Aflibercept Versus Placebo in Combination With Irinotecan and 5-FU in the Treatment of Patients With Metastatic Colorectal Cancer After Failure of an Oxaliplatin Based Regimen

Phase 3

Completed

Conditions: Colorectal Neoplasms
Neoplasm Metastasis

Interventions: Drug: Placebo
Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Drug: FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)

Registration Number: NCT00561470

Lead Sponsor: Sanofi

Brief Summary: The main objective of the study was to evaluate the effectiveness of aflibercept (versus placebo) in increasing the overall survival in participants with metastatic colorectal cancer treated with FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) and that have previously failed an oxaliplatin based treatment for metastatic disease.

The secondary objectives were to compare progression-free survival, to evaluate overall response rate, to evaluate the safety profile, to assess immunogenicity of intravenous (IV) aflibercept, and to assess pharmacokinetics of IV aflibercept in both treatment arms.

Detailed Description: Participants were

* randomized at baseline (treatment was initiated with 3 days of randomization)

* administered treatment in cycles of 14-days till a study withdrawal criterion was met

* followed up 30 days after discontinuation of treatment, and every 8 weeks until death or end of study.

The criteria for discontinuation of study treatment for a participant are:

* participant (or legal representative) chose to withdraw from treatment

* the investigator thought that continuation of the study would be detrimental to the participants well-being due to

* disease progression

* unacceptable AEs

* intercurrent illnesses

* non-compliance to the study protocol

* participant was lost to follow-up

* participant was unblinded for the investigational treatment

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1226

Inclusion Criteria

Histologically or cytologically proven adenocarcinoma of the colon or rectum
Metastatic disease that is not amenable to potentially curative treatment
One and only one prior line of treatment for metastatic disease. This prior line should be an oxaliplatin based chemotherapy (participants who relapse within 6 months of completion of oxaliplatin based adjuvant chemotherapy are eligible)
Prior treatment with bevacizumab is permitted.

Exclusion Criteria

Prior therapy with irinotecan
Eastern Cooperative Oncology Group performance status >2

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo/FOLFIRI	Placebo	Participants with Metastatic Colorectal Cancer administered Placebo followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) starting on Day 1 of a 2-week cycle until a treatment discontinuation criterion was met
Placebo/FOLFIRI	FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)	Participants with Metastatic Colorectal Cancer administered Placebo followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) starting on Day 1 of a 2-week cycle until a treatment discontinuation criterion was met
Aflibercept/FOLFIRI	Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)	Participants with Metastatic Colorectal Cancer administered Aflibercept followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) starting on Day 1 of a 2-week cycle until a treatment discontinuation criterion was met
Aflibercept/FOLFIRI	FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)	Participants with Metastatic Colorectal Cancer administered Aflibercept followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) starting on Day 1 of a 2-week cycle until a treatment discontinuation criterion was met

