Gametocytocidal and Transmission-blocking Efficacy of PQ in Combination With AL and TQ in Combination With SPAQ in Mali
- Conditions
- Malaria,Falciparum
- Interventions
- Registration Number
- NCT05081089
- Lead Sponsor
- London School of Hygiene and Tropical Medicine
- Brief Summary
The purpose of this study is to compare the gametocytocidal and transmission reducing activity of artemether-lumefantrine (AL) with and without a single dose of 0.25mg/kg primaquine (PQ) and sulfadoxine-pyrimethamine with amodiaquine (SPAQ) with and without single dose of 1.66mg/kg tafenoquine (TQ). Outcome measures will include infectivity to mosquitoes at 2, 5 and 7 days after treatment, gametocyte density throughout follow-up, and safety measures including haemoglobin density and the frequency of adverse events.
- Detailed Description
Full protocol available on request.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 80
- Age ≥ 10 years and ≤ 50 years
- G6PD-normal defined by Carestart rapid diagnostic test or the OSMMR2000 G6PD qualitative test
- Absence of symptomatic falciparum malaria, defined by fever on enrolment
- Presence of P. falciparum gametocytes on thick blood film at a density >16 gametocytes/μL (i.e. ≥ gametocytes recorded in the thick film against 500 white blood cells)
- Absence of other non-P. falciparum species on blood film
- Hemoglobin ≥ 10 g/dL
- Individuals weighing < = 80 kg
- No evidence of acute severe or chronic disease
- Written, informed consent
- Women who are pregnant or lactating (tested at baseline). Urine and/or serum pregnancy testing (β-hCG) will be used.
- Detection of a non-P. falciparum species by microscopy
- Previous reaction to study drugs / known allergy to study drugs
- Signs of severe malaria, including hyperparasitemia (defined as asexual parasitemia > 100,000 parasites / μL)
- Signs of acute or chronic illness, including hepatitis
- The use of other medication (except for paracetamol and/or aspirin)
- Use of antimalarial drugs over the past 7 days (as reported by the participant)
- Clinically significant illness (intercurrent illness e.g., pneumonia, pre-existing condition e.g., renal disease, malignancy or conditions that may affect absorption of study medication e.g., severe diarrhea or any signs of malnutrition as defined clinically)
- Signs of hepatic injury (such as nausea and/or abdominal pain associated with jaundice) or known severe liver disease (i.e., decompensated cirrhosis, Child Pugh stage B or C)
- Signs, symptoms or known renal impairment
- Clinically significant abnormal laboratory values as determined by history, physical examination or routine blood chemistries and hematology values (laboratory guideline values for exclusion are hemoglobin < 10 g/dL, platelets < 50,000/μl, White Blood Cell count (WBC) < 2000/μl, serum creatinine >2.0mg/dL, or ALT or AST more than 3 times the upper limit of normal for age.
- Blood transfusion in the last 90 days.
- Consistent with the long half-life of tafenoquine, effective contraception should be continued for 5 half-lives (3 months) after the end of treatment.
- History of psychiatric disorders
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AL with 0.25mg/kg primaquine (PQ) Primaquine Phosphate Subjects will receive artemether-lumefantrine (AL) twice daily for 3 days and a single dose of 0.25mg/kg primaquine (PQ) on the first day of AL treatment. Sulphadoxine-pyrimethamine with amodiaquine (SPAQ) Sulphadoxine-pyrimethamine with amodiaquine Subjects will receive sulphadoxine-pyrimethamine with amodiaquine (SPAQ) once daily for 3 days. SPAQ with 1.66mg/kg tafenoquine (TQ) Sulphadoxine-pyrimethamine with amodiaquine Subjects will receive sulphadoxine-pyrimethamine with amodiaquine (SPAQ) once daily for 3 days and a single dose of 1.66mg/kg tafenoquine (TQ) on the first day of SPAQ treatment. Artemether-lumefantrine (AL) Artemether-lumefantrine Subjects will receive artemether-lumefantrine (AL) twice daily for 3 days. AL with 0.25mg/kg primaquine (PQ) Artemether-lumefantrine Subjects will receive artemether-lumefantrine (AL) twice daily for 3 days and a single dose of 0.25mg/kg primaquine (PQ) on the first day of AL treatment. SPAQ with 1.66mg/kg tafenoquine (TQ) Tafenoquine Subjects will receive sulphadoxine-pyrimethamine with amodiaquine (SPAQ) once daily for 3 days and a single dose of 1.66mg/kg tafenoquine (TQ) on the first day of SPAQ treatment.
