Uncomplicated Falciparum MalariaPhase 2/3NCT04009343
Pharmacokinetics and Pharmacodynamics of the Gametocytocidal and Post-treatment Chemoprotective Effects of Antimalarials
A Phase 2/3 study testing Artemether-lumefantrine and Dihydroartemisinin-piperaquine in people with Uncomplicated Falciparum Malaria, run by Johns Hopkins Bloomberg School of Public Health at 1 site in Zambia.
Trial summary
Single-center phase II/III clinical investigation of the pharmacokinetics and pharmacodynamics of artemether-lumefantrine and dihydroartemisinin-piperaquine for gametocyte clearance and post-treatment chemoprotection in Zambian children with uncomplicated falciparum malaria. Read more about this study
- Who is it for?
- Ages 6 to 59 months
- Conditions the study is for
- Uncomplicated Falciparum Malaria
- What is being tested?
- Artemether-lumefantrine and Dihydroartemisinin-piperaquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 182 participants
- Where
- 1 siteZambia
- Study dates
- 19 Jun 2019to Dec 2026
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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 6 to 59 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Weight ≥10 kg
- Any indication for malaria diagnostic testing as determined by a treating provider (e.g., fever or history of fever)
- P. falciparum parasitemia (by microscopy) of any density not meeting criteria for severe malaria
- Ability to swallow oral medication
- Ability and willingness of parents or guardians to comply with study protocol for the duration of the study and to comply with the study follow-up visit schedule
- Residence within hospital catchment area
- Signed informed consent obtained from a legal representative of the participant
Who cannot join
- Complicated or severe falciparum malaria as defined by WHO criteria
- Hemoglobin concentration < 7 g/dL
- Use of any drug with antimalarial activity within the prior 4 weeks
- History of hypersensitivity reaction or intolerance to AL or DP
- Co-infection with Plasmodium spp. other than P. falciparum as determined by microscopy
- Confirmed or suspected concurrent acute infection other than malaria (e.g. measles, acute lower respiratory tract infection)
Show all 12Show fewer
- Current therapy with QT interval-prolonging agents
- Family history of sudden cardiac death or personal history of cardiac disease
- Residence outside the study area, or plan to leave the study area
- Residence in foster care or otherwise under government supervision
- Previous enrollment in the study, or enrollment in any other investigational drug trial during the previous 30 days
- Presence of any other condition or abnormality that in the opinion of the investigator would compromise the safety of the participant or the quality of the data
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Field Study of the Pharmacokinetics and Pharmacodynamics of Artemisinin-based Combination Therapy for Gametocyte Clearance and Post-treatment Chemoprotection in Zambian Children With Uncomplicated Falciparum Malaria
Single-center phase II/III clinical investigation of the pharmacokinetics and pharmacodynamics of artemether-lumefantrine and dihydroartemisinin-piperaquine for gametocyte clearance and post-treatment chemoprotection in Zambian children with uncomplicated falciparum malaria.
Read the detailed description
Artemisinin-based combination therapies (ACTs) are the first-line agents for uncomplicated falciparum malaria. Artemether-lumefantrine (AL) is the most widely adopted ACT in sub-Saharan Africa for case management. Dihydroartemisinin-piperaquine (DP) is increasingly used for mass drug administration in malaria eliminating regions, and is being explored as a candidate for intermittent preventive therapy. AL and DP possess similar clinical efficacy against uncomplicated falciparum malaria in areas of drug susceptible parasites. However, AL appears to clear gametocytes (the transmissible stage of the malaria parasite) more rapidly than DP, while DP confers a longer duration of post-treatment protection against reinfection. It is not known whether the observed difference in gametocyte clearance between AL and DP is due to pharmacokinetic (PK) and/or pharmacodynamic (PD) differences of the artemisinin derivatives, PK/PD features of the non-artemisinin companions, or contributions from both. The longer duration of protection against reinfection provided by DP is due to the long elimination half-life of the partner drug, but further characterization of its relative benefit in high-transmission settings compared to AL is needed to inform malaria drug policy. The investigators are conducting a single-center randomized controlled clinical trial comparing the efficacies of AL and DP for gametocyte clearance and post-treatment chemoprotection among 6- to 59-month-old children with uncomplicated falciparum malaria in a high malaria transmission area of northern Zambia. Children with microscopy-confirmed Plasmodium falciparum monoinfection will be admitted for 72 hours for directly observed therapy with either AL or DP and serial sampling for parasite clearance and multi-dose PK measurements. Twenty children from each arm will be recruited to an intensive PK subgroup. Participants will be followed for 9 weeks for outcome assessment according to World Health Organization-defined clinical endpoints and to measure clearance of the long-acting partner drugs. Parasite genotyping will be done to distinguish recrudescence from reinfection and query genetic markers of drug resistance. Participants will contribute fecal specimens to help investigate bidirectional associations between the intestinal microbiota and antimalarial drug pharmacokinetics, as well as enterotype association with risk of reinfection.
- Conditions
- Uncomplicated Falciparum Malaria
- Being tested
- Artemether-lumefantrine, Dihydroartemisinin-piperaquine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artemether-lumefantrineDrug
Also called Coartem®
Children will receive artemether-lumefantrine (20/120 mg) dosed according to weight (5 to <15 kg: 1 tablet, 15 to <25 kg: 2 tablets) at 0, 8, 24, 36, 48 and 60 hours. Medications will be administered according to the manufacturer's instructions.
Dihydroartemisinin-piperaquineDrug
Also called D-Artepp®
Children will receive dihydroartemisinin-piperaquine (40/320 mg) dosed according to weight (5 to <8 kg: 1/2 tablet, 8 to <11 kg: 3/4 tablet, 11 to <17 kg: 1 tablet, 17 to <25 kg: 1 1/2 tablets) at 0, 24, and 48 hours. Medications will be administered according to the manufacturer's instructions.
| Study group | Role | What they receive |
|---|---|---|
| Artemether-lumefantrine | Active comparator | Standard 6-dose regimen Receives: Drug: Artemether-lumefantrine |
| Dihydroartemisinin-piperaquine | Experimental | Standard 3-dose regimen Receives: Drug: Dihydroartemisinin-piperaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment outcome
Defined according to World Health Organization (WHO) classification as adequate clinical and parasitological response, early treatment failure, late clinical failure, or late parasitological failure corrected by genotyping to distinguish reinfection from recrudescent infection.
Measured: 9 weeks
Area-under-the-curve (AUC) of the gametocyte concentration-time curve
Primary gametocyte-related pharmacodynamic (PD) endpoint of the study
Measured: 72 hours
Incidence of reinfection during the 9-week follow-up period
Primary measure of the post-treatment chemoprotective effect of the drugs
Measured: 9 weeks
Secondary outcomes (5)
Elimination half-life of the gametocyte concentration-time curve
Alternative PD outcome of gametocyte dynamics
Measured: 72 hours up to 9 weeks for those with persistent gametocytemia
Change over time of the gametocyte sex ratio (female:male)
The ratio of female and male gametocytes over time during treatment is a hypothesized marker of transmissibility
Measured: 72 hours up to 9 weeks for those with persistent, emergent, or recurrent gametocytes
Elimination half-life of the asexual parasite concentration-time curve
In addition to gametocyte dynamics, asexual parasite dynamics and how they relate to PK parameters and other covariates with also be examined
Measured: 72 hours
Allele frequency of genetic markers of parasite drug resistance in initial vs. recurrent parasites and fast vs. slow clearing parasites
Relative barriers to drug resistance of AL and DP will be tested using known and newly described parasite genetic markers of resistance and association with phenotypic susceptibility
Measured: 9 weeks
Incidence of treatment-emergent adverse events (safety and tolerability)
We will assess adverse events and serious adverse events associated with the study drugs in accordance with the WHO Toxicity Grading Scale for Determining the Severity of Adverse Events
Measured: 9 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2019
- Study start19 Jun 2019
- Primary completion24 Aug 2020
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uncomplicated Falciparum MalariaStudies of the same condition, open and under way.
