Clinical Trial Results:
A Long-Term Follow-up Study Assessing the Safety and Efficacy of Vatelizumab in Multiple Sclerosis (MS) Patients Who Completed Treatment in Study DRI13839
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Summary
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EudraCT number |
2014-003265-19 |
Trial protocol |
PL |
Global end of trial date |
21 Apr 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Jul 2017
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First version publication date |
22 Jul 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
LTS13840
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02306811 | ||
WHO universal trial number (UTN) |
U1111-1160-6120 | ||
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Sponsors
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Sponsor organisation name |
Genzyme Corporation
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Sponsor organisation address |
500 Kendall Street, Cambridge, MA, United States, 02142
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Public contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 Nov 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Apr 2016
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To assess the long-term safety of vatelizumab in multiple sclerosis (MS) subjects.
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Protection of trial subjects |
Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial, the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Feb 2015
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
2 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Russian Federation: 29
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Country: Number of subjects enrolled |
United States: 11
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Country: Number of subjects enrolled |
Canada: 2
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Country: Number of subjects enrolled |
Poland: 20
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Worldwide total number of subjects |
62
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EEA total number of subjects |
20
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
62
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted in 4 countries between 03 February 2015 and 21 April 2016. Subjects who completed 12-week treatment in the DRI13839 study (EudraCT no. 2014-001643-20) were offered to participate in this long-term study LTS13480. | ||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Subjects who completed 12-week treatment for vatelizumab (1600 mg, 1200 mg, 800 mg or 400 mg) in DRI13839 study, continued on the same dose in the LTS13480 study and 24 subjects who completed 12-week treatment for placebo in DRI13839 study were randomized in 1:1:1:1 ratio to vatelizumab treatment groups (1600 mg, 1200 mg, 800 mg or 400 mg). | ||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | ||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo to Vatelizumab (1600 mg, 1200 mg, 800 mg, or 400 mg) | ||||||||||||||||||||||||||||
Arm description |
Subjects who received placebo in DRI13839 study were randomized in 1:1:1:1 ratio to vatelizumab 1600 mg (6 subjects), vatelizumab 1200 mg (6 subjects), vatelizumab 800 mg (6 subjects) and vatelizumab 400 mg (6 subjects). Subjects received vatelizumab (1600 mg, 1200 mg, 800 mg or 400 mg) IV infusion once every 4 weeks for 96 weeks. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Vatelizumab
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Investigational medicinal product code |
SAR339658
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Intravenous infusion over a 60 minutes period.
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Arm title
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Vatelizumab 1600 mg | ||||||||||||||||||||||||||||
Arm description |
Vatelizumab 1600 mg IV infusion once every 4 weeks for 96 weeks. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Vatelizumab
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Investigational medicinal product code |
SAR339658
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Intravenous infusion over a 60 minutes period.
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Arm title
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Vatelizumab 1200 mg, 800 mg, or 400 mg | ||||||||||||||||||||||||||||
Arm description |
Vatelizumab 1200 mg, 800 mg or 400 mg IV infusion once every 4 weeks for 96 weeks. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Vatelizumab
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Investigational medicinal product code |
SAR339658
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Intravenous infusion over a 60 minutes period.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo to Vatelizumab (1600 mg, 1200 mg, 800 mg, or 400 mg)
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Reporting group description |
Subjects who received placebo in DRI13839 study were randomized in 1:1:1:1 ratio to vatelizumab 1600 mg (6 subjects), vatelizumab 1200 mg (6 subjects), vatelizumab 800 mg (6 subjects) and vatelizumab 400 mg (6 subjects). Subjects received vatelizumab (1600 mg, 1200 mg, 800 mg or 400 mg) IV infusion once every 4 weeks for 96 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Vatelizumab 1600 mg
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Reporting group description |
Vatelizumab 1600 mg IV infusion once every 4 weeks for 96 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Vatelizumab 1200 mg, 800 mg, or 400 mg
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Reporting group description |
Vatelizumab 1200 mg, 800 mg or 400 mg IV infusion once every 4 weeks for 96 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo to Vatelizumab (1600 mg, 1200 mg, 800 mg, or 400 mg)
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Reporting group description |
Subjects who received placebo in DRI13839 study were randomized in 1:1:1:1 ratio to vatelizumab 1600 mg (6 subjects), vatelizumab 1200 mg (6 subjects), vatelizumab 800 mg (6 subjects) and vatelizumab 400 mg (6 subjects). Subjects received vatelizumab (1600 mg, 1200 mg, 800 mg or 400 mg) IV infusion once every 4 weeks for 96 weeks. | ||
Reporting group title |
Vatelizumab 1600 mg
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Reporting group description |
Vatelizumab 1600 mg IV infusion once every 4 weeks for 96 weeks. | ||
Reporting group title |
Vatelizumab 1200 mg, 800 mg, or 400 mg
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Reporting group description |
Vatelizumab 1200 mg, 800 mg or 400 mg IV infusion once every 4 weeks for 96 weeks. | ||
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End point title |
Percentage of Subjects With Treatment Emergent Adverse Events (TEAEs) [1] | ||||||||||||||||||||||||
End point description |
Any untoward medical occurrence in subject who received study drug was considered an adverse event (AE) without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from first administration of study drug to end of safety follow-up period [Week 192]). Serious adverse event (SAE) was defined as any untoward medical occurrence resulted in any of following: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included subjects with both serious and non-serious AEs. Related AEs were those related or possibly related by investigator and subjects were only counted once. Safety population:all subjects entered into study LTS13840 and analyzed based on treatment actually received.
