Clinical trial NCT04609098: Single Low Dose Tafenoquine to Reduce P. Falciparum Transmission in Mali (NECTAR2)
Official title: Single Low Dose Tafenoquine to Reduce P. Falciparum Transmission in Mali (NECTAR2)
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: 2020-10-30
Enrollment: 80
Sex: ALL
Minimum age (years): 12
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 assess the gametocytocidal and transmission reducing activity of dihydroartemisinin-piperaquine (DP) with and without various low doses of tafenoquine (TQ; 1.66mg/kg, 0.83mg/kg, or 0.415mg/kg). Outcome measures will include infectivity to mosquitoes at 2 and 7 days after treatment, gametocyte density throughout follow-up, and safety measures including haemoglobin density.

Detailed description: Full protocol available on request.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 12 years and ≤ 50 years
* Glucose 6 phosphate dehydrogenase (G6PD) normal status defined by Carestart rapid diagnostic test or the G6PD qualitative test (OSMMR2000)
* 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
* No allergies to study drugs
* No use of antimalarial drugs over the past 7 days (as reported by the participant)
* Hemoglobin ≥ 10 g/dL
* Individuals weighing \< = 80 kg
* No evidence of acute severe or chronic disease
* Written, informed consent

Exclusion Criteria:

* Age \< 12 years or \> 50 years
* Women who are pregnant or lactating
* Blood thick film negative for sexual stages of malaria
* 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 (with the exception of paracetamol and/or aspirin)
* Consent not given
* G6PD-deficiency by Carestart rapid diagnostic test or the OSMMR2000 G6PD qualitative test
* Use of antimalarial drugs over the past 7 days (as reported by the participant)
* The use of other medication (with the exception of paracetamol and/or aspirin)
* 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.
* Family history of diseases leading to QT prolongation or recent treatment with drugs linked to QT prolongation
* 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 infectivity assessed through membrane feeding assays (day 7)
timeFrame: 2 days (Days 0 & 7): 7 day span
Secondary outcomes:
measure: Change in mosquito infectivity assessed through membrane feeding assays (days 2 and 14)
timeFrame: 3 days (Days 0, 2, & 14): 14 day span
measure: Mosquito infection density assessed through membrane feeding assays
timeFrame: 4 days (Days 0, 2, 7 & 14): 14 day span
measure: Mosquito infection prevalence assessed through membrane feeding assays
timeFrame: 4 days (Days 0, 2, 7 & 14): 14 day span
measure: Human infectivity assessed through membrane feeding assays
timeFrame: 4 days (Days 0, 2, 7 & 14): 14 day span
measure: Haemoglobin density
timeFrame: 7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span
measure: Methmoglobin density
timeFrame: 7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span
measure: Aspartate transaminase (AST)/alanine transaminase (ALT) ratio
timeFrame: 7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span
measure: Blood creatinine level
timeFrame: 7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span
measure: Asexual/sexual stage parasite density
timeFrame: 7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span
measure: Asexual/sexual stage parasite prevalence
timeFrame: 7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span
measure: Asexual/sexual stage parasite circulation time
timeFrame: 28 days
measure: Asexual/sexual stage parasite area under the curve (AUC)
timeFrame: 28 days
measure: Sexual stage parasite sex ratio
timeFrame: 7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span
measure: Incidence of adverse events
timeFrame: 7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span
Other outcomes:
Locations:
city: Bamako
country: Mali
facility: Malaria Research and Training Centre
Study officials:
affiliation: Malaria Research and Training Center, Bamako, Mali
name: Alassane Dicko, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stone W, Mahamar A, Smit MJ, Sanogo K, Sinaba Y, Niambele SM, Sacko A, Keita S, Dicko OM, Diallo M, Maguiraga SO, Samake S, Attaher O, Lanke K, Ter Heine R, Bradley J, McCall MBB, Issiaka D, Traore SF, Bousema T, Drakeley C, Dicko A. Single low-dose tafenoquine combined with dihydroartemisinin-piperaquine to reduce Plasmodium falciparum transmission in Ouelessebougou, Mali: a phase 2, single-blind, randomised clinical trial. Lancet Microbe. 2022 May;3(5):e336-e347. doi: 10.1016/S2666-5247(21)00356-6. Epub 2022 Mar 23.