- More trials run by Johns Hopkins Bloomberg School of Public HealthThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 182 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins Bloomberg School of Public Health
- Sponsor type
- University, hospital or other
- Collaborators
- Tropical Diseases Research Centre
- Responsible party
- Sponsor
- Investigators
- William J Moss, MD MPH, Principal investigator, Johns Hopkins Bloomberg School of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04009343
- Sponsor's protocol ID
- IRB00007663
- Status last verified
- Dec 2025
- First submitted
- 7 Jun 2019
- Last updated
- 17 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data will be made available to other researchers upon reasonable request. Parasite clearance and drug resistance data will be contributed to the Worldwide Antimalarial Resistance Network database.
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Field Study of the Pharmacokinetics and Pharmacodynamics of Artemisinin-based Combination Therapy for Gametocyte Clearance and Post-treatment Chemoprotection in Zambian Children With Uncomplicated Falciparum Malaria
- ClinicalTrials.gov ID
- NCT04009343
- Acronym / sponsor ID
- IRB00007663
- Conditions
- Uncomplicated Falciparum Malaria
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 182 participants (estimated)
- Lead sponsor
- Johns Hopkins Bloomberg School of Public HealthUniversity, hospital or other
- Collaborators
- Tropical Diseases Research Centre
- Study start
- 19 Jun 2019 (actual)
- Primary completion
- 24 Aug 2020 (actual)
- Study completion
- Dec 2026 (estimated)
- First posted
- 5 Jul 2019 (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.
Single-center phase II/III clinical investigation of the pharmacokinetics and pharmacodynamics of artemether-lumefantrine and dihydroartemisinin-piperaquine for gametocyte clearance and post-treatment chemoprotection in Zambian children with uncomplicated falciparum malaria.
Detailed description
Artemisinin-based combination therapies (ACTs) are the first-line agents for uncomplicated falciparum malaria. Artemether-lumefantrine (AL) is the most widely adopted ACT in sub-Saharan Africa for case management. Dihydroartemisinin-piperaquine (DP) is increasingly used for mass drug administration in malaria eliminating regions, and is being explored as a candidate for intermittent preventive therapy. AL and DP possess similar clinical efficacy against uncomplicated falciparum malaria in areas of drug susceptible parasites. However, AL appears to clear gametocytes (the transmissible stage of the malaria parasite) more rapidly than DP, while DP confers a longer duration of post-treatment protection against reinfection. It is not known whether the observed difference in gametocyte clearance between AL and DP is due to pharmacokinetic (PK) and/or pharmacodynamic (PD) differences of the artemisinin derivatives, PK/PD features of the non-artemisinin companions, or contributions from both. The longer duration of protection against reinfection provided by DP is due to the long elimination half-life of the partner drug, but further characterization of its relative benefit in high-transmission settings compared to AL is needed to inform malaria drug policy. The investigators are conducting a single-center randomized controlled clinical trial comparing the efficacies of AL and DP for gametocyte clearance and post-treatment chemoprotection among 6- to 59-month-old children with uncomplicated falciparum malaria in a high malaria transmission area of northern Zambia. Children with microscopy-confirmed Plasmodium falciparum monoinfection will be admitted for 72 hours for directly observed therapy with either AL or DP and serial sampling for parasite clearance and multi-dose PK measurements. Twenty children from each arm will be recruited to an intensive PK subgroup. Participants will be followed for 9 weeks for outcome assessment according to World Health Organization-defined clinical endpoints and to measure clearance of the long-acting partner drugs. Parasite genotyping will be done to distinguish recrudescence from reinfection and query genetic markers of drug resistance. Participants will contribute fecal specimens to help investigate bidirectional associations between the intestinal microbiota and antimalarial drug pharmacokinetics, as well as enterotype association with risk of reinfection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Artemether-lumefantrine | Active comparator | Drug: Artemether-lumefantrineStandard 6-dose regimen |
| Dihydroartemisinin-piperaquine | Experimental | Drug: Dihydroartemisinin-piperaquineStandard 3-dose regimen |
Who may qualify
- Ages
- 6 to 59 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Weight ≥10 kg