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End point type |
Primary
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End point timeframe |
From randomization up to end of study visit (Week 192)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: As the endpoint is descriptive in nature, no statistical analysis is provided. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Brain Magnetic Resonance Imaging (MRI) Assessment: Cumulative Number of New Gadolinium Enhancing (Gd-enhancing) T1-lesions Per MRI Scan | ||||||||||||||||||||||||||||
End point description |
Cumulative number of Gd-enhancing T1-lesions per scan were the total number of Gd-enhancing T1-lesions that occurred during the treatment period divided by the total number of scans performed during the treatment period. Analysis was performed on safety population. Here, 'n' signifies number of subjects with available data for specified timepoint and "99999" represents no subject analyzed at specified timepoint.
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End point type |
Secondary
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End point timeframe |
Week 12, Week 32 and end of treatment (EOT) (maximum exposure: 225 days)
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Brain MRI Assessment: Cumulative Number of New or Newly Enlarging T2-lesions Per MRI Scan | ||||||||||||||||||||||||||||
End point description |
Cumulative number of new or newly enlarging T2-lesions per scan were the total number of new or newly enlarging T2-lesions that occurred during the treatment period divided by the total number of scans performed during the treatment period. Analysis was performed on safety population. Here, 'n' signifies number of subjects with available data for specified timepoint and "99999" represents no subject analyzed at specified timepoint.
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End point type |
Secondary
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End point timeframe |
Week 12, Week 32 and EOT (maximum exposure: 225 days)
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Blood Lymphocyte Sub-population Count: CD4+ Cells, CD8+ Cells, and CD19+ Cells | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Analysis was performed on pharmacokinetics/pharmacodynamics population that included all subjects who entered into and received at least 1 dose of investigational medicinal product (IMP) in the extension study LTS13840. Subjects were analyzed based on the treatment that they actually received. Here, 'n' signifies number of subjects with available data for specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline (Week 0), Week 4, Week 100, Week 108
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Blood Lymphocyte Sub-Population: CD4+/CD8+ Cells Ratio | ||||||||||||||||||||||||||||||||
End point description |
Analysis was performed on pharmacokinetics/pharmacodynamics population. Subjects were analyzed based on the treatment that they actually received. Here, 'n' signifies number of subjects with available data for specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline (Week 0), Week 4, Week 100, Week 108
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||
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End point title |
Pharmacokinetics: Plasma Concentration of Vatelizumab | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected for determination of plasma vatelizumab concentration at Week 0, 4, 8 and 12 prior to the start of infusion and at the end of infusion. EOT data is for plasma level determinations that were performed at the time of early study termination (at time of Investigator decision to stop treatment or Sponsor decision to stop the study) and thus, represent different study visits/timepoints. Analysis was performed on safety population. Here, 'n' signifies number of subjects with available data for specified timepoints and and "99999" represents no subject analyzed at specified timepoint.
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End point type |
Secondary
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End point timeframe |
Week 0, 4, 8 , 12 (pre-dose and any time after the end of infusion); Week 24, Week 96/EOT (pre-dose) and Week 100 (anytime)
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
All AEs were collected from signature of the informed consent form up to the final visit (Week 192) regardless of seriousness or relationship to study drug.
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Adverse event reporting additional description |
Reported AEs are TEAEs that is AEs that developed/worsened during the ‘on treatment period’ (time from the first administration of study drug to the end of safety follow-up period [Week 192]).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
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Reporting groups
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Reporting group title |
Placebo to Vatelizumab (1600 mg, 1200 mg, 800 mg or 400 mg)
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Reporting group description |
Subjects who received placebo in DRI13839 study were randomized in 1:1:1:1 ratio to vatelizumab 1600 mg (6 subjects), vatelizumab 1200 mg (6 subjects), vatelizumab 800 mg (6 subjects) and vatelizumab 400 mg (6 subjects). Subjects received vatelizumab (1600 mg, 1200 mg, 800 mg or 400 mg) IV infusion once every 4 weeks for 96 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Vatelizumab 1600 mg
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Reporting group description |
Vatelizumab 1600 mg IV infusion once every 4 weeks for 96 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Vatelizumab 1200 mg, 800 mg or 400 mg
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Reporting group description |
Vatelizumab 1200 mg, 800 mg or 400 mg IV infusion once every 4 weeks for 96 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| As per sponsor’s decision, study was discontinued in October 2015 based on planned interim analysis of the primary endpoint. However, subjects were followed up for safety monitoring. Decision for discontinuation was not linked to any safety concern. | |||
