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AzTrials

Malaria,FalciparumPhase 2NECTAR3NCT05081089

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

A Phase 2 study testing Artemether-lumefantrine, Primaquine Phosphate and Sulphadoxine-pyrimethamine with amodiaquine in people with Malaria,Falciparum, run by London School of Hygiene and Tropical Medicine at 1 site in Mali.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 10 to 50 yearsHealthy volunteers can take part
Conditions the study is for
Malaria,Falciparum
What is being tested?
Artemether-lumefantrine, Primaquine Phosphate and Sulphadoxine-pyrimethamine with amodiaquine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
1 siteMali
Study dates
12 Oct 2021to 13 Jan 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 10 to 50 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult

Who may be able to join

  • 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
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  • Individuals weighing < = 80 kg
  • No evidence of acute severe or chronic disease
  • Written, informed consent

Who cannot join

  • 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)
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  • 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 locations and contacts

1 site in 1 country.

Mali1 site

  • Malaria Research and Training Centre

    Bamako

Other trials in Mali

About this study

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

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.

Read the detailed description

Full protocol available on request.

Being tested
Artemether-lumefantrine, Primaquine Phosphate, Sulphadoxine-pyrimethamine with amodiaquine, Tafenoquine
Medical subject headings
Malaria, Falciparum

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Artemether-lumefantrineDrug

    Also called Riamet

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

  • Primaquine PhosphateDrug

    Also called Primaquine

    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.

  • Sulphadoxine-pyrimethamine with amodiaquineDrug

    Also called Supyra

    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.

  • TafenoquineDrug

    Also called Arakoda

    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.

Study groups in NCT05081089
Study groupRoleWhat they receive
Artemether-lumefantrine (AL)Active comparatorSubjects will receive artemether-lumefantrine (AL) twice daily for 3 days.
Receives: Drug: Artemether-lumefantrine
AL with 0.25mg/kg primaquine (PQ)ExperimentalSubjects 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.
Receives: Drug: Artemether-lumefantrine; Drug: Primaquine Phosphate
Sulphadoxine-pyrimethamine with amodiaquine (SPAQ)Active comparatorSubjects will receive sulphadoxine-pyrimethamine with amodiaquine (SPAQ) once daily for 3 days.
Receives: Drug: Sulphadoxine-pyrimethamine with amodiaquine
SPAQ with 1.66mg/kg tafenoquine (TQ)ExperimentalSubjects 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.
Receives: Drug: Sulphadoxine-pyrimethamine with amodiaquine; Drug: Tafenoquine

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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.

    Measured: 3 days (days 0, 2 and 7): 7 day span

Secondary outcomes (15)

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

    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.

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

  2. Mosquito infection rate assessed through membrane feeding assays

    Mosquito infection rate at all feeding time-points, with comparison within treatment arms compared to baseline, and between arms.

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

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

    Infectivity to mosquitoes at all feeding time-points, with comparison within treatment arms compared to baseline, and between arms.

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

  4. Mosquito infection density assessed through membrane feeding assays

    Oocyst intensity (in all/all infected mosquitoes) at all feeding time-points, with comparison within treatment arms compared to baseline, and between arms.

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

  5. Gametocyte infectivity

    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.

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

  6. Asexual/sexual stage parasite prevalence

    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.

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

  7. Asexual/sexual stage parasite density

    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.

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

  8. Sexual stage parasite sex ratio

    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.

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

  9. Sexual stage parasite circulation time

    Gametocyte circulation time (cumulative), determined by microscopy or molecular assays, compared within and between treatment arms.

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

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

    Gametocyte area under the curve (cumulative), determined by microscopy or molecular assays, compared within and between treatment arms.

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

  11. Haemoglobin density

    Haemoglobin density (g/dL) at all time-points, with comparison within treatment arms compared to baseline, and between arms.

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

  12. Change in haemoglobin density

    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.

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

  13. Methaemoglobin density

    Methaemoglobin density (g/dL) at all time-points, with comparison within treatment arms compared to baseline, and between arms.

    Measured: 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28)

  14. Change in methaemoglobin density

    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.

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

  15. Incidence of adverse events

    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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Oct 2021
  2. Study start12 Oct 2021
  3. Primary completion16 Dec 2021
  4. Study completion13 Jan 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05081089
Sponsor's protocol ID
26257
Acronym
NECTAR3
Status last verified
Aug 2021
First submitted
13 Sep 2021
Last updated
18 Jan 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Anonymised individual participant data may be shared on a digital repository or upon reasonable request.

Publications

  • Mahamar A, Smit MJ, Sanogo K, Sinaba Y, Niambele SM, Sacko A, Dicko OM, Diallo M, Maguiraga SO, Sankare Y, Keita S, Samake S, Dembele A, Lanke K, Ter Heine R, Bradley J, Dicko Y, Traore SF, Drakeley C, Dicko A, Bousema T, Stone W. Artemether-lumefantrine with or without single-dose primaquine and sulfadoxine-pyrimethamine plus amodiaquine with or without single-dose tafenoquine to reduce Plasmodium falciparum transmission: a phase 2, single-blind, randomised clinical trial in Ouelessebougou, Mali. Lancet Microbe. 2024 Jul;5(7):633-644. doi: 10.1016/S2666-5247(24)00023-5. Epub 2024 May 2.

    PubMed 38705163

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Artemether-lumefantrine, Primaquine Phosphate and Sulphadoxine-pyrimethamine with amodiaquine in people with Malaria,Falciparum, run by London School of Hygiene and Tropical Medicine at 1 site in Mali.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Mali. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05081089, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2022.

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