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From the date of the first randomization until the study data cut-off date, 07 February 2011 (approximately three years)	Overall Survival was the time interval from the date of randomization to the date of death due to any cause. Once disease progression was documented, participants were followed every 2 months for survival status, until death or until the study cutoff date, whichever came first. The final data cutoff date for the analysis of OS was the date when 863 deaths had occurred (07 February 2011). OS was estimated using the Kaplan-Meier method, and the Hazard Ratio was estimated using the Cox Proportional Hazard Model.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) Assessed by Independent Review Committee (IRC)	From the date of the first randomization until the occurrence of 561 OS events, 06 May 2010 (approximately 30 months)	PFS was the time interval from the date of randomization to the date of progression, or death from any cause if it occurs before tumor progression is documented. To evaluate disease progression, copies of all tumor imaging sets were systematically collected and assessed by the IRC. PFS was analyzed using the Kaplan-Meier method, and the Hazard Ratio was estimated using the Cox Proportional Hazard Model. The analysis for PFS was performed as planned when 561 deaths (OS events) had occurred.
Overall Objective Response Rate (ORR) Based on the Tumor Assessment by the Independent Review Committee (IRC) as Per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria	From the date of the first randomization until the study data cut-off date, 06 May 2010 (approximately 30 months)	The overall ORR was the percentage of evaluable participants who achieved complete response \[CR\] or partial response \[PR\] according to RECIST criteria version 1.0. * CR reflected the disappearance of all tumor lesions (with no new tumors) * PR reflected a pre-defined reduction in tumor burden Tumors were assessed by the IRC using Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and an observed response was confirmed by repeated imaging after 4 - 6 weeks.
Number of Participants With Adverse Events (AE)	From the date of the first randomization up to 30 days after the treatment discontinuation or until TEAE was resolved or stabilized	All AEs regardless of seriousness or relationship to study treatment, spanning from the first administration of study treatment until 30 days after the last administration of study treatment, were recorded, and followed until resolution or stabilization. The number of participants with all treatment emergent adverse events (TEAE), serious adverse events (SAE), TEAE leading to death, and TEAE leading to permanent treatment discontinuation are reported.
Immunogenicity Assessment: Number of Participants With Positive Sample(s) in the Anti-drug Antibodies (ADA) Assay and in the Neutralizing Anti-drug Antibodies (NAb) Assay	Baseline, every other treatment cycle, 30 days and 90 days after the last infusion of aflibercept/placebo	Serum samples for immunogenicity assessment were analyzed using a bridging immunoassay to detect ADA. Positive samples in the ADA assay were further analyzed in the NAb assay using a validated, non-quantitative ligand binding assay.

