Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 5 of 103 for:    "Kennedy disease"

Safety, Tolerability, and Efficacy of BVS857 in Patients With Spinal and Bulbar Muscular Atrophy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02024932
Recruitment Status : Completed
First Posted : December 31, 2013
Results First Posted : August 11, 2017
Last Update Posted : August 18, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Spinal and Bulbar Muscular Atrophy
Interventions Drug: BVS857
Drug: Placebo
Enrollment 37
Recruitment Details This study was conducted in 2 parts, Part A and Part B. In Part A, Cohort 1 participants received open-label BVS857. Cohort 2 participants were randomized to double-blind BVS857 or double-blind placebo in a 2:1 ratio.
Pre-assignment Details In Part B, Cohort 3 was not enrolled. Cohort 4 participants received open-label BVS857. Cohort 5 participants were randomized to double-blind BVS857 or double-blind placebo in a ratio of 18:10.
Arm/Group Title BVS857 Part A Open Label (Cohort 1) BVS857 Part A Double Blind (Cohort 2) Placebo Part A Double Blind (Cohort 2) BVS857 Part B Open-label (Cohort 4) BVS857 Part B Double Blind (Cohort 5) Placebo Part B Double Blind (Cohort 5)
Hide Arm/Group Description Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.) Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57. Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks. Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks. Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
Period Title: Overall Study
Started 2 4 2 2 18 9
Safety Analysis Set 2 4 2 2 18 9
Pharmacokinetic (PK) Analysis Set 2 4 0 2 18 0
Pharmacodynamic (PD) Analysis Set 2 4 2 2 18 9
Completed 0 1 2 0 16 9
Not Completed 2 3 0 2 2 0
Reason Not Completed
Adverse Event             2             3             0             0             2             0
Abnormal laboratory value             0             0             0             2             0             0
Arm/Group Title BVS857 Part A Open Label (Cohort 1) BVS857 Part A Double Blind (Cohort 2) Placebo Part A Double Blind (Cohort 2) BVS857 Part B Open-label (Cohort 4) BVS857 Part B Double Blind (Cohort 5) Placebo Part B Double Blind (Cohort 5) Total
Hide Arm/Group Description Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.) Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57. Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks. Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks. Participants received matching placebo i.v. to BVS857 weekly for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 2 4 2 2 18 9 37
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2 participants 4 participants 2 participants 2 participants 18 participants 9 participants 37 participants
67.0  (5.66) 56.0  (12.33) 59.5  (7.78) 41.5  (4.95) 57.0  (55.5) 54.0  (5.94) 56.0  (10.33)
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Male Number Analyzed 2 participants 4 participants 2 participants 2 participants 18 participants 9 participants 37 participants
2 4 2 2 18 9 37
1.Primary Outcome
Title Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability
Hide Description Safety was monitored throughout the study.
Time Frame After 78 days in Part A and after 85 days in Part B.
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set, which included participants who received any study drug, was analyzed.
Arm/Group Title BVS857 Part A Open Label (Cohort 1) BVS857 Part A Double Blind (Cohort 2) Placebo Part A Double Blind (Cohort 2) BVS857 Part B Open-label (Cohort 4) BVS857 Part B Double Blind (Cohort 5) Placebo Part B Double Blind (Cohort 5)
Hide Arm/Group Description:
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
Overall Number of Participants Analyzed 2 4 2 2 18 9
Measure Type: Number
Unit of Measure: Participants
Non-serious AEs 2 4 2 1 17 8
SAEs 0 0 0 0 0 0
Deaths 0 0 0 0 0 0
2.Primary Outcome
Title Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability
Hide Description Safety was monitored throughout the study.
Time Frame After 78 days in Part A and after 85 days in Part B.
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set, which included participants who received any study drug, was analyzed.
