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

NCT05081089 | Completed Phase 2 DMC

• 1 other identifier: 26257
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria,Falciparum

Outcome Measures

Primary Outcomes (1)

• Change in mosquito infection rate assessed through membrane feeding assays (day 2 and day 7)

  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 Outcomes (15)

• Change in mosquito infection rate assessed through membrane feeding assays (all timepoints)

  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

  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

  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

  7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span

• Gametocyte infectivity

  7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span

Other Outcomes (4)

• Parasite genomic and transcriptomic variation assessed in RNA

  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

  7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span

• Human genomic variation analysis and association with parasite measure

  day 0

Study Arms (4)

Artemether-lumefantrine (AL)

ACTIVE COMPARATOR

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

Drug: Artemether-lumefantrine

AL with 0.25mg/kg primaquine (PQ)

EXPERIMENTAL

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: Artemether-lumefantrine; Drug: Primaquine Phosphate

Sulphadoxine-pyrimethamine with amodiaquine (SPAQ)

ACTIVE COMPARATOR

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

Drug: Sulphadoxine-pyrimethamine with amodiaquine

SPAQ with 1.66mg/kg tafenoquine (TQ)

EXPERIMENTAL

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; Drug: Tafenoquine

Interventions

Artemether-lumefantrine DRUG

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

Also known as: Riamet

AL with 0.25mg/kg primaquine (PQ); Artemether-lumefantrine (AL)

Primaquine Phosphate 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.

Also known as: Primaquine

AL with 0.25mg/kg primaquine (PQ)

Sulphadoxine-pyrimethamine with amodiaquine 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.

Also known as: Supyra

SPAQ with 1.66mg/kg tafenoquine (TQ); Sulphadoxine-pyrimethamine with amodiaquine (SPAQ)

Tafenoquine 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.

Also known as: Arakoda

SPAQ with 1.66mg/kg tafenoquine (TQ)

Eligibility Criteria

• Age: 10 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead

Study Sites (1)

Malaria Research and Training Centre

Bamako, Mali

Location

Related Publications (1)

• 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.

  PMID: 38705163 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Artemether, Lumefantrine Drug Combination; Primaquine; fanasil, pyrimethamine drug combination; Amodiaquine; tafenoquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Alassane Dicko

  Malaria Research and Training Centre, 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: September 13, 2021
• First Posted: October 18, 2021
• Study Start: October 12, 2021
• Primary Completion: December 16, 2021
• Study Completion: January 13, 2022
• Last Updated: January 18, 2022

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1)