- Primary Outcome Measures
Name Time Method Change in mosquito infection rate assessed through membrane feeding assays (day 2 and day 7) 3 days (days 0, 2 and 7): 7 day span Within person percent change (presented as percent reduction) in mosquito infection rate in infectious individuals from baseline (day 0, pre-treatment) to day 2 post treatment in the AL and AL-PQ arms, and day 7 post-treatment in the SPAQ and SPAQ-TQ.
- Secondary Outcome Measures
Name Time Method Change in mosquito infection rate assessed through membrane feeding assays (all timepoints) 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span Within person percent change (presented as percent reduction) in mosquito infection rate from baseline to all feeding time-points, with comparison within and between arms.
Mosquito infection rate assessed through membrane feeding assays 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span Mosquito infection rate at all feeding time-points, with comparison within treatment arms compared to baseline, and between arms.
Mosquito infection density assessed through membrane feeding assays 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span Oocyst intensity (in all/all infected mosquitoes) at all feeding time-points, with comparison within treatment arms compared to baseline, and between arms.
Asexual/sexual stage parasite prevalence 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span Male and female gametocyte prevalence at all time-points, determined by microscopy or molecular assays, with comparison within treatment arms compared to baseline, and between arms.
Asexual and total parasite prevalence at all time-points, determined by microscopy or molecular assays, with comparison within treatment arms compared to baseline, and between arms.Haemoglobin density 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span Haemoglobin density (g/dL) at all time-points, with comparison within treatment arms compared to baseline, and between arms.
Human infectivity to locally reared mosquitoes assessed through membrane feeding assays 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span Infectivity to mosquitoes at all feeding time-points, with comparison within treatment arms compared to baseline, and between arms.
Gametocyte infectivity 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span Infectiousness to mosquitoes for a given gametocyte density (measured as mosquito infection rate/gametocyte) at all feeding time-points, with comparison within treatment arms compared to baseline, and between arms.
Asexual/sexual stage parasite density 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span Male and female gametocyte density at all time-points, determined by microscopy or molecular assays, with comparison within treatment arms compared to baseline, and between arms.
Asexual and total parasite density at all time-points, determined by microscopy or molecular assays, with comparison within treatment arms compared to baseline, and between arms.Sexual stage parasite sex ratio 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span Male and female gametocyte sex ratio (proportion male) at all time-points, determined by microscopy or molecular assays, with comparison within treatment arms compared to baseline, and between arms.
Sexual stage parasite circulation time 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span Gametocyte circulation time (cumulative), determined by microscopy or molecular assays, compared within and between treatment arms.
Sexual stage parasite area under the curve (AUC) 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span Gametocyte area under the curve (cumulative), determined by microscopy or molecular assays, compared within and between treatment arms.
Change in haemoglobin density 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span Within person percent change (presented as percent reduction) in haemoglobin density (g/dL) from baseline to all time-points, with comparison within and between arms.
Methaemoglobin density 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28) Methaemoglobin density (g/dL) at all time-points, with comparison within treatment arms compared to baseline, and between arms.
Incidence of adverse events 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span The frequency and prevalence of adverse events (all AE's, treatment related AE's, and haematological AE's) observed up to and including day 2, 7, and 14 post-treatment, and at all timepoints.
Change in methaemoglobin density 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span Within person percent change (presented as percent reduction) in methaemoglobin density (g/dL) from baseline to all time-points, with comparison within and between arms.
Trial Locations
- Locations (1)
Malaria Research and Training Centre
🇲🇱Bamako, Mali