Arm/Group Title BVS857 Part A Open Label (Cohort 1) BVS857 Part A Double Blind (Cohort 2) Placebo Part A Double Blind (Cohort 2) BVS857 Part B Open-label (Cohort 4) BVS857 Part B Double Blind (Cohort 5) Placebo Part B Double Blind (Cohort 5)
Hide Arm/Group Description:
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
Overall Number of Participants Analyzed 2 4 2 2 18 9
Measure Type: Number
Unit of Measure: Participants
Mild 1 2 2 0 5 4
Moderate 1 2 0 0 11 3
Severe 0 0 0 0 1 1
3.Primary Outcome
Title Mean Percent Change From Baseline in Thigh Muscle Volume in Part B, Cohort 5
Hide Description Thigh muscle volume was assessed by magnetic resonance imaging (MRI). Change from baseline was calculated from the ratio of the post-baseline mean value to the baseline mean value: [(Day 85/baseline) - 1)] x 100. A positive change from baseline indicates improvement.
Time Frame Baseline, Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
The PD analysis set was considered for the analysis. However, only participants who had evaluable data at both baseline and day 85, were included in the analysis. The PD set included participants with evaluable PD data who received any study drug and had no protocol deviations with relevant impact on PD data.
Arm/Group Title BVS857 Part B Double Blind (Cohort 5) Placebo Part B Double Blind (Cohort 5)
Hide Arm/Group Description:
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
Overall Number of Participants Analyzed 15 9
Mean (Standard Deviation)
Unit of Measure: Percent change
0.0  (2.42) -3.4  (4.79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BVS857 Part B Double Blind (Cohort 5), Placebo Part B Double Blind (Cohort 5)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0164
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Geo-mean ratio
Estimated Value 1.037
Confidence Interval (2-Sided) 90%
1.009 to 1.065
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Mean Change From Baseline in Score on the Adult Myopathy Assessment Tool (AMAT) in Part B, Cohort 5
Hide Description The AMAT rated physical function and muscle endurance, with higher scores indicating better performance. The tool includes 7 timed functional tasks rated on a scale from 0 - 21 and 6 endurance tasks rated on a scale from 0 - 24. The range for the total score was from 0 (worst) to 45 (best). A positive change from baseline indicates improvement.
Time Frame Baseline, Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
The PD set included, which included participants with evaluable PD data who received any study drug and had no protocol deviations with relevant impact on PD data, was analyzed.
Arm/Group Title BVS857 Part B Double Blind (Cohort 5) Placebo Part B Double Blind (Cohort 5)
Hide Arm/Group Description:
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
Overall Number of Participants Analyzed 18 9
Mean (Standard Deviation)
Unit of Measure: score on a scale
1.0  (4.20) 2.3  (1.87)
5.Secondary Outcome
Title Mean Change From Baseline in Total Lean Body Mass (LBM) in Part B, Cohort 5
Hide Description LBM was assessed by dual-energy X-ray (DXA) absorptiometry. A positive change from baseline indicate improvement.
Time Frame Baseline, Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
The PD analysis set was considered for the analysis. However, only participants who had evaluable data at both baseline and day 85, were included in the analysis. The PD set included participants with evaluable PD data who received any study drug and had no protocol deviations with relevant impact on PD data.
Arm/Group Title BVS857 Part B Double Blind (Cohort 5) Placebo Part B Double Blind (Cohort 5)
Hide Arm/Group Description:
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
Overall Number of Participants Analyzed 17 8
Mean (Standard Deviation)
Unit of Measure: kilograms
0.77  (1.556) 0.16  (1.199)
6.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 1
Hide Description Serum samples were obtained for PK assessment.
Time Frame Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Arm/Group Title BVS857 Part A Open Label (Cohort 1)
Hide Arm/Group Description:
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1, 0.01 mg/kg BVS857 i.v. 184  (6.36)
Day 15, 0.01 mg/kg BVS857 s.c. 34.6  (48.9)
Day 29, 0.03 mg/kg BVS857 s.c 83.1  (20.3)
Day 43, 0.06 mg/kg BVS857 s.c. 74.2  (16.1)
7.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 2
Hide Description Serum samples were obtained for PK assessment.
