Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
NOT_YET_RECRUITING
PHASE1
24 participants
INTERVENTIONAL
2024-01-09
2024-06-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
There is an urgent need to establish an in vivo model for early-stage clinical evaluation of transmission blocking interventions (TBI) in volunteers living in malaria endemic countries. This would allow rapid and cost-effective way to down-select transmission blocking candidate malaria vaccine and gametocidal antimalarial drugs before larger, more complex, and expensive field efficacy studies are conducted. A study done in naïve individual showed 100% success in establishing a malaria infection using 2800 P. falciparum infected RBCs, while a recent study (manuscript in development) has demonstrated success in establishing infection in Tanzanian semi-immune individuals with low malaria exposure using 1000 P. falciparum infected RBCs. We will use 1000 ALU-sensitive 3D7 P. falciparum infected RBCs to establish an in vivo transmission model for studying Transmission blocking interventions and assess the efficiency of two antimalarial drugs regimens (Piperaquine and doxycycline) to induce high levels of gametocytaemia and mosquito infection rates in healthy African adults. We will also investigate the determinants of successful transmission to mosquitoes including underlying immune responses to both asexual and sexual malaria antigens, asexual parasite dynamics and gametocyte burden, sex ratio of male and female gametocytes, and the relationship between gametocyte density and mosquito infection rate
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
This will be Phase I Randomized open label trial. It will recruit Healthy male adults aged 18-45 years from low malaria endemic area (Bagamoy0) for three months.
BACKGROUND AND RATIONALE Plasmodium falciparum (Pf) malaria remains a disease of public health significance affecting millions across the globe (1). Scaling up of malaria interventions has reduced the malaria burden in several parts of Africa (2-5), but this has not been consistent everywhere, with some areas reporting sustained or even an increase in the burden of malaria (6, 7). Vaccination is one of the most cost-effective public health interventions (8, 9) and would play a critical role in the elimination efforts. There is a significant development in research to identify promising transmission-blocking malaria vaccines, with several candidate vaccines in the pipeline. To down-select the most promising candidates, antibody tests and functional assays that prevent infection of mosquitoes are normally used (10). It is however unclear how well these assays represent the in vivo transmission-blocking efficacy making it difficult to choose which candidate to develop further (11). Before a transmission blocking vaccine (TBV) can be approved, a randomized trial to evaluate the effect on gametocyte carriage and transmission to mosquitoes or Phase 3 trial to demonstrate vaccine impact on the incidence of infection in the target population are required. Both study designs are large and expensive (11). Alternatively, accelerated approval could be sought through surrogate markers of efficacy that would require either analytical or biological, but not clinical validation. However currently there is no known surrogate markers. Therefore, 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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm1
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).
Piperaquine tablets , which will be administered orally as a single dose of 480mg (320mg+160mg).
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).
Arm 2
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.
Doxycycline (100mg tablets strength as Doxycycline Hyclate) will also be administered orally and will be given as 1 tablet (100mg) Once daily for 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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Piperaquine tablets , which will be administered orally as a single dose of 480mg (320mg+160mg).
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).
Doxycycline (100mg tablets strength as Doxycycline Hyclate) will also be administered orally and will be given as 1 tablet (100mg) Once daily for 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.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
Exclusion Criteria
* 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 skin), treated or untreated, within the past 5 years.
* Any history of treatment for severe psychiatric disease by a psychiatrist in the past year.
* History of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset.
* Previous participation in any malaria investigational product study (allowable time frame for use at the Investigator's discretion)
* Participation in any other clinical study in the 30 days prior to the start of the study or during the study period.
* Being an employee or relative of an employee of Ifakara Health Institute.
* Current participation in another clinical trial or recent participation within 12 weeks of enrolment.
* Prior receipt of an investigational malaria vaccine.
* Previous receipt of malaria sporozoites (PfSPZ) or infected RBC as part of the malaria challenge study.
* Use of immunoglobulins or blood products within 3 months prior to enrolment.
* Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination.
* Confirmed parasite positive by qPCR at screening (can be treated and rescreened if time allows)
* History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
* Any history of treatment for severe psychiatric disease by a psychiatrist in the past year.
* History of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset.
* Known hypersensitivity to or contra-indications (including co-medication) for use of Piperaquine, doxycycline, chloroquine, primaquine, artemether-lumefantrine or history of severe (allergic) reactions to blood transfusion.
* Any other condition or situation that would, in the opinion of the investigator, place the volunteer at an unacceptable risk of injury or render the volunteer unable to meet the requirements of the protocol
18 Years
45 Years
MALE
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
University of Oxford
OTHER
Ifakara Health Institute
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Ally Olotu, MD,Dphil
Role: PRINCIPAL_INVESTIGATOR
Ifakara Health Institute
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Ifakara Health Institute
Pwani, , Tanzania
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Ally Olotu, MD,DPhil
Role: primary
Enock Kessy, BSc,MSc
Role: backup
References
Explore related publications, articles, or registry entries linked to this study.
Aregawi MW, Ali AS, Al-mafazy AW, Molteni F, Katikiti S, Warsame M, Njau RJ, Komatsu R, Korenromp E, Hosseini M, Low-Beer D, Bjorkman A, D'Alessandro U, Coosemans M, Otten M. Reductions in malaria and anaemia case and death burden at hospitals following scale-up of malaria control in Zanzibar, 1999-2008. Malar J. 2011 Feb 18;10:46. doi: 10.1186/1475-2875-10-46.
Ceesay SJ, Casals-Pascual C, Nwakanma DC, Walther M, Gomez-Escobar N, Fulford AJ, Takem EN, Nogaro S, Bojang KA, Corrah T, Jaye MC, Taal MA, Sonko AA, Conway DJ. Continued decline of malaria in The Gambia with implications for elimination. PLoS One. 2010 Aug 18;5(8):e12242. doi: 10.1371/journal.pone.0012242.
Farnert A, Yman V, Homann MV, Wandell G, Mhoja L, Johansson M, Jesaja S, Sandlund J, Tanabe K, Hammar U, Bottai M, Premji ZG, Bjorkman A, Rooth I. Epidemiology of malaria in a village in the Rufiji River Delta, Tanzania: declining transmission over 25 years revealed by different parasitological metrics. Malar J. 2014 Nov 26;13:459. doi: 10.1186/1475-2875-13-459.
Okiro EA, Hay SI, Gikandi PW, Sharif SK, Noor AM, Peshu N, Marsh K, Snow RW. The decline in paediatric malaria admissions on the coast of Kenya. Malar J. 2007 Nov 15;6:151. doi: 10.1186/1475-2875-6-151.
Assele V, Ndoh GE, Nkoghe D, Fandeur T. No evidence of decline in malaria burden from 2006 to 2013 in a rural Province of Gabon: implications for public health policy. BMC Public Health. 2015 Feb 4;15:81. doi: 10.1186/s12889-015-1456-4.
Okiro EA, Bitira D, Mbabazi G, Mpimbaza A, Alegana VA, Talisuna AO, Snow RW. Increasing malaria hospital admissions in Uganda between 1999 and 2009. BMC Med. 2011 Apr 13;9:37. doi: 10.1186/1741-7015-9-37.
Holden JD. Benefits and risks of childhood immunisations in developing countries. Br Med J (Clin Res Ed). 1987 May 23;294(6583):1329-31. doi: 10.1136/bmj.294.6583.1329.
Robertson RL, Foster SO, Hull HF, Williams PJ. Cost-effectiveness of immunization in The Gambia. J Trop Med Hyg. 1985 Oct;88(5):343-51.
Miura K, Swihart BJ, Deng B, Zhou L, Pham TP, Diouf A, Burton T, Fay MP, Long CA. Transmission-blocking activity is determined by transmission-reducing activity and number of control oocysts in Plasmodium falciparum standard membrane-feeding assay. Vaccine. 2016 Jul 29;34(35):4145-4151. doi: 10.1016/j.vaccine.2016.06.066. Epub 2016 Jun 29.
Related Links
Access external resources that provide additional context or updates about the study.
World Health O. World malaria report 2019. Geneva: World Health Organization; 2019 2019
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
Blood-CHMI Trans
Identifier Type: -
Identifier Source: org_study_id