Study of AVE0005 (VEGF Trap) in Patients With Chemoresistant Advanced Ovarian Cancer
Study Details
Study Description
Brief Summary
This study evaluated outcomes in participants with advanced ovarian epithelial adenocarcinoma receiving aflibercept.
The primary objective was to compare the objective response rate of Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) 4.0 mg/kg and 2.0 mg/kg, administered intravenously (IV) every 2 weeks with historical control in participants with advanced ovarian epithelial (including fallopian tube and primary peritoneal) adenocarcinoma resistant to platinum and topotecan and/or liposomal doxorubicin.
The secondary objectives was to further assess efficacy, safety, pharmacokinetics, potential biological and pharmacogenomic markers of study drug activity, and health-related quality of life.
This study employed an Independent Review Committee (IRC) for radiological tumor assessments. For all tumor assessment-related efficacy variables, two analyses were performed: the primary analysis was based on Independent Review Committee (IRC) reviewed data and the secondary analysis was based on Investigator evaluation. If an endpoint was evaluated by the IRC, the IRC reviewed data is reported for this study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The study included:
-
A screening period for 21 days
-
Randomization at baseline (Treatment was initiated with 5 days of randomization)
-
A treatment period with 14-day study treatment cycles until a study withdrawal criterion was met
-
A follow-up period up to 60 days after the end of treatment
Withdrawal criteria that led to treatment discontinuation were:
-
The participant or their legally authorized representative requested to withdraw
-
In the investigator's opinion, continuation of the study would be detrimental to the participant's well being, due to reasons such as disease progression, unacceptable toxicity, noncompliance, or logistical considerations.
-
A specific request by the Sponsor
-
Participant had intercurrent illness that prevented further administration of study treatment
-
Participant had more than 2 aflibercept dose reductions
-
Participant had arterial thromboembolic events, including cerebrovascular accidents, myocardial infarctions, transient ischemic attacks, new onset or worsening of pre-existing angina
-
Participant had radiographic evidence of intestinal obstruction (e.g., dilated loops of bowel accompanied by air-fluid levels) or gastrointestinal perforation (e.g., presence of extraluminal gas) requiring surgical intervention
-
Participant was lost to follow-up
After discontinuing treatment, participants remained on the study until the last post-treatment visit or until recovery of drug related toxicities, whichever was later.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Aflibercept 2.0 mg/kg Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept. |
Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Aflibercept 2.0 mg/kg administered intravenously (IV) over 1 hour once every 2 weeks.
Aflibercept could be reduced by 1 dose level (to 1.0 mg/kg) or 2 dose levels (to 0.5 mg/kg) in case of uncontrolled hypertension or urinary protein >3.5 g/24 hours. Intrapatient dose escalation was not to be permitted. Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.
|
| Experimental: Aflibercept 4.0 mg/kg Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept. |
Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Aflibercept 4.0 mg/kg administered intravenously (IV) over 1 hour once every 2 weeks.
Aflibercept could be reduced by 1 dose level ( to 2.0 mg/kg) or 2 dose levels (to 1.0 mg/kg) in case of uncontrolled hypertension or urinary protein >3.5 g/24 hours. Intrapatient dose escalation was not to be permitted. Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Based on the Analysis by an Independent Review Committee (IRC) - Simon's Cohort [From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)]
OR included Complete Response (CR) and Partial Response (PR). Per RECIST, CR was disappearance of all target or non-target lesions, or normalization of tumor marker levels (for non-target lesions) and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with baseline sum LD as reference. Tumors were assessed by an independent third-party core imaging laboratory evaluating the chest, abdomen, and pelvis by Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and responses were confirmed by repeat tumor imaging 4-6 weeks later.
- Number of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Based on the Analysis by the IRC - Efficacy Evaluable Population [From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)]
OR included Complete Response (CR) and Partial Response (PR). Per RECIST, CR was disappearance of all target or non-target lesions, or normalization of tumor marker levels (for non-target lesions) and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with baseline sum LD as reference. Tumors were assessed by an independent third-party core imaging laboratory evaluating the chest, abdomen, and pelvis by Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and responses were confirmed by repeat tumor imaging 4-6 weeks later.
Secondary Outcome Measures
- Number of Participants With a Clinical Benefit Response (CBR) as Per RECIST Based on the Analysis by the IRC [From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)]
CBR was defined as having a Stable disease (SD) for >= 6 months or a confirmed OR (PR or CR). Based on RECIST: SD was neither a sufficient shrinkage of the target lesions to qualify for PR nor sufficient increase to qualify for Progressive disease (PD), the persistence of non-target lesions or the maintenance of tumor marker level above the normal limits (for non-target lesions) CR was the disappearance of all target or non-target lesions; and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with reference to the baseline sum LD.
- Duration of Response (DR) Based on the Analysis by an Independent Review Committee (IRC) [From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)]
DR was defined as the time interval from the first documentation of CR or PR to the date of tumor progression (or disease progression) as determined by RECIST, or death from any cause, whichever was earlier. Based on RECIST, progressive disease was at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, the appearance of one or more new target or non-target lesions, or the unequivocal progression of existing non-target lesions.
- Tumor Marker Response Rate (TMRR) Based on the Gynecologic Cancer Intergroup (GCIG) Definition [From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)]
TMRR was the proportion of evaluable participants achieving a cancer antigen -125 (CA-125) response based on GCIG definition. A response to CA-125 occurred if after two elevated levels before therapy there was at least a 50% decrease in a post-treatment serum sample, which was confirmed by an independent sample collected 21 days or later that was =< 110% of the post-treatment serum sample.
- Time to Tumor Progression (TTP) as Per RECIST Based on the Analysis by the IRC [From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)]
TTP was defined as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST. TTP was estimated from Kaplan-Meier curves. For a participant who did not reach tumor progression during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization.
- Time to Tumor Marker (CA-125) Progression (TTMP) [From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)]
TTMP was the time interval from the date of randomization to the date of tumor marker progression as was defined by GCIG for the evaluable participants. TTMP was estimated using Kaplan-Meier curves. For a participant who did not reach tumor marker progression (TMP) during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization.
- Number of Participants With Disease Progression Events for Progression-free Survival (PFS) Analysis by the IRC. [From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)]
PFS was as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST or death from any cause, whichever was earlier. The number of participants with tumor/disease progression are reported. Participants who did not reach tumor progression during study, or had no valid post-baseline tumor burden assessment due to early termination, were censored in the PFS analysis.
- Progression-free Survival (PFS) Time Based on Analysis by the IRC [From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)]
PFS was as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST or death from any cause, whichever was earlier. PFS was estimated using Kaplan-Meier curves. For a participant who did not reach tumor progression during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization.
- Overall Survival (OS) Time [From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)]
OS was the time interval between randomization and the date of death from any cause. OS was estimated using Kaplan-Meier curves A participant was censored for the OS analysis if the participant were alive during the study. The censoring date was either at the date that the participant was last known to be alive or the date of study cut-off, whichever was earlier.
- Overall Safety - Number of Participants With Adverse Events (AE) [up to 30+/-5 days after treatment discontinuation, or up to recovery or stabilization of a followed-up adverse event]
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.
- Participant's Assessment of Health Related Quality of Life (HRQL) Using a by Using the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Questionnaire [On Day 1 of Cycle 1 (baseline) , and after Day 14 of Cycle 2]
The FACT-O questionnaire consists of 38 scored questions (scored from 0-4) that address physical well-being, social/family well-being, emotional well-being, functional well-being and some additional concerns which relate specifically to ovarian cancer symptoms. For each question, higher scores reflect a better quality of life. The total FACT-O score ranges from 0-152, with 152 indicating the best outcome.
Eligibility Criteria
Criteria
Participants who met the following criteria were eligible for the study.
Inclusion Criteria:
-
Histologically-confirmed ovarian epithelial (including fallopian tube and primary peritoneal) adenocarcinoma.
-
Prior treatment with at least 2 treatment regimens in the advanced disease treatment setting
-
Platinum-resistant disease defined by relapse or progression of disease during or after treatment, or drug intolerance
-
Topotecan- and/or liposomal doxorubicin-resistant disease defined by relapse or progression of disease during or after treatment, or drug intolerance
-
Evidence of at least one unidimensional measurable tumor lesion by computed tomography (CT) or magnetic resonance imaging (MRI) scan according to Response Evaluation Criteria in Solid Tumors (RECIST) that has not been treated with surgery or radiation therapy
Exclusion Criteria:
-
Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or for in situ carcinoma of the cervix uteri
-
Prior treatment with a vascular endothelial growth factor (VEGF) or VEGF receptor inhibitor
-
More than 3 chemotherapy regimens in the advanced disease treatment setting
-
Uncontrolled hypertension
The above information is not intended to contain all considerations relevant to potential participation in a clinical trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sanofi-Aventis Administrative Office | Bridgewater | New Jersey | United States | 08807 |
| 2 | Sanofi-Aventis Administrative Office | Macquarie Park | Australia | ||
| 3 | Sanofi-Aventis Administrative Office | Laval | Canada | ||
| 4 | Sanofi-Aventis Administrative Office | Paris | France | ||
| 5 | Sanofi-Aventis Administrative Office | Berlin | Germany | ||
| 6 | Sanofi-Aventis Administrative Office | Milano | Italy | ||
| 7 | Sanofi-Aventis Administrative Office | Gouda | Netherlands | ||
| 8 | Sanofi-Aventis Administrative Office | Porto Salvo | Portugal | ||
| 9 | Sanofi-Aventis Administrative Office | Barcelona | Spain | ||
| 10 | Sanofi-Aventis Administrative Office | Bromma | Sweden | ||
| 11 | Sanofi-Aventis Administrative Office | Geneva | Switzerland |
Sponsors and Collaborators
- Sanofi
- Regeneron Pharmaceuticals
Investigators
- Study Director: ICD CSD, Sanofi
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ARD6122
- AVE0005
Study Results
Participant Flow
| Recruitment Details | 218 participants were randomized in this study. Three participants in the 2 mg/kg treatment group did not receive any study medication. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg |
|---|---|---|
| Arm/Group Description | Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks | Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks |
| Period Title: Overall Study | ||
| STARTED | 109 | 109 |
| COMPLETED | 1 | 0 |
| NOT COMPLETED | 108 | 109 |
Baseline Characteristics
| Arm/Group Title | Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg | Total |
|---|---|---|---|
| Arm/Group Description | Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks | Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks | Total of all reporting groups |
| Overall Participants | 109 | 109 | 218 |
| Age, Customized (participants) [Number] | |||
| <35 years |
3
2.8%
|
3
2.8%
|
6
2.8%
|
| >=35 to <45 years |
10
9.2%
|
6
5.5%
|
16
7.3%
|
| >=45 to <55 years |
21
19.3%
|
25
22.9%
|
46
21.1%
|
| >=55 to <65 years |
37
33.9%
|
43
39.4%
|
80
36.7%
|
| >=65 to <75 years |
32
29.4%
|
25
22.9%
|
57
26.1%
|
| >=75 years |
6
5.5%
|
7
6.4%
|
13
6%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
109
100%
|
109
100%
|
218
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| Caucasian |
104
95.4%
|
107
98.2%
|
211
96.8%
|
| Black |
3
2.8%
|
1
0.9%
|
4
1.8%
|
| Asian, Oriental |
1
0.9%
|
1
0.9%
|
2
0.9%
|
| Unknown or Not Reported |
1
0.9%
|
0
0%
|
1
0.5%
|
Outcome Measures
| Title | Number of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Based on the Analysis by an Independent Review Committee (IRC) - Simon's Cohort |
|---|---|
| Description | OR included Complete Response (CR) and Partial Response (PR). Per RECIST, CR was disappearance of all target or non-target lesions, or normalization of tumor marker levels (for non-target lesions) and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with baseline sum LD as reference. Tumors were assessed by an independent third-party core imaging laboratory evaluating the chest, abdomen, and pelvis by Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and responses were confirmed by repeat tumor imaging 4-6 weeks later. |
| Time Frame | From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Simon's cohort: The first 67 evaluable participants, based on Simon's two-stage design that required 67 evaluable participants per group to maintain a targeted 80% power for Objective response rate versus historical controls. |
| Arm/Group Title | Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg |
|---|---|---|
| Arm/Group Description | Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks | Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks |
| Measure Participants | 67 | 67 |
| Number [participants] |
0
0%
|
3
2.8%
|
| Title | Number of Participants With a Clinical Benefit Response (CBR) as Per RECIST Based on the Analysis by the IRC |
|---|---|
| Description | CBR was defined as having a Stable disease (SD) for >= 6 months or a confirmed OR (PR or CR). Based on RECIST: SD was neither a sufficient shrinkage of the target lesions to qualify for PR nor sufficient increase to qualify for Progressive disease (PD), the persistence of non-target lesions or the maintenance of tumor marker level above the normal limits (for non-target lesions) CR was the disappearance of all target or non-target lesions; and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with reference to the baseline sum LD. |
| Time Frame | From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Simon's cohort: The first 67 evaluable participants, based on Simon's two-stage design that required 67 evaluable participants per group to maintain a targeted 80% power for Objective response rate versus historical controls. |
| Arm/Group Title | Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg |
|---|---|---|
| Arm/Group Description | Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks | Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks |
| Measure Participants | 67 | 67 |
| Number [participants] |
12
11%
|
7
6.4%
|
| Title | Duration of Response (DR) Based on the Analysis by an Independent Review Committee (IRC) |
|---|---|
| Description | DR was defined as the time interval from the first documentation of CR or PR to the date of tumor progression (or disease progression) as determined by RECIST, or death from any cause, whichever was earlier. Based on RECIST, progressive disease was at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, the appearance of one or more new target or non-target lesions, or the unequivocal progression of existing non-target lesions. |
| Time Frame | From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy evaluable population: All participants with advanced ovarian epithelial carcinoma who were randomized, underwent baseline tumor assessment, and received at least part of one dose of aflibercept. |
| Arm/Group Title | Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg |
|---|---|---|
| Arm/Group Description | Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks | Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks |
| Measure Participants | 1 | 5 |
| Mean (Standard Deviation) [days] |
164
(NA)
|
149.8
(70.4)
|
| Title | Tumor Marker Response Rate (TMRR) Based on the Gynecologic Cancer Intergroup (GCIG) Definition |
|---|---|
| Description | TMRR was the proportion of evaluable participants achieving a cancer antigen -125 (CA-125) response based on GCIG definition. A response to CA-125 occurred if after two elevated levels before therapy there was at least a 50% decrease in a post-treatment serum sample, which was confirmed by an independent sample collected 21 days or later that was =< 110% of the post-treatment serum sample. |
| Time Frame | From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least part of one dose of aflibercept, had a baseline tumor assessment, had a valid CA-125 assessment (requiring at least two pretreatment sample and 2 post-treatment samples), did not receive mouse antibodies and had no medical or surgical interference with their peritoneum or pleura in the previous 28 days. |
| Arm/Group Title | Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg |
|---|---|---|
| Arm/Group Description | Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks | Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks |
| Measure Participants | 61 | 69 |
| Mean (95% Confidence Interval) [percentage of participants] |
11.5
10.6%
|
11.6
10.6%
|
| Title | Time to Tumor Progression (TTP) as Per RECIST Based on the Analysis by the IRC |
|---|---|
| Description | TTP was defined as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST. TTP was estimated from Kaplan-Meier curves. For a participant who did not reach tumor progression during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization. |
| Time Frame | From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy evaluable population: All participants with advanced ovarian epithelial carcinoma who were randomized, underwent baseline tumor assessment, and received at least part of one dose of aflibercept. |
| Arm/Group Title | Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg |
|---|---|---|
| Arm/Group Description | Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks | Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks |
| Measure Participants | 106 | 109 |
| Measure Tumor Progression Events | 66 | 66 |
| Median (95% Confidence Interval) [weeks] |
13.1
|
12.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Aflibercept 2.0 mg/kg, Aflibercept 4.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5043 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.123 | |
| Confidence Interval |
(2-Sided) 95% 0.80 to 1.58 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated using Cox proportional Hazard model using treatment as the factor | |
| Title | Time to Tumor Marker (CA-125) Progression (TTMP) |
|---|---|
| Description | TTMP was the time interval from the date of randomization to the date of tumor marker progression as was defined by GCIG for the evaluable participants. TTMP was estimated using Kaplan-Meier curves. For a participant who did not reach tumor marker progression (TMP) during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization. |
| Time Frame | From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid assessment of CA-125 (requiring at least one pretreatment sample and 2 post-treatment samples). |
| Arm/Group Title | Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg |
|---|---|---|
| Arm/Group Description | Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks | Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks |
| Measure Participants | 76 | 84 |
| Measure Tumor Marker Progression events | 15 | 20 |
| Median (95% Confidence Interval) [weeks] |
NA
|
NA
|
| Title | Number of Participants With Disease Progression Events for Progression-free Survival (PFS) Analysis by the IRC. |
|---|---|
| Description | PFS was as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST or death from any cause, whichever was earlier. The number of participants with tumor/disease progression are reported. Participants who did not reach tumor progression during study, or had no valid post-baseline tumor burden assessment due to early termination, were censored in the PFS analysis. |
| Time Frame | From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy evaluable population: All participants with advanced ovarian epithelial carcinoma who were randomized, underwent baseline tumor assessment, and received at least part of one dose of aflibercept. |
| Arm/Group Title | Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg |
|---|---|---|
| Arm/Group Description | Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks | Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks |
| Measure Participants | 106 | 109 |
| With disease progression as the first event |
66
60.6%
|
66
60.6%
|
| Death without disease progression |
16
14.7%
|
23
21.1%
|
| Censored due to drop-out |
18
16.5%
|
14
12.8%
|
| Censored at study cut-off |
6
5.5%
|
6
5.5%
|
| Title | Progression-free Survival (PFS) Time Based on Analysis by the IRC |
|---|---|
| Description | PFS was as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST or death from any cause, whichever was earlier. PFS was estimated using Kaplan-Meier curves. For a participant who did not reach tumor progression during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization. |
| Time Frame | From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy evaluable population: All participants with advanced ovarian epithelial carcinoma who were randomized, underwent baseline tumor assessment, and received at least part of one dose of aflibercept. |
| Arm/Group Title | Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg |
|---|---|---|
| Arm/Group Description | Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks | Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks |
| Measure Participants | 106 | 109 |
| Measure PFS Events | 82 | 89 |
| Median (95% Confidence Interval) [weeks] |
13.0
|
13.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Aflibercept 2.0 mg/kg, Aflibercept 4.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5592 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.093 | |
| Confidence Interval |
(2-Sided) 95% 0.81 to 1.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated using Cox proportional Hazard model using treatment as the factor (4mg/kg vs. 2mg/kg) | |
| Title | Overall Survival (OS) Time |
|---|---|
| Description | OS was the time interval between randomization and the date of death from any cause. OS was estimated using Kaplan-Meier curves A participant was censored for the OS analysis if the participant were alive during the study. The censoring date was either at the date that the participant was last known to be alive or the date of study cut-off, whichever was earlier. |
| Time Frame | From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy evaluable population: All participants with advanced ovarian epithelial carcinoma who were randomized, underwent baseline tumor assessment, and received at least part of one dose of aflibercept. |
| Arm/Group Title | Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg |
|---|---|---|
| Arm/Group Description | Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks | Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks |
| Measure Participants | 106 | 109 |
| Measure Events (Death) | 50 | 58 |
| Median (95% Confidence Interval) [weeks] |
59.0
|
49.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Aflibercept 2.0 mg/kg, Aflibercept 4.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5457 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.124 | |
| Confidence Interval |
(2-Sided) 95% 0.77 to 1.64 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated using Cox proportional Hazard model using treatment as the factor (4 mg/kg vs. 2mg/kg) | |
| Title | Number of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Based on the Analysis by the IRC - Efficacy Evaluable Population |
|---|---|
| Description | OR included Complete Response (CR) and Partial Response (PR). Per RECIST, CR was disappearance of all target or non-target lesions, or normalization of tumor marker levels (for non-target lesions) and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with baseline sum LD as reference. Tumors were assessed by an independent third-party core imaging laboratory evaluating the chest, abdomen, and pelvis by Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and responses were confirmed by repeat tumor imaging 4-6 weeks later. |
| Time Frame | From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy evaluable population: All participants with advanced ovarian epithelial carcinoma who were randomized, underwent baseline tumor assessment, and received at least part of one dose of aflibercept. |
| Arm/Group Title | Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg |
|---|---|---|
| Arm/Group Description | Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks | Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks |
| Measure Participants | 106 | 109 |
| Number [participants] |
1
0.9%
|
5
4.6%
|
| Title | Overall Safety - Number of Participants With Adverse Events (AE) |
|---|---|
| Description | 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. |
| Time Frame | up to 30+/-5 days after treatment discontinuation, or up to recovery or stabilization of a followed-up adverse event |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population: All randomized participants who received at least part of one dose of study treatment. |
| Arm/Group Title | Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg |
|---|---|---|
| Arm/Group Description | Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks | Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks |
| Measure Participants | 106 | 109 |
| With any TEAE |
106
97.2%
|
108
99.1%
|
| With any serious TEAE |
50
45.9%
|
55
50.5%
|
| With any TEAE leading to death |
14
12.8%
|
14
12.8%
|
| With TEAE leading to treatment discontinuation |
23
21.1%
|
24
22%
|
| Title | Participant's Assessment of Health Related Quality of Life (HRQL) Using a by Using the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Questionnaire |
|---|---|
| Description | The FACT-O questionnaire consists of 38 scored questions (scored from 0-4) that address physical well-being, social/family well-being, emotional well-being, functional well-being and some additional concerns which relate specifically to ovarian cancer symptoms. For each question, higher scores reflect a better quality of life. The total FACT-O score ranges from 0-152, with 152 indicating the best outcome. |
| Time Frame | On Day 1 of Cycle 1 (baseline) , and after Day 14 of Cycle 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who had evaluable FACT-O questionnaires. |
| Arm/Group Title | Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg |
|---|---|---|
| Arm/Group Description | Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks | Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks |
| Measure Participants | 97 | 104 |
| Baseline (N=97, N=104) |
105.3
(20.0)
|
101.1
(22)
|
| Change (baseline to Cycle 2-Day 14) (N=79, N=77) |
-1.1
(12.7)
|
-2.8
(13.9)
|
Adverse Events
| Time Frame | From treatment initiation to June 9, 2010 | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety population: All randomized participants who received at least part of one dose of study treatment. | |||
| Arm/Group Title | Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg | ||
| Arm/Group Description | Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks | Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks | ||
All Cause Mortality |
||||
| Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 51/106 (48.1%) | 56/109 (51.4%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 2/106 (1.9%) | 1/109 (0.9%) | ||
| Thrombocytopenia | 1/106 (0.9%) | 0/109 (0%) | ||
| Thrombotic thrombocytopenic purpura | 0/106 (0%) | 1/109 (0.9%) | ||
| Cardiac disorders | ||||
| Angina pectoris | 1/106 (0.9%) | 0/109 (0%) | ||
| Cardio-respiratory arrest | 1/106 (0.9%) | 0/109 (0%) | ||
| Congestive cardiomyopathy | 1/106 (0.9%) | 0/109 (0%) | ||
| Left ventricular dysfunction | 0/106 (0%) | 1/109 (0.9%) | ||
| Ear and labyrinth disorders | ||||
| Vertigo | 0/106 (0%) | 1/109 (0.9%) | ||
| Eye disorders | ||||
| Blindness transient | 0/106 (0%) | 1/109 (0.9%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 4/106 (3.8%) | 6/109 (5.5%) | ||
| Ascites | 1/106 (0.9%) | 0/109 (0%) | ||
| Colonic obstruction | 1/106 (0.9%) | 0/109 (0%) | ||
| Crohn's disease | 1/106 (0.9%) | 0/109 (0%) | ||
| Diarrhoea | 1/106 (0.9%) | 1/109 (0.9%) | ||
| Gastrointestinal haemorrhage | 0/106 (0%) | 1/109 (0.9%) | ||
| Gastrointestinal necrosis | 1/106 (0.9%) | 0/109 (0%) | ||
| Gastrointestinal obstruction | 2/106 (1.9%) | 1/109 (0.9%) | ||
| Intestinal obstruction | 10/106 (9.4%) | 6/109 (5.5%) | ||
| Intestinal perforation | 1/106 (0.9%) | 2/109 (1.8%) | ||
| Melaena | 1/106 (0.9%) | 0/109 (0%) | ||
| Nausea | 3/106 (2.8%) | 0/109 (0%) | ||
| Small intestinal obstruction | 0/106 (0%) | 2/109 (1.8%) | ||
| Subileus | 0/106 (0%) | 2/109 (1.8%) | ||
| Vomiting | 2/106 (1.9%) | 2/109 (1.8%) | ||
| General disorders | ||||
| Asthenia | 1/106 (0.9%) | 2/109 (1.8%) | ||
| Disease progression | 3/106 (2.8%) | 7/109 (6.4%) | ||
| Fatigue | 0/106 (0%) | 1/109 (0.9%) | ||
| General physical health deterioration | 0/106 (0%) | 2/109 (1.8%) | ||
| Pyrexia | 2/106 (1.9%) | 2/109 (1.8%) | ||
| Sudden death | 0/106 (0%) | 1/109 (0.9%) | ||
| Hepatobiliary disorders | ||||
| Jaundice cholestatic | 1/106 (0.9%) | 0/109 (0%) | ||
| Infections and infestations | ||||
| Abscess intestinal | 0/106 (0%) | 1/109 (0.9%) | ||
| Appendicitis | 0/106 (0%) | 1/109 (0.9%) | ||
| Catheter site infection | 0/106 (0%) | 1/109 (0.9%) | ||
| Clostridial infection | 0/106 (0%) | 1/109 (0.9%) | ||
| Clostridium difficile colitis | 0/106 (0%) | 1/109 (0.9%) | ||
| Device related infection | 1/106 (0.9%) | 0/109 (0%) | ||
| Febrile infection | 1/106 (0.9%) | 1/109 (0.9%) | ||
| Gastroenteritis salmonella | 1/106 (0.9%) | 0/109 (0%) | ||
| Hepatitis a | 0/106 (0%) | 1/109 (0.9%) | ||
| Peritonitis bacterial | 0/106 (0%) | 1/109 (0.9%) | ||
| Pneumonia | 2/106 (1.9%) | 2/109 (1.8%) | ||
| Pneumonia streptococcal | 1/106 (0.9%) | 0/109 (0%) | ||
| Pyelonephritis | 0/106 (0%) | 1/109 (0.9%) | ||
| Sepsis | 1/106 (0.9%) | 0/109 (0%) | ||
| Septic shock | 1/106 (0.9%) | 0/109 (0%) | ||
| Urinary tract infection | 1/106 (0.9%) | 0/109 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Ankle fracture | 0/106 (0%) | 1/109 (0.9%) | ||
| Narcotic intoxication | 0/106 (0%) | 1/109 (0.9%) | ||
| Wound dehiscence | 0/106 (0%) | 1/109 (0.9%) | ||
| Investigations | ||||
| Blood alkaline phosphatase increased | 1/106 (0.9%) | 0/109 (0%) | ||
| Blood creatinine increased | 1/106 (0.9%) | 0/109 (0%) | ||
| Gamma-glutamyltransferase increased | 1/106 (0.9%) | 0/109 (0%) | ||
| Hepatic enzyme increased | 1/106 (0.9%) | 0/109 (0%) | ||
| International normalised ratio increased | 0/106 (0%) | 1/109 (0.9%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 2/106 (1.9%) | 0/109 (0%) | ||
| Dehydration | 4/106 (3.8%) | 2/109 (1.8%) | ||
| Hypoalbuminaemia | 1/106 (0.9%) | 0/109 (0%) | ||
| Hyponatraemia | 1/106 (0.9%) | 1/109 (0.9%) | ||
| Type 1 diabetes mellitus | 0/106 (0%) | 1/109 (0.9%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 0/106 (0%) | 1/109 (0.9%) | ||
| Musculoskeletal chest pain | 0/106 (0%) | 1/109 (0.9%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Cardiac myxoma | 1/106 (0.9%) | 0/109 (0%) | ||
| Malignant pleural effusion | 1/106 (0.9%) | 0/109 (0%) | ||
| Metastases to central nervous system | 0/106 (0%) | 2/109 (1.8%) | ||
| Metastases to lymph nodes | 1/106 (0.9%) | 0/109 (0%) | ||
| Metastases to small intestine | 0/106 (0%) | 1/109 (0.9%) | ||
| Nervous system disorders | ||||
| Grand mal convulsion | 0/106 (0%) | 1/109 (0.9%) | ||
| Headache | 1/106 (0.9%) | 2/109 (1.8%) | ||
| Hypertensive encephalopathy | 0/106 (0%) | 1/109 (0.9%) | ||
| Polyneuropathy | 0/106 (0%) | 1/109 (0.9%) | ||
| Syncope | 1/106 (0.9%) | 0/109 (0%) | ||
| Transient ischaemic attack | 1/106 (0.9%) | 0/109 (0%) | ||
| Renal and urinary disorders | ||||
| Hydronephrosis | 1/106 (0.9%) | 0/109 (0%) | ||
| Nephrotic syndrome | 1/106 (0.9%) | 0/109 (0%) | ||
| Proteinuria | 1/106 (0.9%) | 1/109 (0.9%) | ||
| Renal failure | 3/106 (2.8%) | 3/109 (2.8%) | ||
| Renal failure acute | 0/106 (0%) | 1/109 (0.9%) | ||
| Urinary retention | 1/106 (0.9%) | 0/109 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory distress syndrome | 1/106 (0.9%) | 0/109 (0%) | ||
| Chronic obstructive pulmonary disease | 0/106 (0%) | 1/109 (0.9%) | ||
| Dyspnoea | 2/106 (1.9%) | 4/109 (3.7%) | ||
| Hypoxia | 1/106 (0.9%) | 0/109 (0%) | ||
| Pleural effusion | 3/106 (2.8%) | 1/109 (0.9%) | ||
| Pneumonia aspiration | 0/106 (0%) | 1/109 (0.9%) | ||
| Pulmonary embolism | 1/106 (0.9%) | 2/109 (1.8%) | ||
| Pulmonary oedema | 0/106 (0%) | 1/109 (0.9%) | ||
| Respiratory failure | 1/106 (0.9%) | 0/109 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Erythema | 0/106 (0%) | 1/109 (0.9%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 0/106 (0%) | 1/109 (0.9%) | ||
| Hypertension | 4/106 (3.8%) | 6/109 (5.5%) | ||
| Phlebitis | 0/106 (0%) | 1/109 (0.9%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Aflibercept 2.0 mg/kg | Aflibercept 4.0 mg/kg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 105/106 (99.1%) | 106/109 (97.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 6/106 (5.7%) | 2/109 (1.8%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 36/106 (34%) | 40/109 (36.7%) | ||
| Abdominal pain upper | 14/106 (13.2%) | 17/109 (15.6%) | ||
| Constipation | 37/106 (34.9%) | 27/109 (24.8%) | ||
| Diarrhoea | 31/106 (29.2%) | 39/109 (35.8%) | ||
| Dry mouth | 6/106 (5.7%) | 4/109 (3.7%) | ||
| Intestinal obstruction | 8/106 (7.5%) | 4/109 (3.7%) | ||
| Nausea | 44/106 (41.5%) | 43/109 (39.4%) | ||
| Stomatitis | 10/106 (9.4%) | 8/109 (7.3%) | ||
| Toothache | 9/106 (8.5%) | 7/109 (6.4%) | ||
| Vomiting | 38/106 (35.8%) | 30/109 (27.5%) | ||
| General disorders | ||||
| Asthenia | 30/106 (28.3%) | 27/109 (24.8%) | ||
| Fatigue | 42/106 (39.6%) | 44/109 (40.4%) | ||
| Mucosal inflammation | 13/106 (12.3%) | 19/109 (17.4%) | ||
| Oedema peripheral | 12/106 (11.3%) | 12/109 (11%) | ||
| Pyrexia | 18/106 (17%) | 21/109 (19.3%) | ||
| Infections and infestations | ||||
| Nasopharyngitis | 7/106 (6.6%) | 9/109 (8.3%) | ||
| Urinary tract infection | 13/106 (12.3%) | 5/109 (4.6%) | ||
| Investigations | ||||
| Weight decreased | 8/106 (7.5%) | 11/109 (10.1%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 42/106 (39.6%) | 30/109 (27.5%) | ||
| Dehydration | 3/106 (2.8%) | 9/109 (8.3%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 25/106 (23.6%) | 28/109 (25.7%) | ||
| Back pain | 15/106 (14.2%) | 10/109 (9.2%) | ||
| Muscle spasms | 2/106 (1.9%) | 7/109 (6.4%) | ||
| Musculoskeletal pain | 15/106 (14.2%) | 13/109 (11.9%) | ||
| Myalgia | 8/106 (7.5%) | 17/109 (15.6%) | ||
| Neck pain | 8/106 (7.5%) | 6/109 (5.5%) | ||
| Pain in extremity | 9/106 (8.5%) | 8/109 (7.3%) | ||
| Nervous system disorders | ||||
| Dizziness | 9/106 (8.5%) | 12/109 (11%) | ||
| Headache | 54/106 (50.9%) | 54/109 (49.5%) | ||
| Neuropathy peripheral | 8/106 (7.5%) | 4/109 (3.7%) | ||
| Paraesthesia | 6/106 (5.7%) | 8/109 (7.3%) | ||
| Psychiatric disorders | ||||
| Anxiety | 4/106 (3.8%) | 7/109 (6.4%) | ||
| Depression | 3/106 (2.8%) | 7/109 (6.4%) | ||
| Insomnia | 8/106 (7.5%) | 11/109 (10.1%) | ||
| Renal and urinary disorders | ||||
| Proteinuria | 21/106 (19.8%) | 23/109 (21.1%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 10/106 (9.4%) | 21/109 (19.3%) | ||
| Dysphonia | 39/106 (36.8%) | 46/109 (42.2%) | ||
| Dyspnoea | 15/106 (14.2%) | 20/109 (18.3%) | ||
| Epistaxis | 8/106 (7.5%) | 21/109 (19.3%) | ||
| Oropharyngeal pain | 7/106 (6.6%) | 11/109 (10.1%) | ||
| Rhinorrhoea | 4/106 (3.8%) | 7/109 (6.4%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Nail disorder | 4/106 (3.8%) | 6/109 (5.5%) | ||
| Rash | 10/106 (9.4%) | 9/109 (8.3%) | ||
| Vascular disorders | ||||
| Hypertension | 60/106 (56.6%) | 57/109 (52.3%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The investigator shall have the right to independently publish study results from his site after a multicenter publication, or 12 months after the completion of the study by all sites. He must provide the sponsor a copy of any such publication derived from the study, for review and comment at least 45 days in advance of any submission, and delay publication till the approval of the publication is given in writing by the Sponsor (not to exceed ninety days).
Results Point of Contact
| Name/Title | Trial Transparency Team |
|---|---|
| Organization | Sanofi |
| Phone | |
| Contact-Us@sanofi.com |
- ARD6122
- AVE0005