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

NCT04609098 | Completed Phase 2 DMC

• 1 other identifier: 21905
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria, Falciparum

Outcome Measures

Primary Outcomes (1)

• Change in mosquito infectivity assessed through membrane feeding assays (day 7)

  The proportion of mosquitoes infected, assessed through membrane feeding and measured as oocyst prevalence in mosquitoes dissected on day 7 post feed, compared to baseline

  2 days (Days 0 & 7): 7 day span

Secondary Outcomes (14)

• Change in mosquito infectivity assessed through membrane feeding assays (days 2 and 14)

  3 days (Days 0, 2, & 14): 14 day span

• Mosquito infection density assessed through membrane feeding assays

  4 days (Days 0, 2, 7 & 14): 14 day span

• Mosquito infection prevalence assessed through membrane feeding assays

  4 days (Days 0, 2, 7 & 14): 14 day span

• Human infectivity assessed through membrane feeding assays

  4 days (Days 0, 2, 7 & 14): 14 day span

• Haemoglobin density

  7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span

Study Arms (4)

Dihydroartemisinin-Piperaquine (DP)

ACTIVE COMPARATOR

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.

Drug: Dihydroartemisinin/Piperaquine

DP with 0.415mg/kg Tafenoquine (TQ)

EXPERIMENTAL

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.

Drug: Dihydroartemisinin/Piperaquine; Drug: Tafenoquine 100mg [Arakoda]

DP with 0.83 mg/kg TQ

EXPERIMENTAL

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.

Drug: Dihydroartemisinin/Piperaquine; Drug: Tafenoquine 100mg [Arakoda]

DP with 1.66mg/kg TQ

EXPERIMENTAL

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.

Drug: Dihydroartemisinin/Piperaquine; Drug: Tafenoquine 100mg [Arakoda]

Interventions

Dihydroartemisinin/Piperaquine DRUG

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

Also known as: Euartesim

DP with 0.415mg/kg Tafenoquine (TQ); DP with 0.83 mg/kg TQ; DP with 1.66mg/kg TQ; Dihydroartemisinin-Piperaquine (DP)

Tafenoquine 100mg [Arakoda] 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.

Also known as: Arakoda

DP with 0.415mg/kg Tafenoquine (TQ); DP with 0.83 mg/kg TQ; DP with 1.66mg/kg TQ

Eligibility Criteria

• Age: 12 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead

Study Sites (1)

Malaria Research and Training Centre

Bamako, Mali

Location

Related Publications (1)

• 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.

  PMID: 35544095 DERIVED

Related Links

• Trial report

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

artenimol; piperaquine; tafenoquine

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Alassane Dicko, PhD, MD

  Malaria Research and Training Center, Bamako, Mali

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: This is a single blind randomised controlled trial. The treating physician and staff involved with assessing all laboratory outcomes of the study are blinded, but no placebo will be used. The study pharmacist will be unblinded and responsible for randomisation and treatment administration.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2020
• First Posted: October 30, 2020
• Study Start: October 29, 2020
• Primary Completion: December 2, 2020
• Study Completion: December 23, 2020
• Last Updated: June 9, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1)