Trial Locations

Locations (221): Sanofi-Aventis Investigational Site Number 840076
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Fountain Valley, California, United States
Sanofi-Aventis Investigational Site Number 840071
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Stamford, Connecticut, United States
Sanofi-Aventis Investigational Site Number 840096
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Paducah, Kentucky, United States
Sanofi-Aventis Investigational Site Number 840097
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Syracuse, New York, United States
Sanofi-Aventis Investigational Site Number 840033
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Philadelphia, Pennsylvania, United States
Sanofi-Aventis Investigational Site Number 840015
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New Orleans, Louisiana, United States
Sanofi-Aventis Investigational Site Number 840029
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Salisbury, Maryland, United States
Sanofi-Aventis Investigational Site Number 840037
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Spartanburg, South Carolina, United States
Sanofi-Aventis Investigational Site Number 840084
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Metairie, Louisiana, United States
Sanofi-Aventis Investigational Site Number 840070
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Rockville, Maryland, United States
Sanofi-Aventis Investigational Site Number 056002
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Bruxelles, Belgium
Sanofi-Aventis Investigational Site Number 203002
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Brno, Czech Republic
Sanofi-Aventis Investigational Site Number 300005
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Athens, Greece
Sanofi-Aventis Investigational Site Number 300004
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Athens, Greece
Sanofi-Aventis Investigational Site Number 578001
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Oslo, Norway
Sanofi-Aventis Investigational Site Number 578003
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Stavanger, Norway
Sanofi-Aventis Investigational Site Number 643003
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Saint-Petersburg, Russian Federation
Sanofi-Aventis Investigational Site Number 804004
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Donetsk, Ukraine
Sanofi-Aventis Investigational Site Number 840012
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Pittsburgh, Pennsylvania, United States
Sanofi-Aventis Investigational Site Number 840099
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Seattle, Washington, United States
Sanofi-Aventis Investigational Site Number 840106
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San Diego, California, United States
Sanofi-Aventis Investigational Site Number 840206
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San Diego, California, United States
Sanofi-Aventis Investigational Site Number 840506
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San Diego, California, United States
Sanofi-Aventis Investigational Site Number 840606
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San Diego, California, United States
Sanofi-Aventis Investigational Site Number 840401
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San Francisco, California, United States
Sanofi-Aventis Investigational Site Number 840098
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Cincinnati, Ohio, United States
Sanofi-Aventis Investigational Site Number 208003
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Ålborg, Denmark
Sanofi-Aventis Investigational Site Number 380005
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Aviano, Italy
Sanofi-Aventis Investigational Site Number 380003
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Genova, Italy
Sanofi-Aventis Investigational Site Number 840119
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Birmingham, Alabama, United States
Sanofi-Aventis Investigational Site Number 840039
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Portland, Oregon, United States
Sanofi-Aventis Investigational Site Number 840094
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Lake Success, New York, United States
Sanofi-Aventis Investigational Site Number 840086
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Middletown, Ohio, United States
Sanofi-Aventis Investigational Site Number 840082
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Pawtucket, Rhode Island, United States
Sanofi-Aventis Investigational Site Number 840112
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Salinas, California, United States
Sanofi-Aventis Investigational Site Number 840201
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Oakland, California, United States
Sanofi-Aventis Investigational Site Number 840047
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Indianapolis, Indiana, United States
Sanofi-Aventis Investigational Site Number 840306
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San Diego, California, United States
Sanofi-Aventis Investigational Site Number 840088
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Louisville, Kentucky, United States
Sanofi-Aventis Investigational Site Number 840034
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Munster, Indiana, United States
Sanofi-Aventis Investigational Site Number 840074
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Muscle Shoals, Alabama, United States
Sanofi-Aventis Investigational Site Number 840093
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Hot Springs, Arizona, United States
Sanofi-Aventis Investigational Site Number 840116
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Loma Linda, California, United States
Sanofi-Aventis Investigational Site Number 840042
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Sacramento, California, United States
Sanofi-Aventis Investigational Site Number 840101
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Hayward, California, United States
Sanofi-Aventis Investigational Site Number 840501
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Santa Clara, California, United States
Sanofi-Aventis Investigational Site Number 840801
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South San Francisco, California, United States
Sanofi-Aventis Investigational Site Number 840601
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San Jose, California, United States
Sanofi-Aventis Investigational Site Number 840806
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San Diego, California, United States
Sanofi-Aventis Investigational Site Number 840906
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San Diego, California, United States
Sanofi-Aventis Investigational Site Number 840001
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Vallejo, California, United States
Sanofi-Aventis Investigational Site Number 840014
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Newark, Delaware, United States
Sanofi-Aventis Investigational Site Number 840087
