Evaluation of Artesunate in Infants Being Treated for Severe Malaria

Pharmacokinetic Evaluation of Artesunate in Infants Being Treated for Severe Malaria - Research Laboratory Addendum to the Observational Study Titled: Safety and Efficacy of Artesunate in Pregnant Women and Infants (< One Month of Age)

This is essentially a laboratory study that is an addendum to an ongoing prospective Phase 4 multicenter observational study titled: "Safety and Efficacy of Artesunate in Pregnant Women and Infants (ARTEMUM)" being conducted in France. Infants, the parents of whom provided consent to have data collected from their child as part of the ARTEMUM study, will have an additional blood sample collected when other standard of care blood specimens are collected during the 2-day period after the start of intravenous (IV) artesunate treatment. A maximum of 4 samples will be taken and plasma will be isolated and stored frozen until analysis for plasma artesunate and dihydroartemisinin (DHA) concentrations. Red blood cells will also be frozen for further analysis (for example Kelch-13 mutations). In addition, a standard of care blood sample will be collected approximately one month post treatment for clinical laboratory tests.

Study Overview

• Status: Recruiting
• Conditions: Malaria
• Intervention / Treatment: Drug: Artesunate Injection

Detailed Description

This is essentially a laboratory study that is an addendum to an ongoing prospective Phase 4 multicenter observational study titled: "Safety and Efficacy of Artesunate in Pregnant Women and Infants (ARTEMUM)" being conducted in France. Parents of infants under 2 years of age who provided consent to participate in the ARTEMUM study will be asked to provide consent for their child to this laboratory study providing the infant was eligible for the ARTEMUM study. During the first 48 hours after the start of IV artesunate treatment, a maximum of 4 samples of blood will be collected when other standard of care samples are being collected. With regard to blood collected for standard of care, it is recognized that samples between 0.25 and 5 hours post doses will be the most useful for pharmacokinetic (PK) analysis due to the 30-to-45-minute half-life of DHA. Plasma will be isolated and frozen until submission to the central laboratory for artesunate and DHA plasma concentrations. In addition, a standard of care blood sample will be collected approximately one month post treatment for clinical laboratory tests. The recommendation by the World Health Organization (WHO) is followed in France not only for safety (anemia) but also for relapse. Clinical laboratory test results and other data to be included in the analysis will be abstracted from the case report forms (CRFs) from the ARTEMUM study.

• Study Type: Observational
• Enrollment (Estimated): 15

Contacts and Locations

• Study Contact: Name: Bernadette Tock; Phone Number: 2404018634; Email: btock@fasttrackresearch.com

Study Locations

• France
  • Paris, France, 75014
    • Recruiting
    • Hôpital Cochin Port Royal
    • Contact: Caroline Charlier-Woerther; Phone Number: 01 58 41 41 11; Email: caroline.charlier@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Infants < 2 years of age with malaria (positive blood by PCR or thin or thick smear or RDT treated with at least 1 dose of intravenous artesunate with hemoglobin (Hb) levels ≥ 7.0 g/dL.

Description

Inclusion Criteria:

• Parental consent provided to the ARTEMUM Study
• Parental consent provided to participate in this PK Laboratory Study
• Infants < 2 years of age with malaria (positive blood by polymerase chain reaction (PCR) or thin or thick smear or rapid diagnostic test (RDT), or any combination of those) treated by at least 1 dose of intravenous artesunate

Exclusion Criteria:

• Hemoglobin < 7.0 g/dL at the time when additional blood sample for PK assessment will be drawn as part of standard of care

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in concentration of artesunate in blood plasma samples	Change in concentration of artesunate in blood plasma samples collected as part of standard of care	Approximately at 5 minutes, 30 minutes, 90 minutes, and 4 hours after artesunate intravenous injection
Change in concentration of dihydroartemisinin in blood plasma samples	Change in concentration of dihydroartemisinin in blood plasma samples collected as part of standard of care	Approximately at 5 minutes, 30 minutes, 90 minutes, and 4 hours after artesunate intravenous injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety, as measured by the number of participants with adverse events	Safety, as measured by the number of participants with adverse events	During standard of care treatment with intravenous artesunate
Tolerability, as measured by the number of doses of artesunate administered to each participant	Tolerability of artesunate treatment, as measured by the number of doses of artesunate administered to each participant	During standard of care treatment with intravenous artesunate

Collaborators and Investigators

• Sponsor: Amivas (US), LLC
• Investigators: Principal Investigator: Bryan Smith, MD, Amivas, Inc

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2024
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): February 28, 2030

Study Registration Dates

• First Submitted: August 13, 2024
• First Submitted That Met QC Criteria: August 13, 2024
• First Posted (Actual): August 15, 2024

Study Record Updates

• Last Update Posted (Estimated): December 10, 2024
• Last Update Submitted That Met QC Criteria: December 5, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Infant; Artesunate
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; Protozoan Infections; Parasitic Diseases; Malaria; Anti-Infective Agents; Antineoplastic Agents; Antiviral Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Artesunate
• Other Study ID Numbers: IVAS-PEDS-PK-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No