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

NCT ID: NCT04609098

Last Updated: 2022-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-29
• Study Completion Date: 2020-12-23

Brief Summary

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.

Detailed Description

Full protocol available on request.

Conditions

Malaria, Falciparum

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Dihydroartemisinin-Piperaquine (DP)

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.

Group Type: ACTIVE_COMPARATOR

Dihydroartemisinin/Piperaquine

Intervention Type: DRUG

Tablets containing 40 mg dihydroartemisinin/320 mg piperaquine (Eurartesim, Sigma Tau), administered according to weight as per the manufacturer instructions.

DP with 0.415mg/kg Tafenoquine (TQ)

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.

Group Type: EXPERIMENTAL

Tafenoquine 100mg [Arakoda]

Intervention Type: DRUG

Extemporaneous preparation of 1mg/mL Tafenoquine solution, from tablets containing 100mg primaquine (Arakoda, 60degrees pharmaceuticals, DC) dissolved in 100mL water with a non-interacting fruit-flavoured syrup. Solution will be given according to weight as indicated per treatment arm in 5kg bands.

Dihydroartemisinin/Piperaquine

Intervention Type: DRUG

Tablets containing 40 mg dihydroartemisinin/320 mg piperaquine (Eurartesim, Sigma Tau), administered according to weight as per the manufacturer instructions.

DP with 0.83 mg/kg TQ

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.

Group Type: EXPERIMENTAL

Tafenoquine 100mg [Arakoda]

Intervention Type: DRUG

Extemporaneous preparation of 1mg/mL Tafenoquine solution, from tablets containing 100mg primaquine (Arakoda, 60degrees pharmaceuticals, DC) dissolved in 100mL water with a non-interacting fruit-flavoured syrup. Solution will be given according to weight as indicated per treatment arm in 5kg bands.

Dihydroartemisinin/Piperaquine

Intervention Type: DRUG

Tablets containing 40 mg dihydroartemisinin/320 mg piperaquine (Eurartesim, Sigma Tau), administered according to weight as per the manufacturer instructions.

DP with 1.66mg/kg TQ

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.

Group Type: EXPERIMENTAL

Tafenoquine 100mg [Arakoda]

Intervention Type: DRUG

Extemporaneous preparation of 1mg/mL Tafenoquine solution, from tablets containing 100mg primaquine (Arakoda, 60degrees pharmaceuticals, DC) dissolved in 100mL water with a non-interacting fruit-flavoured syrup. Solution will be given according to weight as indicated per treatment arm in 5kg bands.

Dihydroartemisinin/Piperaquine

Intervention Type: DRUG

Tablets containing 40 mg dihydroartemisinin/320 mg piperaquine (Eurartesim, Sigma Tau), administered according to weight as per the manufacturer instructions.

Interventions

Tafenoquine 100mg [Arakoda]

Extemporaneous preparation of 1mg/mL Tafenoquine solution, from tablets containing 100mg primaquine (Arakoda, 60degrees pharmaceuticals, DC) dissolved in 100mL water with a non-interacting fruit-flavoured syrup. Solution will be given according to weight as indicated per treatment arm in 5kg bands.

Intervention Type: DRUG

Dihydroartemisinin/Piperaquine

Tablets containing 40 mg dihydroartemisinin/320 mg piperaquine (Eurartesim, Sigma Tau), administered according to weight as per the manufacturer instructions.

Intervention Type: DRUG

Other Intervention Names

Euartesim; Arakoda

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alassane Dicko, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Malaria Research and Training Center, Bamako, Mali

Locations

Malaria Research and Training Centre

Bamako, , Mali

Countries

Mali

References

Stone W, Mahamar A, Smit MJ, Sanogo K, Sinaba Y, Niambele SM, Sacko A, Keita S, Dicko OM, Diallo M, Maguiraga SO, Samake S, Attaher O, Lanke K, Ter Heine R, Bradley J, McCall MBB, Issiaka D, Traore SF, Bousema T, Drakeley C, Dicko A. Single low-dose tafenoquine combined with dihydroartemisinin-piperaquine to reduce Plasmodium falciparum transmission in Ouelessebougou, Mali: a phase 2, single-blind, randomised clinical trial. Lancet Microbe. 2022 May;3(5):e336-e347. doi: 10.1016/S2666-5247(21)00356-6. Epub 2022 Mar 23.

Reference Type: DERIVED

PMID: 35544095 (View on PubMed)

Related Links

http://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(21)00356-6/fulltext

Trial report

Other Identifiers

21905

Identifier Type: -

Identifier Source: org_study_id