Time Frame Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Arm/Group Title BVS857 Part A Double Blind (Cohort 2)
Hide Arm/Group Description:
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1, 0.03 mg/kg BVS857 i.v. (n=4) 393  (30.1)
Day 15, 0.03 mg/kg BVS857 s.c. (n=3) 77.3  (46.5)
Day 29, 0.06 mg/kg BVS857 s.c. (n=2) 113  (2.12)
Day 43, 0.10 mg/kg BVS857 s.c. (n=3) 191  (19.2)
Day 57, 0.10 mg/kg BVS857 s.c. (n=1) 232 [1]   (NA)
[1]
Standard deviation does not apply when n = 1.
8.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 1
Hide Description Serum samples were obtained for PK assessment.
Time Frame Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Arm/Group Title BVS857 Part A Open Label (Cohort 1)
Hide Arm/Group Description:
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: hours
Day 1, 0.01 mg/kg BVS857 i.v. (n=2) 4.04  (0.0566)
Day 15, 0.01 mg/kg BVS857 s.c. (n=1) 12.1 [1]   (NA)
Day 29, 0.03 mg/kg BVS857 s.c.(n=2) 18.1  (8.41)
Day 43, 0.06 mg/kg BVS857 s.c. (n=2) 36.0  (16.8)
[1]
Standard deviation does not apply when n = 1.
9.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 2
Hide Description Serum samples were obtained for PK assessment.
Time Frame Day 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Arm/Group Title BVS857 Part A Double Blind (Cohort 2)
Hide Arm/Group Description:
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: hours
Day 1, 0.03 mg/kg BVS857 i.v. (n=4) 2.53  (1.70)
Day 15, 0.03 mg/kg BVS857 s.c.(n=3) 24.1  (0.100)
Day 29, 0.06 mg/kg BVS857 s.c. (n=2) 24.0  (0)
Day 43, 0.10 mg/kg BVS857 s.c. (n=3) 24.0  (0.200)
Day 57, 0.10 mg/kg BVS857 s.c. (n=1) 48.0 [1]   (NA)
[1]
Standard deviation does not apply when n = 1.
10.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 1
Hide Description Serum samples were obtained for PK assessment.
Time Frame Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Arm/Group Title BVS857 Part A Open Label (Cohort 1)
Hide Arm/Group Description:
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
Day 1, 0.01 mg/kg BVS857 i.v.(n=2) 4630  (1200)
Day 15, 0.01 mg/kg BVS857 s.c. (n=2) 1060  (1500)
Day 29, 0.03 mg/kg BVS857 s.c.(n=2) 2720  (870)
Day 43, 0.06 mg/kg BVS857 s.c.(n=2) 5310  (4720)
11.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 2
Hide Description Serum samples were obtained for PK assessment.
Time Frame Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Arm/Group Title BVS857 Part A Double Blind (Cohort 2)
Hide Arm/Group Description:
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: H*ng/mL
Day 1, 0.03 mg/kg BVS857 i.v.(n=4) 9850  (4480)
Day 15, 0.03 mg/kg BVS857 s.c. (n=3) 6480  (5850)
Day 29, 0.06 mg/kg BVS857 s.c. (n=2) 7340  (5610)
Day 43, 0.10 mg/kg BVS857 s.c. (n=3) 14400  (3320)
Day 57, 0.10 mg/kg BVS857 s.c. (n=1) 28400 [1]   (NA)
[1]
Standard deviation does not apply when n = 1.
12.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 1
Hide Description Serum samples were obtained for PK assessment.
Time Frame Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Arm/Group Title BVS857 Part A Open Label (Cohort 1)
Hide Arm/Group Description:
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
Day 1, 0.01 mg/kg BVS857 i.v.(n=2) 4620  (1200)
Day 15, 0.01 mg/kg BVS857 s.c. (n=1) 2120 [1]   (NA)
Day 29, 0.03 mg/kg BVS857 s.c. (n=2) 2720  (870)
Day 43, 0.06 mg/kg BVS857 s.c. (n=2) 2210  (339)
[1]
Standard deviation does not apply when n = 1.
13.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 2
Hide Description Serum samples were obtained for PK assessment.
