Skip to main content
OpenTrials
Completed

NCT Number: NCT05081089

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Malaria,Falciparum Infections Malaria Malaria, Falciparum Mosquito-Borne Diseases Parasitic Diseases Protozoan Infections Vector Borne Diseases

Age range

10 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Malaria Research and Training Centre

Bamako, Mali

About this study

Full protocol available on request.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Artemether-lumefantrine

Drug

Tablets containing 20/80 mg artemether and 120/480 mg lumefantrine will be administered according to weight as per manufacturer guidelines.

Other names: Riamet

Primaquine Phosphate

Drug

The single dose of 0.25mg/kg PQ will be administered in an aqueous solution, according to a standard operating procedure (SOP) provided by the manufacturer.

Other names: Primaquine

Sulphadoxine-pyrimethamine with amodiaquine

Drug

Sulfadoxine/pyrimethamine tablets contain 500mg sulfadoxine and 25mg pyrimethamine. Amodiaquine tablets contain 150mg amodiaquine (as hydrochloride). Tablets will be administered according to weight as per manufacturer guidelines.

Other names: Supyra

Tafenoquine

Drug

100mg tafenoquine tablets are prepared into a 1mg/mL solution in water. Solution will be given according to weight as indicated per treatment arm in 5kg bands.

Other names: Arakoda

Primary outcomes

  1. Change in mosquito infection rate assessed through membrane feeding assays (day 2 and day 7)

    Time frame: 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 outcomes

  1. Change in mosquito infection rate assessed through membrane feeding assays (all timepoints)

    Time frame: 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.

  2. Mosquito infection rate assessed through membrane feeding assays

    Time frame: 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.

  3. Human infectivity to locally reared mosquitoes assessed through membrane feeding assays

    Time frame: 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.

  4. Mosquito infection density assessed through membrane feeding assays

    Time frame: 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.

  5. Gametocyte infectivity

    Time frame: 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.

  6. Asexual/sexual stage parasite prevalence

    Time frame: 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.

  7. Asexual/sexual stage parasite density

    Time frame: 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.

  8. Sexual stage parasite sex ratio

    Time frame: 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.

  9. Sexual stage parasite circulation time

    Time frame: 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.

  10. Sexual stage parasite area under the curve (AUC)

    Time frame: 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.

  11. Haemoglobin density

    Time frame: 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.

  12. Change in haemoglobin density

    Time frame: 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.

  13. Methaemoglobin density

    Time frame: 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.

  14. Change in methaemoglobin density

    Time frame: 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.

  15. Incidence of adverse events

    Time frame: 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.

Other outcomes

  1. Parasite genomic and transcriptomic variation assessed in RNA

    Time frame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span

    Parasite genotype and transcriptional analysis at baseline and at post-treatment timepoints.

  2. The impact of plasma biomarkers on malaria transmission efficiency

    Time frame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span

    Plasma biomarkers (antibodies and parasite protein) at baseline and at post-treatment timepoints.

  3. Human genomic variation analysis and association with parasite measure

    Time frame: day 0

    Human genotype analysis at baseline (G6PD, CYP2D6, and HBB type)

  4. ALT/AST/Creatine density

    Time frame: 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span

    ALT/AST/Creatine density at all time-points with comparison within treatment arms compared to baseline, and between arms.

Sponsors and collaborators

Lead sponsor

London School of Hygiene and Tropical Medicine

Other

Registry information

Official study 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

Acronym: NECTAR3

Important dates

Study start
2021
Primary completion
2021
Study completion
2022
First posted
Oct 18, 2021
Registry last updated
Jan 18, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.