Dose Ranging Study of Ferroquine With Artesunate in African Adults and Children With Uncomplicated Plasmodium Falciparum Malaria (FARM)

Sanofi

Status and phase: Terminated; Phase 2

Conditions: Plasmodium Falciparum Infection

Treatments: Drug: Ferroquine (SSR97193); Drug: artesunate; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00988507

DRI10382

Details and patient eligibility

About

Primary objective: To assess the Day 28 efficacy defined as the percentage of patients with no parasitic recrudescence, of 3 treatment groups - 3 dose levels of ferroquine associated with artesunate - for a 3-day treatment.

Secondary objectives:

• To assess the efficacy of ferroquine at one dose level alone for a 3-day treatment.
• To assess the clinical safety of 4 treatment groups - 3 dose levels of ferroquine associated with artesunate and one dose level of ferroquine alone.
• To assess pharmacokinetics parameters of ferroquine and its metabolites along sparse sampling schedules.

Full description

The overall study duration is 64 days, consisting of a screening period (less or equal 1 day), of a 3-day treatment period during which the patient is hospitalized for a maximum of 60 hours, and a follow-up period of 61 days.

Enrollment: 440 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• 3 cohorts enrolled in sequence with data interim review by Data Monitoring Committee (DMC) between cohort 1-2 and cohort 2-3

  • Cohort 1 : Adults > 50 kg or Adolescents >30 kg and age > or = 14 years
  • Cohort 2 : Children with body weight [30 kg- 15 kg[
  • Cohort 3 : Children with body weight [15 kg-10 kg]

• Age related Body Mass Index (BMI)> or = 5 th percentile.

• Presence of body temperature > or = 37.5°C or history of fever in the last 24 hours.

• Monoinfection with Plasmodium falciparum with parasitemia from 1,000/microL to 200,000/microL.

• Signed Informed Consent Form by the patient (if the patient is > or = age defining majority) or by the parents or legal guardian of minor patients (<18 years of age or < other age locally defining majority). In addition, participants with capacity for writing will sign off on an Assent Form. Patients with no capacity for writing will have the Assent Form read. In that case, an impartial witness will certify the document was read to the child.

Exclusion criteria

• Presence of HBs antigen and of anti-HCV antibodies

• Laboratory parameters with clinical significant abnormalities and/or reaching critical values : Hemoglobin (< 7g/dl), hematocrit, red blood cell count, white blood cell, reticulocytes, platelets, glucose, creatinine, aspartate transferase (AST), alanine transferase (ALT > 3 ULN), alkaline phosphatase, total bilirubine > 1.5 ULN.

• History or presence of any clinically significant disease or symptoms which might confound the interpretation of the safety and efficacy information.

• Splenectomized patients.

• Presence of criteria for complicated malaria

• Patients unable to drink

• Breastfeeding patients.

• Permanent vomiting.

• Female participants with child bearing potential not willing to use an effective contraceptive(s) method(s) for the duration of the study (e.g. implants, oral contraceptives, some intra-uterine devices or a double barrier method). The need for an efficient method will be reminded to the patient and the patient's legal guardian(s) by the investigator.

• Previous treatment within 5 times the elimination half-life or within the last 14 days, whichever the longest :

  • with any anti-malaria agents i.e., quinine, chloroquine, amodiaquine, mefloquine, halofantrine, sufladoxine-pyrimethamine, doxycycline-pyrimethamine, primaquine, artemether, atovaquone, proguanil, lumefantrine,
  • with an other investigational drug
  • with 2D6 main substrates

• Past or concomitant participation in a study with an anti-malaria vaccine.

• Measles vaccine injection within the last 15 days.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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440 participants in 4 patient groups

Ferroquine high dose + artesunate

Experimental group

Description:

Ferroquine at 6 mg/kg/d OD and artesunate 4mg/kg/d OD for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.

Treatment:

Drug: Placebo

Drug: artesunate

Drug: Ferroquine (SSR97193)

Ferroquine medium dose + artesunate

Experimental group

Description:

Ferroquine at 4 mg/kg/d OD and artesunate 4mg/kg/d OD for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.

Treatment:

Drug: Placebo

Drug: artesunate

Drug: Ferroquine (SSR97193)

Ferroquine low dose + artesunate

Experimental group

Description:

Ferroquine at 2 mg/kg/d OD and artesunate 4mg/kg/d OD for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.

Treatment:

Drug: Placebo

Drug: artesunate

Drug: Ferroquine (SSR97193)

Ferroquine alone at medium dose

Experimental group

Description:

Ferroquine at 4 mg/kg/d OD alone for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.

Treatment:

Drug: Placebo

Drug: Ferroquine (SSR97193)