Study to Investigate the Clinical and Parasiticidal Activity and Pharmacokinetics of Different Doses of Artefenomel and Ferroquine in Patients With Uncomplicated Plasmodium Falciparum Malaria
Condition: Plasmodium Falciparum Infection
MeSH terms: Malaria; Malaria, Falciparum
Intervention: Artefenomel (OZ439); Ferroquine (SSR97193)
Intervention description: Pharmaceutical form: Granules for oral suspension Route of administration: Oral; Pharmaceutical form: Capsule Route of administration: Oral
Intervention MeSH terms: Artefenomel; Ferroquine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 140.0
Sex: All
Minimum age: 14 Years
Maximum age: 69 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To show the contribution of artefenomel (OZ439) to the clinical and parasiticidal effect of
      OZ439/Ferroquine (FQ) combination by analyzing exposure-response of OZ439 measured by Day 28
      polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response
      (ACPR) for the effect and the area under the curve (AUC) of OZ439 as pharmacokinetic (PK)
      predictor.

      Secondary Objectives:

        -  To evaluate the exposure-response of OZ439 combined with FQ on crude Day 28 ACPR.

        -  To evaluate the dose response of OZ439 combined with FQ on PCR-corrected and crude Day
           28 ACPR.

        -  To evaluate the dose-response of OZ439 combined with FQ on selected secondary endpoints.

        -  To evaluate the safety and tolerability of different dosages of OZ439 in combination
           with FQ and FQ alone.

        -  To characterize the PK of OZ439 in plasma, and of FQ and its active metabolite SSR97213
           in blood.
    

Eligibility criteria:

        Inclusion criteria :

        Participants (14-69 years old inclusive) with body weight within 35 and 90 kilograms (kg),
        with uncomplicated Plasmodium falciparum (P. falciparum) malaria, with a fever as defined
        with axillary temperature greater than or equal to (>=) 37.5 degree Celsius (°C) or oral/
        rectal/ tympanic temperature >=38°C or history of fever in the previous 24 hours (history
        of fever was documented), with a mono-infection with P. falciparum and parasitemia
        (microscopically, blood smear) >= 3,000 and less than or equal to (<=) 50,000 asexual
        parasites per microliter of blood.

        Exclusion criteria:

          -  Presence of severe malaria.

          -  Known history or evidence of clinically significant gastrointestinal, cardiovascular,
             hepatic, renal, hematological, respiratory, endocrine, immunological, infectious,
             neurological (in particular convulsions), malignancy, psychiatric disease or symptoms
             which, in the judgment of the investigator, might confuse the interpretation of the
             safety information.

          -  Severe vomiting defined as more than 3 times in the 24 hours prior to enrollment in
             the study or inability to tolerate oral treatment or severe diarrhea defined as 3 or
             more watery stools per day.

          -  Severe malnutrition defined as a body mass index of less than 16 kg per meter square
             for adults and for children Z-score less than (<) -3 or weight for age (%) of the
             median <60.

          -  Splenectomized participants or presence of surgical scar on left hypochondrium.

          -  Known history of hypersensitivity, allergic, or anaphylactoid reactions to FQ or other
             amino quinolines or to OZ439 or OZ277 or any of the excipients.

          -  Participant treated with anti-malarial treatment:

          -  With piperaquine phosphate-based compound, mefloquine, naphthoquine or
             sulphadoxine/pyrimethamine within the previous 6 weeks.

          -  With amodiaquine or chloroquine within the previous 4 weeks.

          -  With quinine, halofantrine, lumefantrine-based compounds and any other anti-malarial
             treatment or antibiotics with antimalarial activity (including cotrimoxazole,
             tetracyclines, quinolones and fluoroquinolones, and azithromycin) within the past 14
             days.

          -  With any herbal products or traditional medicines, within the past 7 days.

          -  Previous treatment within 5 times the half-life or within the last 14 days, whichever
             the longest, which were: strong Cytochrome P450 (CYP) 2C or CYP3A inhibitors and/or
             moderate inhibitors but inhibiting both CYP2C and CYP3A and/or CYP inducers.

          -  Any treatment known to induce a prolongation of QT interval.

          -  Participated in any trial investigating OZ439 and/or FQ compounds.

          -  Previous participation in any malaria vaccine study or received malaria vaccine in any
             other circumstance.

          -  Enrolled in another clinical trial within the past 4 weeks or during the study period.

          -  Mixed Plasmodium infection.

          -  Presence of Hepatitis A - immunoglobulin, Hepatitis B surface antigen or Hepatitis C
             virus antibody and/or known to had active Hepatitis C virus ribonucleic acid.

          -  Laboratory parameters with abnormalities deemed clinically significant by the
             investigator.

          -  Abnormal Liver Function Test: aspartate transferase greater than (>) 2 upper limit of
             normal range (ULN), or alanine transferase >2 ULN or total bilirubin >1.5 ULN.

          -  Positive pregnancy test at study screening for female participants of childbearing
             potential.

          -  QT interval corrected using Fridericia formula (QTcF) >450 milliseconds at screening
             or pre-dose.

          -  Hypokalemia (<3.5 millimoles per liter [mmol/L]), hypocalcemia (<2.0 mmol/L) or
             hypomagnesemia (<0.5 mmol/L) at screening or pre-dose.

          -  Family history of sudden death or of congenital prolongation of the QT interval or
             known congenital prolongation of the QT-interval or any clinical condition known to
             prolong the QT interval e.g., participants with a history of symptomatic cardiac
             arrhythmias including atrial fibrillation or with clinically relevant bradycardia.

          -  Participant not suitable for participation, whatever the reason, as judged by the
             Investigator, included medical or clinical conditions, or participants potentially at
             risk of noncompliance to study procedures or unable to drink.

        The above information was not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.