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

NCT ID: NCT00988507

Last Updated: 2011-06-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 440 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2010-11-30

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.

Conditions

Plasmodium Falciparum Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Ferroquine (SSR97193)

Intervention Type: DRUG

Pharmaceutical form: capsule

Route of administration: oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: capsule

Route of administration: oral

artesunate

Intervention Type: DRUG

Pharmaceutical form: tablets

Route of administration: oral

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.

Group Type: EXPERIMENTAL

Ferroquine (SSR97193)

Intervention Type: DRUG

Pharmaceutical form: capsule

Route of administration: oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: capsule

Route of administration: oral

artesunate

Intervention Type: DRUG

Pharmaceutical form: tablets

Route of administration: oral

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.

Group Type: EXPERIMENTAL

Ferroquine (SSR97193)

Intervention Type: DRUG

Pharmaceutical form: capsule

Route of administration: oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: capsule

Route of administration: oral

artesunate

Intervention Type: DRUG

Pharmaceutical form: tablets

Route of administration: oral

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.

Group Type: EXPERIMENTAL

Ferroquine (SSR97193)

Intervention Type: DRUG

Pharmaceutical form: capsule

Route of administration: oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: capsule

Route of administration: oral

Interventions

Ferroquine (SSR97193)

Pharmaceutical form: capsule

Route of administration: oral

Intervention Type: DRUG

Placebo

Pharmaceutical form: capsule

Route of administration: oral

Intervention Type: DRUG

artesunate

Pharmaceutical form: tablets

Route of administration: oral

Intervention Type: DRUG

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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

sanofi-aventis

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Sanofi-Aventis Investigational Site Number 204001

Cotonou, , Benin

Sanofi-Aventis Investigational Site Number 854002

Bobo-Dioulasso, , Burkina Faso

Sanofi-Aventis Investigational Site Number 854003

Nouna, , Burkina Faso

Sanofi-Aventis Investigational Site Number 854001

Ouagadougou, , Burkina Faso

Sanofi-Aventis Investigational Site Number 120001

Yaoundé, , Cameroon

Sanofi-Aventis Investigational Site Number 266001

B.P. 118 Lambarene, , Gabon

Sanofi-Aventis Investigational Site Number 266002

Libreville, , Gabon

Sanofi-Aventis Investigational Site Number 404001

Kilifi, , Kenya

Sanofi-Aventis Investigational Site Number 404002

Kisumu, , Kenya

Sanofi-Aventis Investigational Site Number 834001

Korogwe, , Tanzania

Countries

Benin; Burkina Faso; Cameroon; Gabon; Kenya; Tanzania

References

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.

Reference Type: DERIVED

PMID: 26342427 (View on PubMed)

Other Identifiers

DRI10382

Identifier Type: -

Identifier Source: org_study_id