Controlled Human Malaria InfectionPhase 1NCT06172686
In-vivo Transmission Model in Semi-immune Adults
A Phase 1 study testing Piperaquine tablets , which will be administered orally as a single dose of 480mg (320mg+160mg). and 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. in people with Controlled Human Malaria Infection and Induced Blood Stage Malaria Infection, run by Ifakara Health Institute at 1 site in Tanzania.
Trial summary
Controlled human malaria infection (CHMI) has revolutionized the development of malaria vaccines. It involves the administration of either known numbers of sporozoites or infected erythrocytes to healthy human volunteers under a controlled environment. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Controlled Human Malaria Infection, Induced Blood Stage Malaria Infection, Malaria Transmission
- What is being tested?
- Piperaquine tablets , which will be administered orally as a single dose of 480mg (320mg+160mg). and 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.
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteTanzania
- Study dates
- 9 Jan 2024to 30 Jun 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 26Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Tanzania1 site
Ifakara Health Institute
Pwani
Ally Olotu, MD,DPhil, +255 718 927 104, aolotu@ihi.or.tz
Enock Kessy, BSc,MSc, +255 626 837 898, ekessy@ihi.or.tz
About this study
Official title: Adaptation of Blood-stage Controlled Human Malaria Infection for Evaluation of Transmission Blocking Malaria Interventions in Malaria Endemic Countries
Controlled human malaria infection (CHMI) has revolutionized the development of malaria vaccines. It involves the administration of either known numbers of sporozoites or infected erythrocytes to healthy human volunteers under a controlled environment. The use of highly sensitive molecular malaria diagnostic methods informs treatment decisions before symptom development and allows the characterization of parasite growth dynamics. Sporozoite CHMI has safely been used in six countries in Africa providing a platform to assess the efficacy of candidate malaria vaccines and study the natural immunity to malaria. Blood stage CHMI involves administration of known number of Artemether Lumefantrine sensitive infected erythrocytes in healthy volunteers, and it is a more sensitive model for modelling parasite growths and study the efficacy of blood-stage malaria vaccines. It has been safely used in Australia and Europe but not in Africa. Adaptation of this model by administration of combination of suboptimal and optimal antimalarial drugs lead to increased gametocytaemia, and infection rates in mosquitoes following standard membrane feeding assay. Such adaptation allows the model to be used to study parasite transmission from human to mosquitoes and evaluate transmission blocking malaria interventions.
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
Read the detailed description
Adaptation of blood-stage Controlled Human Malaria Infection for evaluation of transmission blocking malaria interventions in malaria endemic countries.
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
- Controlled Human Malaria Infection, Induced Blood Stage Malaria Infection, Malaria Transmission, Malaria Challenge
- Being tested
- Piperaquine tablets , which will be administered orally as a single dose of 480mg (320mg+160mg)., 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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Piperaquine tablets , which will be administered orally as a single dose of 480mg (320mg+160mg).Drug
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.Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm1 | Experimental | 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). Receives: Drug: Piperaquine tablets , which will be administered orally as a single dose of 480mg (320mg+160mg). |
| Arm 2 | Experimental | 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. Receives: Drug: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Solicited and unsolicited adverse events
Frequency of solicited and unsolicited adverse events.
Measured: Up to day 98 after blood infection challenge.
Magnitude of Adverse Events
Magnitude of Adverse Events both solicitated and Unsolicited
Measured: Up to day 98 after blood infection challenge.
Secondary outcomes (7)
Rate of Mosquito infections (proportion of infected mosquitoes)
Rate of Mosquito infections (proportion of infected mosquitoes)
Measured: 14, 21 and 28 days after infection challenge
Infection burden (Oocysts density in infected mosquitoes)
Infection burden (Oocysts density in infected mosquitoes)
Measured: 14, 21 and 28 days after infection challenge
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.
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.
Measured: Up to day 28 after blood infection challenge
Time to peak density gametocytes from the time of challenge as measured by qRT-PCR.
Time to peak density gametocytes from the time of challenge as measured by qRT-PCR.
Measured: Up to day 28 after the blood infection challenge
The area under the curve of gametocyte density versus time for both arms of the study
The area under the curve of gametocyte density versus time for both arms of the study
Measured: Up to day 28 after the blood infection challenge
Gametocyte commitment after the blood infection challenge as estimated by dividing the peak gametocyte by the peak of asexual parasites
Gametocyte commitment after the blood infection challenge as estimated by dividing the peak gametocyte by the peak of asexual parasites
Measured: Up to day 28 after the blood infection challenge
Gametocyte Sex-ratio after blood infection challenge as measured by the proportion of male gametocytes versus female gametocytes.
Gametocyte Sex-ratio after blood infection challenge as measured by the proportion of male gametocytes versus female gametocytes.
Measured: Up to day 28 after the blood infection challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2023
- Study start9 Jan 2024 (estimated)
- Primary completion13 Feb 2024 (estimated)
- Study completion30 Jun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Controlled Human Malaria InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two antimalarial drugs will be used to induce gametocytes. The first arm will receive Piperaquine tablets (Piramal Pharma Solutions, India), that will be administered orally. Sub-curative regimen will be given as two tablets of 320mg and 160mg (total of 480mg). 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.
