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

Malaria, Falciparum Clinical Trial

— NECTAR2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04609098
• Other study ID #: 21905
• Status: Completed
• Phase: Phase 2
• Start date: October 29, 2020
• Est. completion date: December 23, 2020

Study information

• Verified date: June 2022
• Source: London School of Hygiene and Tropical Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Full protocol available on request.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: December 23, 2020
• Est. primary completion date: December 2, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Malaria, Falciparum

Intervention

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

Locations

Country	Name	City	State
Mali	Malaria Research and Training Centre	Bamako

Sponsors (1)

Lead Sponsor	Collaborator
London School of Hygiene and Tropical Medicine

Country where clinical trial is conducted

Mali, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in mosquito infectivity assessed through membrane feeding assays (days 2 and 14)	The proportion of mosquitoes infected, assessed through membrane feeding and measured as oocyst prevalence in mosquitoes dissected on day 2 and 14 post feed, compared to baseline	3 days (Days 0, 2, & 14): 14 day span
Secondary	Mosquito infection density assessed through membrane feeding assays	Mosquito infection density, assessed through membrane feeding and measured as oocyst density in mosquitoes dissected on day 2, 7 and 14 post feed, compared within and between study arms	4 days (Days 0, 2, 7 & 14): 14 day span
Secondary	Mosquito infection prevalence assessed through membrane feeding assays	Mosquito infection prevalence and density, assessed through membrane feeding and measured as oocyst prevalence in mosquitoes dissected on day 2, 7 and 14 post feed, compared within and between study arms	4 days (Days 0, 2, 7 & 14): 14 day span
Secondary	Human infectivity assessed through membrane feeding assays	The proportion of individuals that infect any number of mosquitoes, assessed through membrane feeding and measured as oocyst prevalence/density in mosquitoes dissected on day 2, 7 and 14 post feed, compared within and between study arms	4 days (Days 0, 2, 7 & 14): 14 day span
Secondary	Haemoglobin density	Haemolysis will be monitored by measuring haemoglobin levels (g/dL) on days 0, 1, 2, 7, 14, 21, and 28 post treatment as part of the clinical assessment.	7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span
Secondary	Methmoglobin density	Methmoglobin density (g/dL) will be monitored on days 0, 1, 2, 7, 14, 21, and 28 post treatment as part of the clinical assessment.	7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span
Secondary	Aspartate transaminase (AST)/alanine transaminase (ALT) ratio	Aspartate transaminase (AST)/alanine transaminase (ALT) ratio will be recorded on days 0, 1, 2, 7, 14, 21, and 28 post treatment as part of the clinical assessment.	7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span
Secondary	Blood creatinine level	Blood creatine level will be recorded on days 0, 1, 2, 7, 14, 21, and 28 post treatment as part of the clinical assessment.	7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span
Secondary	Asexual/sexual stage parasite density	Asexual/sexual stage parasite density (parasites/microlitre) will be measured by microscopy and by molecular methods on days 0, 1, 2, 7, 14, 21, and 28 post treatment.	7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span
Secondary	Asexual/sexual stage parasite prevalence	Asexual/sexual stage parasite prevalence will be measured by microscopy and by molecular methods on days 0, 1, 2, 7, 14, 21, and 28 post treatment.	7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span
Secondary	Asexual/sexual stage parasite circulation time	Asexual/sexual stage parasite circulation time (days) will be determined from measures of density.	28 days
Secondary	Asexual/sexual stage parasite area under the curve (AUC)	Asexual/sexual stage parasite area under the curve (AUC: Gametocytes per microlitre per day) will be determined from measures of density.	28 days
Secondary	Sexual stage parasite sex ratio	Gametocyte density will be determined by molecular methods for males and females separately, allowing analysis of sex ratio (proportion of total that is male) on days 0, 1, 2, 7, 14, 21 and 28 post treatment.	7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span
Secondary	Incidence of adverse events	Incidence of adverse events will be monitored at each active (day 0,1,2,7,14,21,28) follow up visit. AE's will also be recorded and acted upon if present at any other time during follow up.	7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span