Gametocytocidal and Transmission-blocking Efficacy of ASAQ and ALAQ With or Without PQ in Mali

NCT05550909 | Completed Phase 2 DMC

• 1 other identifier: 28041
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the gametocytocidal and transmission reducing activity of artesunate-amodiaquine (ASAQ) and artemether-lumefantrine-amodiaquine (ALAQ) with and without a single dose of 0.25mg/kg primaquine (PQ). Outcome measures will include infectivity to mosquitoes at 2, 7 and 14 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

  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 ASAQ, ASAQ-PQ, AL, ALAQ and ALAQ-PQ arms.

  2 days (days 0 and 2): 3 day span

Secondary Outcomes (13)

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

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

• Mosquito infection rate assessed through membrane feeding assays

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

• Human infectivity to locally reared mosquitoes assessed through membrane feeding assays

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

• Mosquito infection density assessed through membrane feeding assays

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

• Gametocyte infectivity

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

Other Outcomes (5)

• Parasite genomic and transcriptomic variation assessed in RNA

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

• The impact of plasma biomarkers on malaria transmission efficiency

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

• Human genomic variation analysis and association with parasite measure

  day 0

Study Arms (5)

artesunate-amodiaquine (ASAQ)

ACTIVE COMPARATOR

Subjects will receive artesunate-amodiaquine (ASAQ) daily for 3 days.

Drug: Artesunate-amodiaquine combination

ASAQ with 0.25mg/kg primaquine (PQ)

EXPERIMENTAL

Subjects will receive artesunate-amodiaquine (ASAQ) daily for 3 days and a single dose of 0.25mg/kg primaquine (PQ) on the first day of ASAQ treatment.

Drug: Artesunate-amodiaquine combination; Drug: Primaquine Phosphate

Artemether-Lumefantrine (AL)

ACTIVE COMPARATOR

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

Drug: Artemether-lumefantrine

Artemether-Lumefantrine-Amodiaquine (ALAQ)

EXPERIMENTAL

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

Drug: Artemether-lumefantrine; Drug: Amodiaquine

Artemether-Lumefantrine-Amodiaquine (ALAQ) with 0.25 mg/kg primaquine (PQ)

EXPERIMENTAL

Subjects will receive artemether-lumefantrine (AL) and amodiaquine (AQ) twice daily for 3 days and a single dose of 0.25mg/kg primaquine (PQ) on the first day of ALAQ treatment.

Drug: Primaquine Phosphate; Drug: Artemether-lumefantrine; Drug: Amodiaquine

Interventions

Artesunate-amodiaquine combination DRUG

Tablets containing 50mg/135 mg or 100mg/270 mg of artesunate/amodiaquine will be administered according to weight as per manufacturer guidelines

Also known as: Camoquin

ASAQ with 0.25mg/kg primaquine (PQ); artesunate-amodiaquine (ASAQ)

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

ASAQ with 0.25mg/kg primaquine (PQ); Artemether-Lumefantrine-Amodiaquine (ALAQ) with 0.25 mg/kg primaquine (PQ)

Artemether-lumefantrine DRUG

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

Also known as: Coartem

Artemether-Lumefantrine (AL); Artemether-Lumefantrine-Amodiaquine (ALAQ); Artemether-Lumefantrine-Amodiaquine (ALAQ) with 0.25 mg/kg primaquine (PQ)

Amodiaquine DRUG

Tablets containing 153 mg of amodiaquine will be administered according to weight, aiming for a dosage of approximately 10 mg (7.7-15.3mg)/kg/day, given once or twice daily (together with artemether-lumefantrine) for three days.

Artemether-Lumefantrine-Amodiaquine (ALAQ); Artemether-Lumefantrine-Amodiaquine (ALAQ) with 0.25 mg/kg primaquine (PQ)

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
• 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
• Haemoglobin ≥ 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, such as sudden high fevers, shaking or severe sore throat or ulcers in the mouth during treatment with Amodiaquine
• Current eye disease with retinal damage
• Signs of severe malaria, including hyperparasitaemia (defined as asexual parasitaemia \> 100,000 parasites / µL)
• Signs of acute or chronic illness, including hepatitis
• The use of other medication (except for paracetamol and/or aspirin), including antacids, other medicines used to treat malaria, abnormal heart rhythm, depression or mental illness or HIV/AIDS, and medicines that have antibiotic/antifungal properties
• 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 or HIV/AIDS, malignancy or conditions that may affect absorption of study medication e.g., severe diarrhoea 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.
• Known Electrocardiogram (ECG) corrected QT interval of more than 450 ms
• Documented or self-reported history of cardiac conduction problems
• Documented or self-reported history of epileptic seizures

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, Vanheer LN, Smit MJ, Sanogo K, Sinaba Y, Niambele SM, Diallo M, Dicko OM, Diarra RS, Maguiraga SO, Youssouf A, Sacko A, Keita S, Samake S, Dembele A, Teelen K, Dicko Y, Traore SF, Dondorp A, Drakeley C, Stone W, Dicko A. Artemether-lumefantrine-amodiaquine or artesunate-amodiaquine combined with single low-dose primaquine to reduce Plasmodium falciparum malaria transmission in Ouelessebougou, Mali: a five-arm, phase 2, single-blind, randomised controlled trial. Lancet Microbe. 2025 Feb;6(2):100966. doi: 10.1016/j.lanmic.2024.100966. Epub 2024 Dec 17.

  PMID: 39701119 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

amodiaquine, artesunate drug combination; Amodiaquine; Primaquine; Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; 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

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 15, 2022
• First Posted: September 22, 2022
• Study Start: October 17, 2022
• Primary Completion: December 30, 2022
• Study Completion: January 26, 2023
• Last Updated: October 1, 2024

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1)