CALINA: 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

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04300309
Collaborator
European and Developing Countries Clinical Trials Partnership (EDCTP) (Other), Medicines for Malaria Venture (MMV), Switzerland (Other), Groupe de Recherche Action en Santé (GRAS), Ouagadougou, Burkina Faso (Other), Institut de Recherche en sciences de la Santé - Unité de Recherche Clinique de Nanoro (IRSS-URCN), Burkina Faso (Other)
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Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
  • Drug: artemether:lumefantrine (2.5 mg:30 mg)
Phase 2/Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
44 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Dec 21, 2020
Anticipated Primary Completion Date :
Jul 10, 2023
Anticipated Study Completion Date :
May 27, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: artemether lumefantrine (2.5 mg:30 mg)

artemether lumefantrine (2.5 mg:30 mg) bid over 3 days, from 1-4 tablets per dose

Drug: artemether:lumefantrine (2.5 mg:30 mg)
artemether:lumefantrine (2.5 mg:30 mg)
Other Names:
  • bid over 3 days, from 1-4 tablets per dose
  • Outcome Measures

    Primary Outcome Measures

    1. Artemether Cmax [Day 1]

      ART Cmax (represents the higher concentration between the concentrations at 1 hour and 2 hours after first dose)

    Secondary Outcome Measures

    1. Lumefantrine Day 8 concentration (C168h) [168h post first dose]

    2. Artemether AUC [Up to Day 15 post first dose]

    3. DHA AUC [Up to Day 15 post first dose]

    4. Lumefantrine Cmax [Up to Day 8 post first dose]

    5. Lumefantrine AUC [Up to Day 15 post first dose]

      derived as appropriate

    6. Parasite Clearance Time (PCT) [Up to Day 8]

      Parasite count will be performed by microscopy

    7. Fever clearance Times (FCT) [Up to Day 8]

      Body temperature will be recorded

    8. PCR-corrected Adequate Clinical and Parasitological Response (ACPR) [Day 15]

      PCR-corrected Adequate Clinical and Parasitological Response (ACPR) at Day 15

    9. PCR-corrected Adequate Clinical and Parasitological Response (ACPR) [Day 43]

      PCR-corrected Adequate Clinical and Parasitological Response (ACPR) at Day 43

    10. PCR-corrected Adequate Clinical and Parasitological Response (ACPR) [Day 29]

      PCR-corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29

    11. Uncorrected Adequate Clinical and Parasitological Response (ACPR) [Day 8]

      Uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 8

    12. Uncorrected Adequate Clinical and Parasitological Response (ACPR) [Day 15]

      Uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 15

    13. Uncorrected Adequate Clinical and Parasitological Response (ACPR) [Day 29]

      Uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 29

    14. Uncorrected Adequate Clinical and Parasitological Response (ACPR) [Day 43]

      Uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 43

    15. Incidence rate of recrudescence and new infections [Up to Day 43]

      Incidence rate of recrudescence and new infections at Days 15, 29 and 43

    16. Incidence rate of serious adverse events [during the study period from Baseline up to age 365 days]

      safety by collecting serious adverse events (SAEs)

    17. Incidence rate of adverse events [during the study period from Baseline up to day 43]

      safety and tolerability by collecting adverse events (AEs)

    18. Incidence rate of abnormal laboratory values [during the study period from Baseline up to day 43]

      Safety and tolerability by collecting routine safety laboratory assessments

    19. Change in head circumference [at Baseline and at age 365 days]

      Head circumference will be measured

    20. Neurodevelopmental assessment [At Day 4 and at age 365 days]

      Neurodevelopmental assessment (Shoklo Malaria Research Unit assessment) score will be derived

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 365 Days
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    1. 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)

    2. 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)

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

    2. Patients unable to swallow or whose drinking is impaired

    3. 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

    4. 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

    5. 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

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

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

    8. 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)

    9. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Nanoro Burkina Faso
    2 Novartis Investigative Site Ouagadougou Burkina Faso
    3 Novartis Investigative Site Kisantu Bas Kongo Congo, The Democratic Republic of the
    4 Novartis Investigative Site Sotuba Mali

    Sponsors and Collaborators

    • Novartis Pharmaceuticals
    • European and Developing Countries Clinical Trials Partnership (EDCTP)
    • Medicines for Malaria Venture (MMV), Switzerland
    • 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

    Investigators

    • Principal Investigator: Alfred Tiono, Groupement de Recherche Action en Santé (GRAS), Ouagadougou, Burkina Faso
    • Principal Investigator: Halidou Tinto, Unité de Recherche Clinique, CMA St Camille, Nanoro, Burkina Faso
    • Principal Investigator: Bernhards Ogutu, Kondele Children Hospital, Kisumu , Kenya
    • Principal Investigator: Issaka Sagara, MRTC, Univ. of Science, Techniques and Technology, Bamako, Mali
    • Principal Investigator: Martin Meremikwu, Department of Paediatrics, University of Calabar, Calabar, Nigeria
    • Principal Investigator: Gildas Wounounou, Hôpital Général de Référence St Luc, Kisantu, DR Congo
    • Principal Investigator: Christine Manyando, St Pauls Mission Hospital, Nchelenge, Zambia

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT04300309
    Other Study ID Numbers:
    • CCOA566B2307
    First Posted:
    Mar 9, 2020
    Last Update Posted:
    May 6, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 6, 2022