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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00988507
Recruitment Status : Terminated (Company decision to modify the ferroquine development strategy; discontinuation not due to safety or activity unexpected findings)
First Posted : October 2, 2009
Last Update Posted : June 28, 2011
Sponsor:
Information provided by:
Sanofi

Tracking Information
First Submitted Date  ICMJE October 1, 2009
First Posted Date  ICMJE October 2, 2009
Last Update Posted Date June 28, 2011
Study Start Date  ICMJE October 2009
Actual Primary Completion Date November 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 1, 2009)
Recrudescent infections at D28 in the groups with ferroquine associated with artesunate. Recrudescence is defined as the recurrence of the same original strain of Plasmodium falciparum regardless of clinical symptoms [ Time Frame: 4 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00988507 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2009)
  • Cure rate at Day 28 [ Time Frame: 4 weeks ]
  • Parasite Clearance Time (Median). [ Time Frame: up to 63 days ]
  • Fever Clearance Time (Median) [ Time Frame: up to 63 days ]
  • Recrudescent infections at Day 28 in the ferroquine group in monotherapy [ Time Frame: 4 weeks ]
  • Recrudescent infections at Day 63 [ Time Frame: 9 weeks ]
  • Adequate Clinical and Parasitological Response (ACPR) at D28 [ Time Frame: 4 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose Ranging Study of Ferroquine With Artesunate in African Adults and Children With Uncomplicated Plasmodium Falciparum Malaria
Official Title  ICMJE Parallel Group, Double-blind, Randomized Study Assessing the Efficacy, Safety and Pharmacokinetic Profiles of Ferroquine Associated With Artesunate and a Single-blind Dose Level of Ferroquine Alone in a 3-day Treatment of Uncomplicated Malaria Due to Plasmodium Falciparum in an Immune Symptomatic African Adult and Pediatric Population.
Brief Summary

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.
Detailed 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Plasmodium Falciparum Infection
Intervention  ICMJE
  • Drug: Ferroquine (SSR97193)

    Pharmaceutical form: capsule

    Route of administration: oral

  • Drug: Placebo

    Pharmaceutical form: capsule

    Route of administration: oral

  • Drug: artesunate

    Pharmaceutical form: tablets

    Route of administration: oral

Study Arms  ICMJE
  • Experimental: Ferroquine high dose + artesunate
    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.
    Interventions:
    • Drug: Ferroquine (SSR97193)
    • Drug: Placebo
    • Drug: artesunate
  • Experimental: Ferroquine medium dose + artesunate
    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.
    Interventions:
    • Drug: Ferroquine (SSR97193)
    • Drug: Placebo
    • Drug: artesunate
  • Experimental: Ferroquine low dose + artesunate
    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.
    Interventions:
    • Drug: Ferroquine (SSR97193)
    • Drug: Placebo
    • Drug: artesunate
  • Experimental: Ferroquine alone at medium dose
    Ferroquine at 4 mg/kg/d OD alone for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.
    Interventions:
    • Drug: Ferroquine (SSR97193)
    • Drug: Placebo
Publications * Held J, Supan C, Salazar CL, Tinto H, Bonkian LN, Nahum A, Moulero B, Sié A, Coulibaly B, Sirima SB, Siribie M, Otsyula N, Otieno L, Abdallah AM, Kimutai R, Bouyou-Akotet M, Kombila M, Koiwai K, Cantalloube C, Din-Bell C, Djeriou E, Waitumbi J, Mordmüller B, Ter-Minassian D, Lell B, Kremsner PG. Ferroquine and artesunate in African adults and children with Plasmodium falciparum malaria: a phase 2, multicentre, randomised, double-blind, dose-ranging, non-inferiority study. Lancet Infect Dis. 2015 Dec;15(12):1409-19. doi: 10.1016/S1473-3099(15)00079-1. Epub 2015 Sep 3.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Estimated Enrollment  ICMJE
 (submitted: October 1, 2009)
440
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2010
Actual Primary Completion Date November 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Gabon,   Benin,   Burkina Faso,   Cameroon,   Kenya,   Tanzania
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00988507
Other Study ID Numbers  ICMJE DRI10382
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Trial Transparency Team, sanofi-aventis
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP