Gametocytocidal and Transmission-blocking Efficacy of PQ in Combination With AL and TQ in Combination With SPAQ in Mali (NECTAR3)

London School of Hygiene and Tropical Medicine

Status and phase: Completed; Phase 2

Conditions: Malaria,Falciparum

Treatments: Drug: Artemether-lumefantrine; Drug: Tafenoquine; Drug: Sulphadoxine-pyrimethamine with amodiaquine; Drug: Primaquine Phosphate

Study type: Interventional

Funder types: Other

Identifiers

NCT05081089

26257

Details and patient eligibility

About

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.

Full description

Full protocol available on request.

Enrollment: 80 patients

Sex: All

Ages: 10 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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80 participants in 4 patient groups

Artemether-lumefantrine (AL)

Active Comparator group

Description:

Subjects will receive artemether-lumefantrine (AL) twice daily for 3 days.

Treatment:

Drug: Artemether-lumefantrine

AL with 0.25mg/kg primaquine (PQ)

Experimental group

Description:

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.

Treatment:

Drug: Primaquine Phosphate

Drug: Artemether-lumefantrine

Sulphadoxine-pyrimethamine with amodiaquine (SPAQ)

Active Comparator group

Description:

Subjects will receive sulphadoxine-pyrimethamine with amodiaquine (SPAQ) once daily for 3 days.

Treatment:

Drug: Sulphadoxine-pyrimethamine with amodiaquine

SPAQ with 1.66mg/kg tafenoquine (TQ)

Experimental group

Description:

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.

Treatment:

Drug: Sulphadoxine-pyrimethamine with amodiaquine

Drug: Tafenoquine