Anti-parasitic Activity and Safety Assessment of SAR97276A in Children With Uncomplicated Malaria

Study Overview
=================
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

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

Conditions
-----------------
Malaria

Intervention / Treatment
-----------------
* Drug: SAR97276A
* Drug: arthemeter + lumefantrine (ACTs)


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Step 1 (SAR97276A od)<br>1 group of paediatric patients will receive 0.5 mg/kg SAR97276A administration once daily (od) for 3 days | Drug: SAR97276A<br>* Pharmaceutical form:solution for injection Route of administration: intramuscular<br>|
| Experimental: Step 1 (SAR97276A bid)<br>1 group of paediatric patients will receive 0.25 mg/kg SAR97276A administration twice daily (bid) for 3 days | Drug: SAR97276A<br>* Pharmaceutical form:solution for injection Route of administration: intramuscular<br>|
| Active Comparator: Step 1 (ACTs)<br>1 group of paediatric patients will receive arthemeter + lumefantrine (ACTs) bid for 3 days | Drug: arthemeter + lumefantrine (ACTs)<br>* Pharmaceutical form:tablet Route of administration: oral<br>|
| Experimental: Step 2 (SAR97276A)<br>1 or 2 groups of paediatric patients will receive SAR97276A once daily (od) or twice a day (bid) administration for 3 days (the choice of the od or bid regimen will be based on the results obtained in step 1) | Drug: SAR97276A<br>* Pharmaceutical form:solution for injection Route of administration: intramuscular<br>|
| Active Comparator: Step 2 (ACTs)<br>1 group of paediatric patients will receive arthemeter + lumefantrine (ACTs) bid for 3 days | Drug: arthemeter + lumefantrine (ACTs)<br>* Pharmaceutical form:tablet Route of administration: oral<br>|
| Experimental: Step 3 (SAR97276A)<br>1 group of paediatric patients (2 to 11 years old) will receive: SAR97276A od or bid administration for 3 days (depending on results of step 1) | Drug: SAR97276A<br>* Pharmaceutical form:solution for injection Route of administration: intramuscular<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parasite Reduction Ratio (PRR) |  | at 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of mean Parasitaemia over time (nb/µL) |  | every 6 hours from baseline up to 72 hours (day 4) | 
| Evolution of mean Gametocytes count over time (nb/µL) |  | from baseline to end of study (day 28 ± 2) | 
| Fever Clearance (time to reach Temperature < 38°C) |  | every 6 hours from baseline up to 72 hours (day 4) | 
| General conditions improvement: mean total symptom score over time |  | every 6 hours from baseline up to 72 hours (day 4) | 
| SAR97276 pharmacokinetic profile in plasma and blood |  | from baseline up to 12 hours after the last study drug intake on (Day 3 |