Time Frame Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Arm/Group Title BVS857 Part A Double Blind (Cohort 2)
Hide Arm/Group Description:
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
Day 1, 0.03 mg/kg BVS857 i.v. (n=4) 7980  (1710)
Day 15, 0.03 mg/kg BVS857 s.c. (n=3) 2640  (1500)
Day 29, 0.06 mg/kg BVS857 s.c. (n=2) 3880  (735)
Day 43, 0.10 mg/kg BVS857 s.c. (n=3) 6390  (925)
Day 57, 0.10 mg/kg BVS857 s.c. (n=1) 7360 [1]   (NA)
[1]
Standard deviation does not apply when n = 1.
14.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 4
Hide Description Serum samples were obtained for PK assessment.
Time Frame Days 1: pre-dose, 1, 4, 24, 48 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set, which included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data, was analyzed.
Arm/Group Title BVS857 Part B Open-label (Cohort 4)
Hide Arm/Group Description:
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: ng/mL
2490  (799)
15.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 5
Hide Description Serum samples were obtained for PK assessment.
Time Frame Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Arm/Group Title BVS857 Part B Double Blind (Cohort 5)
Hide Arm/Group Description:
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
Overall Number of Participants Analyzed 18
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1, 0.06 mg/kg BVS857 i.v. (n=18) 854  (669)
Day 36, 0.06 mg/kg BVS857 i.v. (n=16) 790  (184)
Day 78, 0.06 mg/kg BVS857 i.v. (n=16) 712  (218)
16.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 4
Hide Description Serum samples were obtained for PK assessment.
Time Frame Days 1: pre-dose, 1, 4, 24, 48 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set, which included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data, was analyzed.
Arm/Group Title BVS857 Part B Open-label (Cohort 4)
Hide Arm/Group Description:
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: hours
1.08  (0.0707)
17.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 5
Hide Description Serum samples were obtained for PK assessment.
Time Frame Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Arm/Group Title BVS857 Part B Double Blind (Cohort 5)
Hide Arm/Group Description:
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
Overall Number of Participants Analyzed 18
Mean (Standard Deviation)
Unit of Measure: hours
Day 1, 0.06 mg/kg BVS857 i.v. (n=18) 2.39  (1.54)
Day 36, 0.06 mg/kg BVS857 i.v. (n=16) 1.73  (1.20)
Day 78, 0.06 mg/kg BVS857 i.v. (n=16) 1.49  (1.04)
18.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part B, Cohort 5
Hide Description Serum samples were obtained for PK assessment.
Time Frame Day 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Arm/Group Title BVS857 Part B Double Blind (Cohort 5)
Hide Arm/Group Description:
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
Overall Number of Participants Analyzed 18
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
Day 36, 0.06 mg/kg BVS857 i.v. (n=1) 13100 [1]   (NA)
Day 78, 0.06 mg/kg BVS857 i.v. (n=15) 28000  (13500)
[1]
Standard deviation does not apply when n = 1.
19.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 4
Hide Description Serum samples were obtained for the PK assessment.
Time Frame Days 1: pre-dose, 1, 4, 24, 48 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set, which included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data, was analyzed.
Arm/Group Title BVS857 Part B Open-label (Cohort 4)
Hide Arm/Group Description:
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: H*ng/mL
40600  (1270)
20.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 5
Hide Description [Not Specified]
Time Frame Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
Arm/Group Title BVS857 Part B Double Blind (Cohort 5)
Hide Arm/Group Description:
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
Overall Number of Participants Analyzed 18
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
Day 1, 0.06 mg/kg BVS857 i.v. (n=18) 19400  (4160)
Day 36, 0.06 mg/kg BVS857 i.v.(n=16) 19600  (5240)
Day 78, 0.06 mg/kg BVS857 i.v. (n=16) 18100  (5850)
21.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau)
Hide Description Serum samples were obtained for PK assessment.
Time Frame Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
This PK parameter was not analyzed in either Part A or Part B because there were insufficient data points after Cmax. Therefore, this parameter could not be calculated.
