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

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

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

Study Overview

• Status: Terminated
• Conditions: Malaria
• Intervention / Treatment: Drug: SAR97276A; Drug: arthemeter + lumefantrine (ACTs)

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Benin
  • Cotonou, Benin
    • Investigational Site Number 204001
• Burkina Faso
  • Ouagadougou, Burkina Faso
    • Investigational Site Number 854001
• Gabon
  • Libreville, Gabon
    • Investigational Site Number 266001
• Kenya
  • Kisumu, Kenya
    • Investigational Site Number 404001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Step 1 (SAR97276A od); 1 group of paediatric patients will receive 0.5 mg/kg SAR97276A administration once daily (od) for 3 days	Drug: SAR97276A; Pharmaceutical form:solution for injection Route of administration: intramuscular
Experimental: Step 1 (SAR97276A bid); 1 group of paediatric patients will receive 0.25 mg/kg SAR97276A administration twice daily (bid) for 3 days	Drug: SAR97276A; Pharmaceutical form:solution for injection Route of administration: intramuscular
Active Comparator: Step 1 (ACTs); 1 group of paediatric patients will receive arthemeter + lumefantrine (ACTs) bid for 3 days	Drug: arthemeter + lumefantrine (ACTs); Pharmaceutical form:tablet Route of administration: oral
Experimental: Step 2 (SAR97276A); 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; Pharmaceutical form:solution for injection Route of administration: intramuscular
Active Comparator: Step 2 (ACTs); 1 group of paediatric patients will receive arthemeter + lumefantrine (ACTs) bid for 3 days	Drug: arthemeter + lumefantrine (ACTs); Pharmaceutical form:tablet Route of administration: oral
Experimental: Step 3 (SAR97276A); 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; Pharmaceutical form:solution for injection Route of administration: intramuscular

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: September 26, 2011
• First Submitted That Met QC Criteria: September 30, 2011
• First Posted (Estimate): October 4, 2011

Study Record Updates

• Last Update Posted (Estimate): December 13, 2012
• Last Update Submitted That Met QC Criteria: December 12, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Lumefantrine
• Other Study ID Numbers: PDY11737; 2010-021398-36 (EudraCT Number); U1111-1118-0694 (Other Identifier: UTN)