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

January 14, 2022 updated by: London School of Hygiene and Tropical Medicine

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Full protocol available on request.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mali
      • Bamako, Mali
        • Malaria Research and Training Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

10 years to 50 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Artemether-lumefantrine (AL)
Subjects will receive artemether-lumefantrine (AL) twice daily for 3 days.
Drug: Artemether-lumefantrine
Tablets containing 20/80 mg artemether and 120/480 mg lumefantrine will be administered according to weight as per manufacturer guidelines.
Other Names:
  • Riamet
Experimental: AL with 0.25mg/kg primaquine (PQ)
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.
Drug: Primaquine Phosphate
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
Drug: Artemether-lumefantrine
Tablets containing 20/80 mg artemether and 120/480 mg lumefantrine will be administered according to weight as per manufacturer guidelines.
Other Names:
  • Riamet
Active Comparator: Sulphadoxine-pyrimethamine with amodiaquine (SPAQ)
Subjects will receive sulphadoxine-pyrimethamine with amodiaquine (SPAQ) once daily for 3 days.
Drug: Sulphadoxine-pyrimethamine with amodiaquine
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
Experimental: SPAQ with 1.66mg/kg tafenoquine (TQ)
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.
Drug: Sulphadoxine-pyrimethamine with amodiaquine
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
Drug: Tafenoquine
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
3 days (days 0, 2 and 7): 7 day span

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
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.
7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
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.
7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
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.
7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
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.
7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
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 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
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.
7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
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.
7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
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.
7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
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.
7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
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.
8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
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.
8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
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.
8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28)
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.
8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
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.
8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Human genomic variation analysis and association with parasite measure
Time Frame: day 0
Human genotype analysis at baseline (G6PD, CYP2D6, and HBB type)
day 0
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.
7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
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.
7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span
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.
8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
London School of Hygiene and Tropical Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 12, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 16, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 13, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 13, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 4, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 18, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 18, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 14, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 26257

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Anonymised individual participant data may be shared on a digital repository or upon reasonable request.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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