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

NCT00988507 | Terminated Phase 2 DMC

• 1 other identifier: DRI10382
• Study Type: interventional
• Target: 440
• Locations: 6 countries
• Sites: 10

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.

Conditions

Plasmodium Falciparum Infection

Outcome Measures

Primary Outcomes (1)

• 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

  4 weeks

Secondary Outcomes (6)

• Cure rate at Day 28

  4 weeks

• Parasite Clearance Time (Median).

  up to 63 days

• Fever Clearance Time (Median)

  up to 63 days

• Recrudescent infections at Day 28 in the ferroquine group in monotherapy

  4 weeks

• Recrudescent infections at Day 63

  9 weeks

Study Arms (4)

Ferroquine high dose + artesunate

EXPERIMENTAL

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.

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

Ferroquine medium dose + artesunate

EXPERIMENTAL

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.

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

Ferroquine low dose + artesunate

EXPERIMENTAL

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.

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

Ferroquine alone at medium dose

EXPERIMENTAL

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

Drug: Ferroquine (SSR97193); Drug: Placebo

Interventions

Ferroquine (SSR97193) DRUG

Pharmaceutical form: capsule Route of administration: oral

Ferroquine alone at medium dose; Ferroquine high dose + artesunate; Ferroquine low dose + artesunate; Ferroquine medium dose + artesunate

Placebo DRUG

Pharmaceutical form: capsule Route of administration: oral

Ferroquine alone at medium dose; Ferroquine high dose + artesunate; Ferroquine low dose + artesunate; Ferroquine medium dose + artesunate

artesunate DRUG

Pharmaceutical form: tablets Route of administration: oral

Ferroquine high dose + artesunate; Ferroquine low dose + artesunate; Ferroquine medium dose + artesunate

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (10)

Sanofi-Aventis Investigational Site Number 204001

Cotonou, Benin

Location

Sanofi-Aventis Investigational Site Number 854002

Bobo-Dioulasso, Burkina Faso

Location

Sanofi-Aventis Investigational Site Number 854003

Nouna, Burkina Faso

Location

Sanofi-Aventis Investigational Site Number 854001

Ouagadougou, Burkina Faso

Location

Sanofi-Aventis Investigational Site Number 120001

Yaoundé, Cameroon

Location

Sanofi-Aventis Investigational Site Number 266001

B.P. 118 Lambarene, Gabon

Location

Sanofi-Aventis Investigational Site Number 266002

Libreville, Gabon

Location

Sanofi-Aventis Investigational Site Number 404001

Kilifi, Kenya

Location

Sanofi-Aventis Investigational Site Number 404002

Kisumu, Kenya

Location

Sanofi-Aventis Investigational Site Number 834001

Korogwe, Tanzania

Location

Related Publications (1)

• 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.

  PMID: 26342427 DERIVED

MeSH Terms

Interventions

ferroquine; Artesunate

Intervention Hierarchy (Ancestors)

Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 1, 2009
• First Posted: October 2, 2009
• Study Start: October 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: June 28, 2011

Record last verified: 2011-06

Locations

GA (2); BE (1); TA (1); KE (2); CA (1); BU (3)