- Any indication for malaria diagnostic testing as determined by a treating provider (e.g., fever or history of fever)
- P. falciparum parasitemia (by microscopy) of any density not meeting criteria for severe malaria
- Ability to swallow oral medication
- Ability and willingness of parents or guardians to comply with study protocol for the duration of the study and to comply with the study follow-up visit schedule
Key exclusion criteria (12 listed)
- Complicated or severe falciparum malaria as defined by WHO criteria
- Hemoglobin concentration < 7 g/dL
- Use of any drug with antimalarial activity within the prior 4 weeks
- History of hypersensitivity reaction or intolerance to AL or DP
- Co-infection with Plasmodium spp. other than P. falciparum as determined by microscopy
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 |
|---|---|---|
| Artemether-lumefantrineAlso: Coartem®Children will receive artemether-lumefantrine (20/120 mg) dosed according to weight (5 to <15 kg: 1 tablet, 15 to <25 kg: 2 tablets) at 0, 8, 24, 36, 48 and 60 hours. Medications will be administered according to the manufacturer's instructions. | Drug | Artemether-lumefantrine |
| Dihydroartemisinin-piperaquineAlso: D-Artepp®Children will receive dihydroartemisinin-piperaquine (40/320 mg) dosed according to weight (5 to <8 kg: 1/2 tablet, 8 to <11 kg: 3/4 tablet, 11 to <17 kg: 1 tablet, 17 to <25 kg: 1 1/2 tablets) at 0, 24, and 48 hours. Medications will be administered according to the manufacturer's instructions. | Drug | Dihydroartemisinin-piperaquine |
Primary outcome
Treatment outcome
Time frame: 9 weeks
Defined according to World Health Organization (WHO) classification as adequate clinical and parasitological response, early treatment failure, late clinical failure, or late parasitological failure corrected by genotyping to distinguish reinfection from recrudescent infection.
Area-under-the-curve (AUC) of the gametocyte concentration-time curve
Time frame: 72 hours
Primary gametocyte-related pharmacodynamic (PD) endpoint of the study
Incidence of reinfection during the 9-week follow-up period
Time frame: 9 weeks
Primary measure of the post-treatment chemoprotective effect of the drugs
5 secondary outcomes
Elimination half-life of the gametocyte concentration-time curve
Time frame: 72 hours up to 9 weeks for those with persistent gametocytemia
Change over time of the gametocyte sex ratio (female:male)
Time frame: 72 hours up to 9 weeks for those with persistent, emergent, or recurrent gametocytes
Elimination half-life of the asexual parasite concentration-time curve
Time frame: 72 hours
Allele frequency of genetic markers of parasite drug resistance in initial vs. recurrent parasites and fast vs. slow clearing parasites
Time frame: 9 weeks
Incidence of treatment-emergent adverse events (safety and tolerability)
Time frame: 9 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2025.
- Individual participant dataSharing planned: Yes. Individual participant data will be made available to other researchers upon reasonable request. Parasite clearance and drug resistance data will be contributed to the Worldwide Antimalarial Resistance Network database.
Related trials for Uncomplicated Falciparum Malaria
RecruitingPhase 2
Platform Study to Evaluate the Efficacy and Safety of Anti-malarial Agents in Participants With Uncomplicated Plasmodium Falciparum Malaria (Cohort C2)
Uncomplicated Plasmodium Falciparum Malaria
Not yet recruitingObservational study
Ethiopian Antimalarial Therapeutic Efficacy Study 2026
Plasmodium Vivax Malaria Without Complication, Plasmodium Falciparum Malaria (Uncomplicated)
Not yet recruitingPhase 4
Study to Assess Safety and Clinical Responses With Coartem® Baby Dispersible Tablets in Paediatric Patients Weighing 2 to <5 kg With Uncomplicated Malaria
Malaria
Not yet recruitingPhase 2
A Phase 2A Study of a Novel Antimalarial Pyrrolidinamide in Adult Patients With Uncomplicated P. Falciparum Malaria
Malaria, Falciparum
RecruitingPhase 2
Safety and Efficacy of Imatinib in Combination With Artemether-Lumefantrine for Uncomplicated Malaria
Malaria (Plasmodium Falciparum)
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.
William J Moss, MD MPH principal investigator
Johns Hopkins Bloomberg School of Public Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Artemether-lumefantrine and Dihydroartemisinin-piperaquine in people with Uncomplicated Falciparum Malaria, run by Johns Hopkins Bloomberg School of Public Health at 1 site in Zambia.
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 7 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 17 Dec 2025. 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 Zambia. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment outcome (time frame: 9 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Dec 2025.