Clinical trial NCT00988507: Dose Ranging Study of Ferroquine With Artesunate in African Adults and Children With Uncomplicated Plasmodium Falciparum Malaria
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Plasmodium Falciparum Infection
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2009-10-02
Enrollment: 440
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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
timeFrame: 4 weeks
Secondary outcomes:
measure: Cure rate at Day 28
timeFrame: 4 weeks
measure: Parasite Clearance Time (Median).
timeFrame: up to 63 days
measure: Fever Clearance Time (Median)
timeFrame: up to 63 days
measure: Recrudescent infections at Day 28 in the ferroquine group in monotherapy
timeFrame: 4 weeks
measure: Recrudescent infections at Day 63
timeFrame: 9 weeks
measure: Adequate Clinical and Parasitological Response (ACPR) at D28
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Cotonou
country: Benin
facility: Sanofi-Aventis Investigational Site Number 204001
city: Bobo-Dioulasso 01
country: Burkina Faso
facility: Sanofi-Aventis Investigational Site Number 854002
city: Nouna
country: Burkina Faso
facility: Sanofi-Aventis Investigational Site Number 854003
city: Ouagadougou
country: Burkina Faso
facility: Sanofi-Aventis Investigational Site Number 854001
city: Yaounde
country: Cameroon
facility: Sanofi-Aventis Investigational Site Number 120001
city: B.P. 118 Lambarene
country: Gabon
facility: Sanofi-Aventis Investigational Site Number 266001
city: Libreville
country: Gabon
facility: Sanofi-Aventis Investigational Site Number 266002
city: Kilifi
country: Kenya
facility: Sanofi-Aventis Investigational Site Number 404001
city: Kisumu
country: Kenya
facility: Sanofi-Aventis Investigational Site Number 404002
city: Korogwe
country: Tanzania
facility: Sanofi-Aventis Investigational Site Number 834001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
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.