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Chicago, Illinois, United States
Sanofi-Aventis Investigational Site Number 840122
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Miami, Florida, United States
Sanofi-Aventis Investigational Site Number 840041
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Gainesville, Florida, United States
Sanofi-Aventis Investigational Site Number 840089
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Boynton Beach, Florida, United States
Sanofi-Aventis Investigational Site Number 840079
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The Villages, Florida, United States
Sanofi-Aventis Investigational Site Number 840019
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Decatur, Illinois, United States
Sanofi-Aventis Investigational Site Number 840115
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Elk Grove Village, Illinois, United States
Sanofi-Aventis Investigational Site Number 840113
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Quincy, Illinois, United States
Sanofi-Aventis Investigational Site Number 840043
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Baton Rouge, Louisiana, United States
Sanofi-Aventis Investigational Site Number 040001
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Wien, Austria
Sanofi-Aventis Investigational Site Number 840081
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Kansas City, Missouri, United States
Sanofi-Aventis Investigational Site Number 056003
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Leuven, Belgium
Sanofi-Aventis Investigational Site Number 840002
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Marshfield, Wisconsin, United States
Sanofi-Aventis Investigational Site Number 840053
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Pontiac, Michigan, United States
Sanofi-Aventis Investigational Site Number 840005
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Goldsboro, North Carolina, United States
Sanofi-Aventis Investigational Site Number 840008
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Toledo, Ohio, United States
Sanofi-Aventis Investigational Site Number 840004
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Hendersonville, North Carolina, United States
Sanofi-Aventis Investigational Site Number 840052
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St Louis, Missouri, United States
Sanofi-Aventis Investigational Site Number 840036
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Albany, New York, United States
Sanofi-Aventis Investigational Site Number 840049
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Las Vegas, Nevada, United States
Sanofi-Aventis Investigational Site Number 840024
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Charlotte, North Carolina, United States
Sanofi-Aventis Investigational Site Number 840095
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Woonsocket, Rhode Island, United States
Sanofi-Aventis Investigational Site Number 840085
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Charleston, South Carolina, United States
Sanofi-Aventis Investigational Site Number 032006
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Buenos Aires, Argentina
Sanofi-Aventis Investigational Site Number 032005
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Ciudad De Buenos Aires, Argentina
Sanofi-Aventis Investigational Site Number 036006
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Subiaco, Australia
Sanofi-Aventis Investigational Site Number 840011
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Kettering, Ohio, United States
Sanofi-Aventis Investigational Site Number 032007
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Salta, Argentina
Sanofi-Aventis Investigational Site Number 840078
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Corpus Christi, Texas, United States
Sanofi-Aventis Investigational Site Number 036002
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Kurralta Park, Australia
Sanofi-Aventis Investigational Site Number 032003
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Bahia Blanca, Argentina
Sanofi-Aventis Investigational Site Number 056007
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Bruxelles, Belgium
Sanofi-Aventis Investigational Site Number 056001
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Gent, Belgium
Sanofi-Aventis Investigational Site Number 056005
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Haine-Saint-Paul, Belgium
Sanofi-Aventis Investigational Site Number 076005
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Porto Alegre, Brazil
Sanofi-Aventis Investigational Site Number 076007
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Sao Paulo, Brazil
Sanofi-Aventis Investigational Site Number 380007
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Ancona, Italy
Sanofi-Aventis Investigational Site Number 380001
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Milano, Italy
Sanofi-Aventis Investigational Site Number 380002
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Milano, Italy
Sanofi-Aventis Investigational Site Number 380008
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Rozzano, Italy
Sanofi-Aventis Investigational Site Number 380006
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San Giovanni Rotondo, Italy
Sanofi-Aventis Investigational Site Number 076006
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Sao Paulo, Brazil
Sanofi-Aventis Investigational Site Number 410003
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Seoul, Korea, Republic of
Sanofi-Aventis Investigational Site Number 410001
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Goyang, Korea, Republic of
Sanofi-Aventis Investigational Site Number 410005
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Seoul, Korea, Republic of
Sanofi-Aventis Investigational Site Number 233001
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Tartu, Estonia
Sanofi-Aventis Investigational Site Number 250003
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Paris, France
Sanofi-Aventis Investigational Site Number 276005
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Magdeburg, Germany
Sanofi-Aventis Investigational Site Number 300001
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Heraklion, Greece
Sanofi-Aventis Investigational Site Number 300003
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Patras, Greece
Sanofi-Aventis Investigational Site Number 380004
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Candiolo, Italy
Sanofi-Aventis Investigational Site Number 528001
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Blaricum, Netherlands
Sanofi-Aventis Investigational Site Number 410002
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Seoul, Korea, Republic of
Sanofi-Aventis Investigational Site Number 528005
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Breda, Netherlands
Sanofi-Aventis Investigational Site Number 528002
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Rotterdam, Netherlands
Sanofi-Aventis Investigational Site Number 554009
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Auckland, New Zealand