Arm/Group Title BVS857 Part A Open Label (Cohort 1) BVS857 Part A Double Blind (Cohort 2) BVS857 Part B Open-label (Cohort 4) BVS857 Part B Double Blind (Cohort 5)
Hide Arm/Group Description:
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
22.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857: The Terminal Elimination Half-life (T1/2)
Hide Description Serum samples were obtained for PK assessment.
Time Frame Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
This PK parameter was not analyzed in either Part A or Part B because there were insufficient data points after Cmax. Therefore, this parameter could not be calculated.
Arm/Group Title BVS857 Part A Open Label (Cohort 1) BVS857 Part A Double Blind (Cohort 2) BVS857 Part B Open-label (Cohort 4) BVS857 Part B Double Blind (Cohort 5)
Hide Arm/Group Description:
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
23.Secondary Outcome
Title Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf)
Hide Description Serum samples were obtained for PK assessment.
Time Frame Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
This PK parameter was not analyzed in either Part A or Part B because there were insufficient data points after Cmax. Therefore, this parameter could not be calculated.
Arm/Group Title BVS857 Part A Open Label (Cohort 1) BVS857 Part A Double Blind (Cohort 2) BVS857 Part B Open-label (Cohort 4) BVS857 Part B Double Blind (Cohort 5)
Hide Arm/Group Description:
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
24.Secondary Outcome
Title Compare Dose Normalized Log-transformed AUCinf Following IV and SC Administrations
Hide Description Serum samples were obtained for PK assessment.
Time Frame In Part A: days 1 and 15, pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
This PK parameter was not analyzed in either Part A or Part B because there were insufficient data points after Cmax. Therefore, this parameter could not be calculated.
Arm/Group Title BVS857 Part A Open Label (Cohort 1) BVS857 Part A Double Blind (Cohort 2) BVS857 Part B Open-label (Cohort 4) BVS857 Part B Double Blind (Cohort 5)
Hide Arm/Group Description:
Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57.
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.)
Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.
Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title BVS857 Part A Open Label (Cohort 1) Placebo Part A Double Blind (Cohort 2) BVS857 Part A Double Blind (Cohort 2) BVS857 Part B Open-label (Cohort 4) BVS857 Part B Double Blind (Cohort 5) Placebo Part B Double Blind (Cohort 5)
Hide Arm/Group Description Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57. Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.) Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks. Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks. Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.
All-Cause Mortality
BVS857 Part A Open Label (Cohort 1) Placebo Part A Double Blind (Cohort 2) BVS857 Part A Double Blind (Cohort 2) BVS857 Part B Open-label (Cohort 4) BVS857 Part B Double Blind (Cohort 5) Placebo Part B Double Blind (Cohort 5)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
BVS857 Part A Open Label (Cohort 1) Placebo Part A Double Blind (Cohort 2) BVS857 Part A Double Blind (Cohort 2) BVS857 Part B Open-label (Cohort 4) BVS857 Part B Double Blind (Cohort 5) Placebo Part B Double Blind (Cohort 5)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/2 (0.00%)   0/2 (0.00%)   0/4 (0.00%)   0/2 (0.00%)   0/18 (0.00%)   0/9 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
BVS857 Part A Open Label (Cohort 1) Placebo Part A Double Blind (Cohort 2) BVS857 Part A Double Blind (Cohort 2) BVS857 Part B Open-label (Cohort 4) BVS857 Part B Double Blind (Cohort 5) Placebo Part B Double Blind (Cohort 5)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/2 (100.00%)   2/2 (100.00%)   4/4 (100.00%)   1/2 (50.00%)   17/18 (94.44%)   8/9 (88.89%) 
Ear and labyrinth disorders             
Eustachian tube dysfunction  1  0/2 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Eye disorders             
Eyelid haematoma  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Glaucoma  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Ocular discomfort  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Scleral hyperaemia  1  0/2 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Vision blurred  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Gastrointestinal disorders             
Constipation  1  0/2 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Diarrhoea  1  1/2 (50.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Flatulence  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Gastrooesophageal reflux disease  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Gingival pain  1  0/2 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Lip disorder  1  0/2 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Lip oedema  1  0/2 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Nausea  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  1/9 (11.11%) 
Oesophagitis  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Paraesthesia oral  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Periodontal disease  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Sensitivity of teeth  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Toothache  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Vomiting  1  1/2 (50.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
General disorders             
