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

NCT ID: NCT05081089

Last Updated: 2022-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-12
• Study Completion Date: 2022-01-13

Brief 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). 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.

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

Artemether-lumefantrine (AL)

Subjects will receive artemether-lumefantrine (AL) twice daily for 3 days.

Group Type: ACTIVE_COMPARATOR

Artemether-lumefantrine

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Artemether-lumefantrine

Intervention Type: DRUG

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

Primaquine Phosphate

Intervention Type: DRUG

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 amodiaquine (SPAQ)

Subjects will receive sulphadoxine-pyrimethamine with amodiaquine (SPAQ) once daily for 3 days.

Group Type: ACTIVE_COMPARATOR

Sulphadoxine-pyrimethamine with amodiaquine

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Sulphadoxine-pyrimethamine with amodiaquine

Intervention Type: DRUG

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.

Tafenoquine

Intervention Type: DRUG

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.

Interventions

Artemether-lumefantrine

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

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Riamet; Primaquine; Supyra; Arakoda

Eligibility Criteria

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

• Minimum Eligible Age: 10 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

Role: PRINCIPAL_INVESTIGATOR

Malaria Research and Training Centre, Mali

Locations

Malaria Research and Training Centre

Bamako, , Mali

Countries

Mali

References

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.

Reference Type: DERIVED

PMID: 38705163 (View on PubMed)

Other Identifiers

26257

Identifier Type: -

Identifier Source: org_study_id