Sanofi-Aventis Investigational Site Number 528003
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Sittard-Geleen, Netherlands
Sanofi-Aventis Investigational Site Number 578002
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Bergen, Norway
Sanofi-Aventis Investigational Site Number 554010
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Christchurch, New Zealand
Sanofi-Aventis Investigational Site Number 630001
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San Juan, Puerto Rico
Sanofi-Aventis Investigational Site Number 642007
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Bucharest, Romania
Sanofi-Aventis Investigational Site Number 642005
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Suceava, Romania
Sanofi-Aventis Investigational Site Number 724003
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Madrid, Spain
Sanofi-Aventis Investigational Site Number 643004
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St-Petersburg, Russian Federation
Sanofi-Aventis Investigational Site Number 710006
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Port Elizabeth, South Africa
Sanofi-Aventis Investigational Site Number 710001
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Parktown, South Africa
Sanofi-Aventis Investigational Site Number 710005
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Durban, South Africa
Sanofi-Aventis Investigational Site Number 710003
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Pretoria, South Africa
Sanofi-Aventis Investigational Site Number 724005
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Barcelona, Spain
Sanofi-Aventis Investigational Site Number 724001
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Barcelona, Spain
Sanofi-Aventis Investigational Site Number 710007
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Pretoria, South Africa
Sanofi-Aventis Investigational Site Number 724006
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Madrid, Spain
Sanofi-Aventis Investigational Site Number 724007
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Reus, Spain
Sanofi-Aventis Investigational Site Number 752002
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Stockholm, Sweden
Sanofi-Aventis Investigational Site Number 752003
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Sundsvall, Sweden
Sanofi-Aventis Investigational Site Number 752001
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Uppsala, Sweden
Sanofi-Aventis Investigational Site Number 792005
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Adana, Turkey
Sanofi-Aventis Investigational Site Number 804002
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Kharkov, Ukraine
Sanofi-Aventis Investigational Site Number 826001
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Aberdeen, United Kingdom
Sanofi-Aventis Investigational Site Number 826010
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Bournemouth, United Kingdom
Sanofi-Aventis Investigational Site Number 826009
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Dudley, United Kingdom
Sanofi-Aventis Investigational Site Number 826008
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London, United Kingdom
Sanofi-Aventis Investigational Site Number 826004
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London, United Kingdom
Sanofi-Aventis Investigational Site Number 840072
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Indianapolis, Indiana, United States
Sanofi-Aventis Investigational Site Number 840026
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Charlotte, North Carolina, United States
Sanofi-Aventis Investigational Site Number 840046
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La Jolla, California, United States
Sanofi-Aventis Investigational Site Number 840701
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Walnut Creek, California, United States
Sanofi-Aventis Investigational Site Number 276006
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München, Germany
Sanofi-Aventis Investigational Site Number 840120
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Fountain Valley, California, United States
Sanofi-Aventis Investigational Site Number 840114
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St. Louis, Missouri, United States
Sanofi-Aventis Investigational Site Number 840048
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Long Beach, California, United States
Sanofi-Aventis Investigational Site Number 724002
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Barakaldo, Spain
Sanofi-Aventis Investigational Site Number 410004
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Seoul, Korea, Republic of
Sanofi-Aventis Investigational Site Number 840080
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Anaheim, California, United States
Sanofi-Aventis Investigational Site Number 840301
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Sacramento, California, United States
Sanofi-Aventis Investigational Site Number 840073
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Greenbrae, California, United States
Sanofi-Aventis Investigational Site Number 840006
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San Diego, California, United States
Sanofi-Aventis Investigational Site Number 840706
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San Diego, California, United States
Sanofi-Aventis Investigational Site Number 840901
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Roseville, California, United States
Sanofi-Aventis Investigational Site Number 840406
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San Diego, California, United States
Sanofi-Aventis Investigational Site Number 840031
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Gainesville, Florida, United States
Sanofi-Aventis Investigational Site Number 840010
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Naperville, Illinois, United States
Sanofi-Aventis Investigational Site Number 840044
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Albuquerque, New Mexico, United States
Sanofi-Aventis Investigational Site Number 840021
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St Louis Park, Minnesota, United States
Sanofi-Aventis Investigational Site Number 840017
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Syracuse, New York, United States
Sanofi-Aventis Investigational Site Number 840035
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Burlington, North Carolina, United States
Sanofi-Aventis Investigational Site Number 840118
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Bethlehem, Pennsylvania, United States
Sanofi-Aventis Investigational Site Number 036001
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Kingswood, Australia
Sanofi-Aventis Investigational Site Number 036004
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Hornsby, Australia
Sanofi-Aventis Investigational Site Number 840075
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Winston-Salem, North Carolina, United States
Sanofi-Aventis Investigational Site Number 840117
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Temple, Texas, United States
