'sdiscretion). History of malignancy of any organ system (other than localized basal cell carcinoma of the Adult: 19 Year-44 Year 18 Year(s) 45 Year(s) Male
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 31/03/2023 National Institute for Medical Research
Ethics Committee Address
Street address City Postal code Country
3 Barack Obama Drvie Dar es salaam 9653 United Republic of Tanzania
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Frequency of solicited and unsolicited adverse events. Up to day 98 after blood infection challenge.
Secondary Outcome Magnitude of Adverse Events both solicitated and Unsolicited. Up to day 98 after blood infection challenge.
Secondary Outcome Rate of Mosquito infections (proportion of infected mosquitoes) 14, 21 and 28 days after infection challenge
Secondary Outcome Infection burden (Oocysts density in infected mosquitoes) 14, 21 and 28 days after infection challenge
Secondary Outcome Number of volunteers in each study arm that show prevalence of gametocytes as defined by quantitative reverse-transcriptase PCR (qRT-PCR) for CCp4 (female) and pfMGET (male) mRNA with a threshold of 5 gametocytes/mL for positivity. Up to day 28 after blood infection challenge
Secondary Outcome Time to peak density gametocytes from the time of challenge as measured by qRT-PCR. Up to day 28 after the blood infection challenge
Secondary Outcome The area under the curve of gametocyte density versus time for both arms of the study Up to day 28 after the blood infection challenge
Secondary Outcome Gametocyte commitment after the blood infection challenge as estimated by dividing the peak gametocyte by the peak of asexual parasites Up to day 28 after the blood infection challenge
Secondary Outcome Gametocyte Sex-ratio after blood infection challenge as measured by the proportion of male gametocytes versus female gametocytes. Up to day 28 after the blood infection challenge
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Bagmoyo Clinical Trial Facility kingani Pwani United Republic of Tanzania
FUNDING SOURCES
Name of source Street address City Postal code Country
European and Developing Countries Clinical Trials Partnership 2509 AA The Hague Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Ifakara Health Institute Bagamoyo Pwani 74 United Republic of Tanzania Research Institute
COLLABORATORS
Name Street address City Postal code Country
Prof Simon J Draper Department of Biochemistry University of Oxford South Parks Road Oxford United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Ally Olotu aolotu@ihi.or.tz +255718927104 Kingani
City Postal code Country Position/Affiliation
Bagamoyo United Republic of Tanzania Ifakara Health Institute
Role Name Email Phone Street address
Scientific Enquiries Enock Kessy ekessy@ihi.or.tz +255626837898 Kingani
City Postal code Country Position/Affiliation
Bagamoyo United Republic of Tanzania Ifakara Health Institute
Role Name Email Phone Street address
Public Enquiries Moshi Shabani mshabani@ihi.or.tz +255753726294 Kingani
City Postal code Country Position/Affiliation
Bagamoyo United Republic of Tanzania Ifakara health Institute
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes We plan to share the de-identified data on the parasite dynamics and safety of volunteers who participated in the study. This will be done during publication of the study results. Clinical Study Report within 12 months after study completion open Acess
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