Administration site hypersensitivity  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Asthenia  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Catheter site extravasation  1  0/2 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Fatigue  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  2/18 (11.11%)  0/9 (0.00%) 
Feeling hot  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Infusion site erythema  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Infusion site pruritus  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Injection site erythema  1  2/2 (100.00%)  0/2 (0.00%)  3/4 (75.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Injection site rash  1  0/2 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Injection site swelling  1  0/2 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Malaise  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Puncture site pain  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  2/18 (11.11%)  0/9 (0.00%) 
Pyrexia  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Therapeutic response unexpected  1  2/2 (100.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Infections and infestations             
Bronchitis  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Gastroenteritis  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Influenza  1  0/2 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Nasopharyngitis  1  0/2 (0.00%)  2/2 (100.00%)  1/4 (25.00%)  0/2 (0.00%)  4/18 (22.22%)  1/9 (11.11%) 
Upper respiratory tract infection  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Injury, poisoning and procedural complications             
Bone contusion  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Fall  1  1/2 (50.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Fibula fracture  1  0/2 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Road traffic accident  1  1/2 (50.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Sunburn  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/2 (50.00%)  0/18 (0.00%)  0/9 (0.00%) 
Wound  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Investigations             
Blood potassium increased  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Blood pressure increased  1  0/2 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Neutralising antibodies positive  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  2/18 (11.11%)  0/9 (0.00%) 
Weight increased  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Metabolism and nutrition disorders             
Gout  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Musculoskeletal and connective tissue disorders             
Arthralgia  1  1/2 (50.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  1/9 (11.11%) 
Back pain  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  2/9 (22.22%) 
Exostosis of jaw  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Joint stiffness  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Muscle spasms  1  1/2 (50.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Muscular weakness  1  1/2 (50.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  2/18 (11.11%)  0/9 (0.00%) 
Musculoskeletal pain  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  1/9 (11.11%) 
Myalgia  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Spinal pain  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Melanocytic naevus  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Seborrhoeic keratosis  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Nervous system disorders             
Carotid artery stenosis  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Dizziness  1  0/2 (0.00%)  0/2 (0.00%)  2/4 (50.00%)  0/2 (0.00%)  2/18 (11.11%)  0/9 (0.00%) 
Headache  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  3/18 (16.67%)  1/9 (11.11%) 
Hypoaesthesia  1  1/2 (50.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Paraesthesia  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  2/18 (11.11%)  0/9 (0.00%) 
Presyncope  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Somnolence  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Psychiatric disorders             
Irritability  1  1/2 (50.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Panic attack  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Bronchospasm  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Choking  1  1/2 (50.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Oropharyngeal pain  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/18 (0.00%)  1/9 (11.11%) 
Upper respiratory tract congestion  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Skin and subcutaneous tissue disorders             
Acne  1  0/2 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Dermatitis contact  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Erythema  1  0/2 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  1/18 (5.56%)  1/9 (11.11%) 
Pruritus  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  0/9 (0.00%) 
Skin discolouration  1  0/2 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Skin irritation  1  0/2 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Vascular disorders             
Flushing  1  1/2 (50.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Hypertension  1  0/2 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  1/18 (5.56%)  1/9 (11.11%) 
Hypotension  1  1/2 (50.00%)  0/2 (0.00%)  0/4 (0.00%)  0/2 (0.00%)  0/18 (0.00%)  0/9 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-1873
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02024932     History of Changes
Other Study ID Numbers: CBVS857X2202
First Submitted: December 29, 2013
First Posted: December 31, 2013
Results First Submitted: April 12, 2017
Results First Posted: August 11, 2017
Last Update Posted: August 18, 2017