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

NCT ID: NCT01445938

Last Updated: 2012-12-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2012-01-31

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

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Step 1 (SAR97276A od)

1 group of paediatric patients will receive 0.5 mg/kg SAR97276A administration once daily (od) for 3 days

Group Type: EXPERIMENTAL

SAR97276A

Intervention Type: DRUG

Pharmaceutical form:solution for injection

Route of administration: intramuscular

Step 1 (SAR97276A bid)

1 group of paediatric patients will receive 0.25 mg/kg SAR97276A administration twice daily (bid) for 3 days

Group Type: EXPERIMENTAL

SAR97276A

Intervention Type: DRUG

Pharmaceutical form:solution for injection

Route of administration: intramuscular

Step 1 (ACTs)

1 group of paediatric patients will receive arthemeter + lumefantrine (ACTs) bid for 3 days

Group Type: ACTIVE_COMPARATOR

arthemeter + lumefantrine (ACTs)

Intervention Type: DRUG

Pharmaceutical form:tablet

Route of administration: oral

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)

Group Type: EXPERIMENTAL

SAR97276A

Intervention Type: DRUG

Pharmaceutical form:solution for injection

Route of administration: intramuscular

Step 2 (ACTs)

1 group of paediatric patients will receive arthemeter + lumefantrine (ACTs) bid for 3 days

Group Type: ACTIVE_COMPARATOR

arthemeter + lumefantrine (ACTs)

Intervention Type: DRUG

Pharmaceutical form:tablet

Route of administration: oral

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)

Group Type: EXPERIMENTAL

SAR97276A

Intervention Type: DRUG

Pharmaceutical form:solution for injection

Route of administration: intramuscular

Interventions

SAR97276A

Pharmaceutical form:solution for injection

Route of administration: intramuscular

Intervention Type: DRUG

arthemeter + lumefantrine (ACTs)

Pharmaceutical form:tablet

Route of administration: oral

Intervention Type: DRUG

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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 204001

Cotonou, , Benin

Investigational Site Number 854001

Ouagadougou, , Burkina Faso

Investigational Site Number 266001

Libreville, , Gabon

Investigational Site Number 404001

Kisumu, , Kenya

Countries

Benin; Burkina Faso; Gabon; Kenya

References

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.

Reference Type: DERIVED

PMID: 28472957 (View on PubMed)

Other Identifiers

2010-021398-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1118-0694

Identifier Type: OTHER

Identifier Source: secondary_id

PDY11737

Identifier Type: -

Identifier Source: org_study_id