Clinical trial NCT05081089: Gametocytocidal and Transmission-blocking Efficacy of PQ in Combination With AL and TQ in Combination With SPAQ in Mali
Official title: A Four-arm Trial Comparing Artemether-lumefantrine With or Without Single-dose Primaquine and Sulphadoxine-pyrimethamine/Amodiaquine With or Without Single-dose Tafenoquine to Reduce P. Falciparum Transmission in Mali
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria,Falciparum
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
First posted: 2021-10-18
Enrollment: 80
Sex: ALL
Minimum age (years): 10
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change in mosquito infection rate assessed through membrane feeding assays (day 2 and day 7)
timeFrame: 3 days (days 0, 2 and 7): 7 day span
Secondary outcomes:
measure: Change in mosquito infection rate assessed through membrane feeding assays (all timepoints)
timeFrame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
measure: Mosquito infection rate assessed through membrane feeding assays
timeFrame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
measure: Human infectivity to locally reared mosquitoes assessed through membrane feeding assays
timeFrame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
measure: Mosquito infection density assessed through membrane feeding assays
timeFrame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
measure: Gametocyte infectivity
timeFrame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
measure: Asexual/sexual stage parasite prevalence
timeFrame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
measure: Asexual/sexual stage parasite density
timeFrame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
measure: Sexual stage parasite sex ratio
timeFrame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
measure: Sexual stage parasite circulation time
timeFrame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
measure: Sexual stage parasite area under the curve (AUC)
timeFrame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
measure: Haemoglobin density
timeFrame: 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
measure: Change in haemoglobin density
timeFrame: 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
measure: Methaemoglobin density
timeFrame: 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28)
measure: Change in methaemoglobin density
timeFrame: 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
measure: Incidence of adverse events
timeFrame: 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
Other outcomes:
measure: Parasite genomic and transcriptomic variation assessed in RNA
timeFrame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
measure: The impact of plasma biomarkers on malaria transmission efficiency
timeFrame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
measure: Human genomic variation analysis and association with parasite measure
timeFrame: day 0
measure: ALT/AST/Creatine density
timeFrame: 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
Locations:
city: Bamako
country: Mali
facility: Malaria Research and Training Centre
Study officials:
affiliation: Malaria Research and Training Centre, Mali
name: Alassane Dicko
role: PRINCIPAL_INVESTIGATOR
References: