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

Primary Purpose

Plasmodium Falciparum Infection

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ferroquine (SSR97193)
Placebo
artesunate
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Plasmodium Falciparum Infection

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Sanofi-Aventis Investigational Site Number 204001
  • Sanofi-Aventis Investigational Site Number 854002
  • Sanofi-Aventis Investigational Site Number 854003
  • Sanofi-Aventis Investigational Site Number 854001
  • Sanofi-Aventis Investigational Site Number 120001
  • Sanofi-Aventis Investigational Site Number 266001
  • Sanofi-Aventis Investigational Site Number 266002
  • Sanofi-Aventis Investigational Site Number 404001
  • Sanofi-Aventis Investigational Site Number 404002
  • Sanofi-Aventis Investigational Site Number 834001

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Ferroquine high dose + artesunate

Ferroquine medium dose + artesunate

Ferroquine low dose + artesunate

Ferroquine alone at medium dose

Arm 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.

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.

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.

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Cure rate at Day 28
Parasite Clearance Time (Median).
Fever Clearance Time (Median)
Recrudescent infections at Day 28 in the ferroquine group in monotherapy
Recrudescent infections at Day 63
Adequate Clinical and Parasitological Response (ACPR) at D28

Full Information

First Posted
October 1, 2009
Last Updated
June 27, 2011
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT00988507
Brief Title
Dose Ranging Study of Ferroquine With Artesunate in African Adults and Children With Uncomplicated Plasmodium Falciparum Malaria
Acronym
FARM
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
June 2011
Overall Recruitment Status
Terminated
Why Stopped
Company decision to modify the ferroquine development strategy; discontinuation not due to safety or activity unexpected findings
Study Start Date
October 2009 (undefined)
Primary Completion Date
November 2010 (Actual)
Study Completion Date
November 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Sanofi

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Plasmodium Falciparum Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
440 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ferroquine high dose + artesunate
Arm Type
Experimental
Arm 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.
Arm Title
Ferroquine medium dose + artesunate
Arm Type
Experimental
Arm 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.
Arm Title
Ferroquine low dose + artesunate
Arm Type
Experimental
Arm 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.
Arm Title
Ferroquine alone at medium dose
Arm Type
Experimental
Arm Description
Ferroquine at 4 mg/kg/d OD alone for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.
Intervention Type
Drug
Intervention Name(s)
Ferroquine (SSR97193)
Intervention Description
Pharmaceutical form: capsule Route of administration: oral
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Pharmaceutical form: capsule Route of administration: oral
Intervention Type
Drug
Intervention Name(s)
artesunate
Intervention Description
Pharmaceutical form: tablets Route of administration: oral
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Cure rate at Day 28
Time Frame
4 weeks
Title
Parasite Clearance Time (Median).
Time Frame
up to 63 days
Title
Fever Clearance Time (Median)
Time Frame
up to 63 days
Title
Recrudescent infections at Day 28 in the ferroquine group in monotherapy
Time Frame
4 weeks
Title
Recrudescent infections at Day 63
Time Frame
9 weeks
Title
Adequate Clinical and Parasitological Response (ACPR) at D28
Time Frame
4 weeks

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Sanofi-Aventis Investigational Site Number 204001
City
Cotonou
Country
Benin
Facility Name
Sanofi-Aventis Investigational Site Number 854002
City
Bobo-Dioulasso 01
Country
Burkina Faso
Facility Name
Sanofi-Aventis Investigational Site Number 854003
City
Nouna
Country
Burkina Faso
Facility Name
Sanofi-Aventis Investigational Site Number 854001
City
Ouagadougou
Country
Burkina Faso
Facility Name
Sanofi-Aventis Investigational Site Number 120001
City
Yaounde
Country
Cameroon
Facility Name
Sanofi-Aventis Investigational Site Number 266001
City
B.P. 118 Lambarene
Country
Gabon
Facility Name
Sanofi-Aventis Investigational Site Number 266002
City
Libreville
Country
Gabon
Facility Name
Sanofi-Aventis Investigational Site Number 404001
City
Kilifi
Country
Kenya
Facility Name
Sanofi-Aventis Investigational Site Number 404002
City
Kisumu
Country
Kenya
Facility Name
Sanofi-Aventis Investigational Site Number 834001
City
Korogwe
Country
Tanzania

12. IPD Sharing Statement

Citations:
PubMed Identifier
26342427
Citation
Held J, Supan C, Salazar CL, Tinto H, Bonkian LN, Nahum A, Moulero B, Sie 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, Mordmuller 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.
Results Reference
derived

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

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