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

• ClinicalTrials.gov Identifier: NCT02024932
• Recruitment Status: Completed
• First Posted: December 31, 2013
• Results First Posted: August 11, 2017
• Last Update Posted: January 5, 2021
• Sponsor: Novartis Pharmaceuticals
• 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

Participant Flow

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)
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

Baseline Characteristics

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
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
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

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability
Description	Safety was monitored throughout the study.
Time Frame	After 78 days in Part A and after 85 days in Part B.

Outcome Measure Data

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)
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
Description	Safety was monitored throughout the study.
Time Frame	After 78 days in Part A and after 85 days in Part B.

Outcome Measure Data

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)
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
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

Outcome Measure Data

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)
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)

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 (legacy)
	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
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

Outcome Measure Data

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)
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
Description	LBM was assessed by dual-energy X-ray (DXA) absorptiometry. A positive change from baseline indicate improvement.
Time Frame	Baseline, Day 85

Outcome Measure Data

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)
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
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

Outcome Measure Data

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)
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
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

Outcome Measure Data

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)
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
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

Outcome Measure Data

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)
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
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

Outcome Measure Data

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)
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
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

Outcome Measure Data

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)
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
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

Outcome Measure Data

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)
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
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

Outcome Measure Data

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)
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
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

Outcome Measure Data

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)
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
Description	Serum samples were obtained for PK assessment.
Time Frame	Days 1: pre-dose, 1, 4, 24, 48 hours post-dose

Outcome Measure Data

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)
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
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.

Outcome Measure Data

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)
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
Description	Serum samples were obtained for PK assessment.
Time Frame	Days 1: pre-dose, 1, 4, 24, 48 hours post-dose

Outcome Measure Data

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)
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
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.

Outcome Measure Data

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)
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
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.

Outcome Measure Data

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)
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
Description	Serum samples were obtained for the PK assessment.
Time Frame	Days 1: pre-dose, 1, 4, 24, 48 hours post-dose

Outcome Measure Data

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)
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
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.

Outcome Measure Data

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)
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)
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.

Outcome Measure Data

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)
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)
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.

Outcome Measure Data

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)
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)
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.

Outcome Measure Data

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)
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
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.

Outcome Measure Data

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)
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.

Adverse Events

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)
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	--/--	--/--	--/--	--/--	--/--	--/--
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%)
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)

Limitations and Caveats

[Not Specified]

More Information

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Grunseich C, Miller R, Swan T, Glass DJ, El Mouelhi M, Fornaro M, Petricoul O, Vostiar I, Roubenoff R, Meriggioli MN, Kokkinis A, Guber RD, Budron MS, Vissing J, Soraru G, Mozaffar T, Ludolph A, Kissel JT, Fischbeck KH; BVS857 study group. Safety, tolerability, and preliminary efficacy of an IGF-1 mimetic in patients with spinal and bulbar muscular atrophy: a randomised, placebo-controlled trial. Lancet Neurol. 2018 Dec;17(12):1043-1052. doi: 10.1016/S1474-4422(18)30320-X. Epub 2018 Oct 15.

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT02024932
• 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: January 5, 2021