Pharmacokinetics, Safety, Tolerability and Efficacy of a New Artemether-lumefantrine Dispersible Tablet in Infants and Neonates <5 kg Body Weight With Acute Uncomplicated Plasmodium Falciparum Malaria

Plasmodium Falciparum Malaria Clinical Trial

— CALINA  

Official title:

Multicenter, Open-label, Single-arm Study to Evaluate the PK, Safety, Tolerability and Efficacy of a New Artemether:Lumefantrine (2.5 mg:30 mg) Dispersible Tablet in the Treatment of Infants and Neonates <5 kg Body Weight With Acute Uncomplicated Plasmodium Falciparum Malaria

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04300309
• Other study ID #: CCOA566B2307
• Secondary ID: PACTR20200453545
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: December 21, 2020
• Est. completion date: June 10, 2024

Study information

• Verified date: February 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to evaluate PK, safety, tolerability and efficacy of a new formulation of artemether-lumefantrine dispersible tablet in neonates and infants <5 kg body weight with acute uncomplicated Plasmodium falciparum malaria.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 28
• Est. completion date: June 10, 2024
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 365 Days

Eligibility

Inclusion Criteria:

1. Male or female neonates/infants

2. Body weight <5 kg but = 2 kg

3. In Cohort 1, infants aged >28 days; in Cohort 2, neonates aged 1 to =28 days (3 subgroups: 1-7 days; 8-14 days; 15-28 days)

4. Microscopically confirmed diagnosis of P. falciparum malaria (or mixed infections):

• in Cohort 1 of =500 and <100,000 parasites/µL asexual P. falciparum parasitemia

• in Cohort 2 of =100 and <100,000 parasites/µL asexual P. falciparum parasitemia

• in Cohort 2, either congenital or neonatal

• either symptomatic or asymptomatic

Exclusion Criteria:

1. Head circumference < - 2 SD z-score in cm following WHO age and sex-specific reference curves (suspicion of microcephaly)

2. Presence of severe malaria (according to WHO 2015 definition)

3. HIV status :

• in Cohort 1, patient's or patient's mother's current treatment with ARV

• in Cohort 2, mother's known HIV positive status at patient's birth or mother's current treatment with ARV

4. Presence of the following signs of a critical condition: apnea-bradycardia, sustained bradycardia, tachycardia, desaturation, hypotension, hypothermia; or other severely deteriorated general condition (based on IMCI criteria in sick infants) (WHO 2005)

5. Presence of any clinically significant neurological condition:

• any episode of convulsion during the present illness (in keeping with the IMCI list of general danger signs)

• known neurological disorders (e.g. chronic seizure disorders, cerebral palsy)

6. Presence of clinically significant abnormality of the hepatic and renal systems

7. Patients unable to swallow or whose drinking is impaired

8. Known hypersensitivity of the patient or either patient's parent to artemether, lumefantrine, any of the excipients of Coartem®/Riamet® Dispersible tablet, or to drugs of similar chemical classes

9. History of malabsorption or previous gastrointestinal surgery, or history of radiation therapy that could affect drug absorption or metabolism, or any other disorder or history of a condition that could interfere with drug absorption, distribution, metabolism, or excretion

10. Known family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to be associated with prolongation of the QTc interval such as history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease

11. Disturbances of electrolyte balance (e.g. hypokalaemia or hypomagnesaemia)

12. Presence of any age-adjusted clinically or hematologically relevant laboratory and blood chemistry abnormalities

13. Patients who received any antimalarial drug, including antibiotics with antimalarial activity, within 14 days of trial start, or any other prohibited drug (see Table 6-2)

14. Patients who received an investigational drug within 5 half-lives of enrollment or participated in an investigational study or within 30 days, whichever is longer

Related Conditions & MeSH terms

• Body Weight
• Malaria
• Malaria, Falciparum
• Plasmodium Falciparum Malaria

Intervention

Drug:
• artemether:lumefantrine (2.5 mg:30 mg)
artemether:lumefantrine (2.5 mg:30 mg)

Locations

Country	Name	City	State
Burkina Faso	Novartis Investigative Site	Nanoro
Burkina Faso	Novartis Investigative Site	Ouagadougou
Congo, The Democratic Republic of the	Novartis Investigative Site	Kisantu	Bas Kongo

Sponsors (5)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	European and Developing Countries Clinical Trials Partnership (EDCTP), Groupe de Recherche Action en Santé (GRAS), Ouagadougou, Burkina Faso, Institut de Recherche en sciences de la Santé - Unité de Recherche Clinique de Nanoro (IRSS-URCN), Burkina Faso, Medicines for Malaria Venture (MMV), Switzerland

Countries where clinical trial is conducted

Burkina Faso,  Congo, The Democratic Republic of the, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Artemether Cmax	ART Cmax (represents the higher concentration between the concentrations at 1 hour and 2 hours after first dose)	Day 1
Secondary	Lumefantrine Day 8 concentration (C168h)		168h post first dose
Secondary	Artemether AUC		Up to Day 15 post first dose
Secondary	DHA AUC		Up to Day 15 post first dose
Secondary	Lumefantrine Cmax		Up to Day 8 post first dose
Secondary	Lumefantrine AUC	derived as appropriate	Up to Day 15 post first dose
Secondary	Parasite Clearance Time (PCT)	Parasite count will be performed by microscopy	Up to Day 8
Secondary	Fever clearance Times (FCT)	Body temperature will be recorded	Up to Day 8
Secondary	PCR-corrected Adequate Clinical and Parasitological Response (ACPR)	PCR-corrected Adequate Clinical and Parasitological Response (ACPR) at Day 15	Day 15
Secondary	PCR-corrected Adequate Clinical and Parasitological Response (ACPR)	PCR-corrected Adequate Clinical and Parasitological Response (ACPR) at Day 43	Day 43
Secondary	PCR-corrected Adequate Clinical and Parasitological Response (ACPR)	PCR-corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29	Day 29
Secondary	Uncorrected Adequate Clinical and Parasitological Response (ACPR)	Uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 8	Day 8
Secondary	Uncorrected Adequate Clinical and Parasitological Response (ACPR)	Uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 15	Day 15
Secondary	Uncorrected Adequate Clinical and Parasitological Response (ACPR)	Uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 29	Day 29
Secondary	Uncorrected Adequate Clinical and Parasitological Response (ACPR)	Uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 43	Day 43
Secondary	Incidence rate of recrudescence and new infections	Incidence rate of recrudescence and new infections at Days 15, 29 and 43	Up to Day 43
Secondary	Incidence rate of serious adverse events	safety by collecting serious adverse events (SAEs)	during the study period from Baseline up to age 365 days
Secondary	Incidence rate of adverse events	safety and tolerability by collecting adverse events (AEs)	during the study period from Baseline up to day 43
Secondary	Incidence rate of abnormal laboratory values	Safety and tolerability by collecting routine safety laboratory assessments	during the study period from Baseline up to day 43
Secondary	Change in head circumference	Head circumference will be measured	at Baseline and at age 365 days
Secondary	Neurodevelopmental assessment	Neurodevelopmental assessment (Shoklo Malaria Research Unit assessment) score will be derived	At Day 4 and at age 365 days