Clinical trial NCT01445938: Anti-parasitic Activity and Safety Assessment of SAR97276A in Children With Uncomplicated Malaria
Official title: An Open-label, Randomized Multicenter Study to Investigate the Anti-parasitic Activity, Pharmacokinetic and Safety of IM SAR97276A With Oral ACTs as Positive Control in Children Presenting With Symptomatic Plasmodium Falciparum Uncomplicated Malaria
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Malaria
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2011-10-04
Enrollment: 20
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To assess the antiparasitic activity of intramuscular (IM) SAR97276A based on parasite reduction ratio at 72 hours in pediatric patients with uncomplicated malaria

Secondary Objectives:

* To assess the evolution of clinical signs and symptoms (including the need for a rescue therapy) in pediatric patients with uncomplicated malaria receiving SAR97276A with reference to Artemisinin-Based Combination Therapy (ACTs)
* To assess the pharmacokinetics profile of SAR97276A in pediatric patients with uncomplicated malaria
* To assess the safety profile of SAR97276A in pediatric patients with uncomplicated malaria
* To assess the pharmacokinetic-pharmacodynamic relationship of SAR97276A

Detailed description: The total duration per patients will last approximately 28 ± 2 days broken down as follows:

* A screening phase up to 12-hours
* A 28 ± 2 days study period

Eligibility criteria: Inclusion criteria:

* Patients diagnosed with symptomatic infection by Plasmodium falciparum microscopically confirmed in blood smear at Day-1 visit
* Fever (tympanic or rectal temperature ≥ 38 C) or documented history of fever within the last 24h
* Asexual parasitemia of ≥ 2 000 parasites/μL in blood smear at D-1 visit
* Signed Informed Consent Form by the parents or legal guardian
* Age: 12 to 17 years old for step 1
* Age: 2 to 11 years old for step 2 and step 3

Exclusion criteria:

* Participation in another clinical trial within the last 3 months or participation within a different cohort in this PDY11737 clinical trial or participation to previous trial with SAR97276
* Documented history of adequate treatment with antimalarials expected to be effective within the preceding 72 hours
* Severe concomitant disease (including concomitant febrile illnesses or infection)
* Any sign suggestive of severe malaria
* Severe malnutrition
* Asexual parasitemia: Plasmodium falciparum \> 100,000 parasites/μL in blood smear at D-1 visit
* Previous treatment within 3 weeks prior to inclusion, and concomitant treatment with potent CYP3A4 inhibitors or CYP3A4 inducers or CYP2D6 substrates or potent CYP2D6 inhibitors
* Known serious adverse event reaction or hypersensitivity to Artemisinin-Based Combination Therapy (ACTs) or any contraindications from the positive control therapy (Artemisinin Combined Treatments) or warning/precaution of use as defined in the respective National Product Labeling
* Pregnant or breast-feeding women
* Women of childbearing potential not protected by effective contraceptive method of birth control, or not willing to use an effective contraceptive(s) method(s) for the duration of the study (e.g.: double barrier method), and/or who are unwilling or unable to be tested for pregnancy,
* CPK above 3 ULN,
* Underlying hepatobiliary disease or ALT\>3 ULN.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Parasite Reduction Ratio (PRR)
timeFrame: at 72 hours
Secondary outcomes:
measure: Evolution of mean Parasitaemia over time (nb/µL)
timeFrame: every 6 hours from baseline up to 72 hours (day 4)
measure: Evolution of mean Gametocytes count over time (nb/µL)
timeFrame: from baseline to end of study (day 28 ± 2)
measure: Fever Clearance (time to reach Temperature < 38°C)
timeFrame: every 6 hours from baseline up to 72 hours (day 4)
measure: General conditions improvement: mean total symptom score over time
timeFrame: every 6 hours from baseline up to 72 hours (day 4)
measure: SAR97276 pharmacokinetic profile in plasma and blood
timeFrame: from baseline up to 12 hours after the last study drug intake on (Day 3
Other outcomes:
Locations:
city: Cotonou
country: Benin
facility: Investigational Site Number 204001
city: Ouagadougou
country: Burkina Faso
facility: Investigational Site Number 854001
city: Libreville
country: Gabon
facility: Investigational Site Number 266001
city: Kisumu
country: Kenya
facility: Investigational Site Number 404001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Held J, Supan C, Salazar CLO, Tinto H, Bonkian LN, Nahum A, Sie A, Abdulla S, Cantalloube C, Djeriou E, Bouyou-Akotet M, Ogutu B, Mordmuller B, Kreidenweiss A, Siribie M, Sirima SB, Kremsner PG. Safety and efficacy of the choline analogue SAR97276 for malaria treatment: results of two phase 2, open-label, multicenter trials in African patients. Malar J. 2017 May 4;16(1):188. doi: 10.1186/s12936-017-1832-x.