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ifakara Health Institute
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oxford
- Responsible party
- Sponsor
- Investigators
- Ally Olotu, MD,Dphil, Principal investigator, Ifakara Health Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06172686
- Sponsor's protocol ID
- Blood-CHMI Trans
- Status last verified
- Dec 2023
- First submitted
- 7 Dec 2023
- Last updated
- 15 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Publications
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.
PubMed 21332989Ceesay 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.
PubMed 20805878Farnert 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.
PubMed 25423887Okiro 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.
PubMed 18005422Assele 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.
PubMed 25649228Okiro 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.
PubMed 21486498Holden 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.
PubMed 3109642Robertson RL, Foster SO, Hull HF, Williams PJ. Cost-effectiveness of immunization in The Gambia. J Trop Med Hyg. 1985 Oct;88(5):343-51.
PubMed 3939146Miura 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.
PubMed 27372156
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adaptation of Blood-stage Controlled Human Malaria Infection for Evaluation of Transmission Blocking Malaria Interventions in Malaria Endemic Countries
- ClinicalTrials.gov ID
- NCT06172686
- Acronym / sponsor ID
- Blood-CHMI Trans
- Conditions
- Controlled Human Malaria Infection, Induced Blood Stage Malaria Infection, Malaria Transmission, Malaria Challenge
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Ifakara Health InstituteUniversity, hospital or other
- Collaborators
- University of Oxford
- Study start
- 9 Jan 2024 (estimated)
- Primary completion
- 13 Feb 2024 (estimated)
- Study completion
- 30 Jun 2024 (estimated)
- First posted
- 15 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Controlled human malaria infection (CHMI) has revolutionized the development of malaria vaccines. It involves the administration of either known numbers of sporozoites or infected erythrocytes to healthy human volunteers under a controlled environment. The use of highly sensitive molecular malaria diagnostic methods informs treatment decisions before symptom development and allows the characterization of parasite growth dynamics. Sporozoite CHMI has safely been used in six countries in Africa providing a platform to assess the efficacy of candidate malaria vaccines and study the natural immunity to malaria. Blood stage CHMI involves administration of known number of Artemether Lumefantrine sensitive infected erythrocytes in healthy volunteers, and it is a more sensitive model for modelling parasite growths and study the efficacy of blood-stage malaria vaccines. It has been safely used in Australia and Europe but not in Africa. Adaptation of this model by administration of combination of suboptimal and optimal antimalarial drugs lead to increased gametocytaemia, and infection rates in mosquitoes following standard membrane feeding assay. Such adaptation allows the model to be used to study parasite transmission from human to mosquitoes and evaluate transmission blocking malaria interventions.
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
Adaptation of blood-stage Controlled Human Malaria Infection for evaluation of transmission blocking malaria interventions in malaria endemic countries.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Two antimalarial drugs will be used to induce gametocytes. The first arm will receive Piperaquine tablets (Piramal Pharma Solutions, India), that will be administered orally. Sub-curative regimen will be given as two tablets of 320mg and 160mg (total of 480mg). 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.
| Arm | Type | Receives |
|---|---|---|
| Arm1 | Experimental | Drug: 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 | Experimental | Drug: 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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). | Drug | Arm1 |
| 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. | Drug | Arm 2 |
Primary outcome
Solicited and unsolicited adverse events
Time frame: Up to day 98 after blood infection challenge.
Frequency of solicited and unsolicited adverse events.
Magnitude of Adverse Events
Time frame: Up to day 98 after blood infection challenge.
Magnitude of Adverse Events both solicitated and Unsolicited
7 secondary outcomes
Rate of Mosquito infections (proportion of infected mosquitoes)
Time frame: 14, 21 and 28 days after infection challenge
Infection burden (Oocysts density in infected mosquitoes)
Time frame: 14, 21 and 28 days after infection challenge
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.
Time frame: Up to day 28 after blood infection challenge
Time to peak density gametocytes from the time of challenge as measured by qRT-PCR.
Time frame: Up to day 28 after the blood infection challenge
The area under the curve of gametocyte density versus time for both arms of the study
Time frame: Up to day 28 after the blood infection challenge
Gametocyte commitment after the blood infection challenge as estimated by dividing the peak gametocyte by the peak of asexual parasites
Time frame: Up to day 28 after the blood infection challenge
Gametocyte Sex-ratio after blood infection challenge as measured by the proportion of male gametocytes versus female gametocytes.
Time frame: Up to day 28 after the blood infection challenge
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2023.
- Background: PubMed 21332989Aregawi 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.
- Background: PubMed 20805878Ceesay 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.
- Background: PubMed 25423887Farnert 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.
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- World Health O. World malaria report 2019. Geneva: World Health Organization; 2019 2019Link provided by the sponsor.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ally Olotu, MD,Dphil principal investigator
Ifakara Health Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Piperaquine tablets , which will be administered orally as a single dose of 480mg (320mg+160mg). and 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. in people with Controlled Human Malaria Infection and Induced Blood Stage Malaria Infection, run by Ifakara Health Institute at 1 site in Tanzania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ally Olotu, MD,Dphil (+255 718 927 104, aolotu@ihi.or.tz), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Solicited and unsolicited adverse events (time frame: Up to day 98 after blood infection challenge.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06172686, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2023.