Single Low Dose Tafenoquine to Reduce P. Falciparum Transmission in Mali (NECTAR2)

London School of Hygiene and Tropical Medicine

Status and phase: Completed; Phase 2

Conditions: Malaria, Falciparum

Treatments: Drug: Dihydroartemisinin/Piperaquine; Drug: Tafenoquine 100mg [Arakoda]

Study type: Interventional

Funder types: Other

Identifiers

NCT04609098

21905

Details and patient eligibility

About

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.

Full description

Full protocol available on request.

Enrollment: 80 patients

Sex: All

Ages: 12 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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80 participants in 4 patient groups

Dihydroartemisinin-Piperaquine (DP)

Active Comparator group

Description:

Subjects will receive Dihydroartemisinin-Piperaquine (DP) once daily for 3 days, and a low dose of 1.66mg/kg, 0.83mg/kg, or 0.415mg/kg. Tafenoquine (TQ) on the first date of DP treatment.

Treatment:

Drug: Dihydroartemisinin/Piperaquine

DP with 0.415mg/kg Tafenoquine (TQ)

Experimental group

Description:

Subjects will receive Dihydroartemisinin-Piperaquine (DP) once daily for 3 days, and a single dose of 0.415mg/kg Tafenoquine (TQ) on the first date of DP treatment.

Treatment:

Drug: Tafenoquine 100mg [Arakoda]

Drug: Dihydroartemisinin/Piperaquine

DP with 0.83 mg/kg TQ

Experimental group

Description:

Subjects will receive Dihydroartemisinin-Piperaquine (DP) once daily for 3 days, and a single dose of 0.83mg/kg Tafenoquine (TQ) on the first date of DP treatment.

Treatment:

Drug: Tafenoquine 100mg [Arakoda]

Drug: Dihydroartemisinin/Piperaquine

DP with 1.66mg/kg TQ

Experimental group

Description:

Subjects will receive Dihydroartemisinin-Piperaquine (DP) once daily for 3 days, and single dose of 1.66mg/kg Tafenoquine (TQ) on the first date of DP treatment.

Treatment:

Drug: Tafenoquine 100mg [Arakoda]

Drug: Dihydroartemisinin/Piperaquine