Sanofi-Aventis Investigational Site Number 036005
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Melbourne, Australia
Sanofi-Aventis Investigational Site Number 036003
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Melbourne, Australia
Sanofi-Aventis Investigational Site Number 056006
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Bonheiden, Belgium
Sanofi-Aventis Investigational Site Number 036007
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Nedlands, Australia
Sanofi-Aventis Investigational Site Number 056004
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Bruxelles, Belgium
Sanofi-Aventis Investigational Site Number 076004
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Porto Alegre, Brazil
Sanofi-Aventis Investigational Site Number 076002
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Porto Alegre, Brazil
Sanofi-Aventis Investigational Site Number 076008
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Rio De Janeiro, Brazil
Sanofi-Aventis Investigational Site Number 076003
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Rio De Janeiro, Brazil
Sanofi-Aventis Investigational Site Number 076001
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Santo Andre, Brazil
Sanofi-Aventis Investigational Site Number 152002
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Santiago, Chile
Sanofi-Aventis Investigational Site Number 152005
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Santiago, Chile
Sanofi-Aventis Investigational Site Number 152004
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Viña Del Mar, Chile
Sanofi-Aventis Investigational Site Number 152001
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Santiago, Chile
Sanofi-Aventis Investigational Site Number 152003
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Santiago, Chile
Sanofi-Aventis Investigational Site Number 203001
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Brno, Czech Republic
Sanofi-Aventis Investigational Site Number 203004
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Praha 5, Czech Republic
Sanofi-Aventis Investigational Site Number 233002
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Tallinn, Estonia
Sanofi-Aventis Investigational Site Number 208001
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Odense C, Denmark
Sanofi-Aventis Investigational Site Number 250002
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Brest, France
Sanofi-Aventis Investigational Site Number 250004
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Clichy Cx, France
Sanofi-Aventis Investigational Site Number 250005
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La Roche Sur Yon, France
Sanofi-Aventis Investigational Site Number 276003
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Aschaffenburg, Germany
Sanofi-Aventis Investigational Site Number 276002
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Essen, Germany
Sanofi-Aventis Investigational Site Number 250001
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Lyon Cedex 03, France
Sanofi-Aventis Investigational Site Number 528004
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Amsterdam, Netherlands
Sanofi-Aventis Investigational Site Number 276001
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Halle / Saale, Germany
Sanofi-Aventis Investigational Site Number 300002
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Ilion, Athens, Greece
Sanofi-Aventis Investigational Site Number 276004
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Magdeburg, Germany
Sanofi-Aventis Investigational Site Number 616004
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Elblag, Poland
Sanofi-Aventis Investigational Site Number 616002
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Poznan, Poland
Sanofi-Aventis Investigational Site Number 616007
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Krakow, Poland
Sanofi-Aventis Investigational Site Number 616003
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Lodz, Poland
Sanofi-Aventis Investigational Site Number 616005
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Czestochowa, Poland
Sanofi-Aventis Investigational Site Number 616006
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Rybnik, Poland
Sanofi-Aventis Investigational Site Number 616001
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Wroclaw, Poland
Sanofi-Aventis Investigational Site Number 642002
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Bucuresti, Romania
Sanofi-Aventis Investigational Site Number 642006
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Iasi, Romania
Sanofi-Aventis Investigational Site Number 642004
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Alba Iulia, Romania
Sanofi-Aventis Investigational Site Number 642003
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Cluj Napoca, Romania
Sanofi-Aventis Investigational Site Number 642001
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Bucuresti, Romania
Sanofi-Aventis Investigational Site Number 643001
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Moscow, Russian Federation
Sanofi-Aventis Investigational Site Number 643006
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Moscow, Russian Federation
Sanofi-Aventis Investigational Site Number 643002
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Moscow, Russian Federation
Sanofi-Aventis Investigational Site Number 710008
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Durban, South Africa
Sanofi-Aventis Investigational Site Number 710004
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Cape Town, South Africa
Sanofi-Aventis Investigational Site Number 643007
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St-Petersburg, Russian Federation
Sanofi-Aventis Investigational Site Number 792004
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Ankara, Turkey
Sanofi-Aventis Investigational Site Number 792001
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Ankara, Turkey
Sanofi-Aventis Investigational Site Number 792002
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Izmir, Turkey
Sanofi-Aventis Investigational Site Number 804005
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Dnipropetrovsk, Ukraine
Sanofi-Aventis Investigational Site Number 792003
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Kayseri, Turkey
Sanofi-Aventis Investigational Site Number 804006
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Kharkiv, Ukraine
Sanofi-Aventis Investigational Site Number 826003
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Northwood, United Kingdom
Sanofi-Aventis Investigational Site Number 826002
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Manchester, United Kingdom
Sanofi-Aventis Investigational Site Number 826005
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Sutton, United Kingdom
Sanofi-Aventis Investigational Site Number 826007
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London, United Kingdom
Sanofi-Aventis Investigational Site Number 826011
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London, United Kingdom