Trial Outcomes & Findings for Atacicept in Multiple Sclerosis Extension Study, Phase II (NCT NCT00853762)

Last Updated: 2017-03-20

Results Overview

TEAEs were defined as AEs with a start date after or on the date of the first DB treatment injection in ATAMS Extension and that occurred anytime after treatment discontinuation, or up to the day before first Rebif® rescue medication injection in ATAMS Extension. A serious TEAE was an AE that resulted in any of the following: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE severity was graded as per Qualitative Toxicity Scale. Local injection site reactions (injection site: pain, redness, itching and swelling) throughout ATAMS Extension, starting after the first trial medication administration. If the subject experienced 1 or more of the above injection site symptoms, these were reported with the AE verbatim term "injection site reaction". For all randomized subjects, there was an option of rescue treatment with Rebif® for 1 year beginning with the first injection of Rebif®).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

74 participants

Primary outcome timeframe

From the first dose of study drug administration up to Week 24

Results posted on

2017-03-20

Participant Flow

First/last participant (informed consent): 03 March 2009/13 August 2009. Last participant completed: 09 September 2009.

A total of 324 subjects were screened and 255 were enrolled in ATAMS (28063; NCT00642902). Overall, 75 subjects randomized and treated in ATAMS were eligible to enter ATAMS Extension. However, 74 subjects were included in ATAMS Extension and 1 subject could not enter due to the premature termination of the trial.

Participant milestones

Participant milestones
Measure	Atacicept 25 mg (With Loading) Subjects who received atacicept 25 milligram (mg) subcutaneously (SC) as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study were continued with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 75 mg (With Loading) Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study were continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (With Loading) Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study were continued with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (Without Loading) Subjects who received placebo SC twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study were continued with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
Overall Study STARTED	16	19	17	22
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	16	19	17	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Atacicept 25 mg (With Loading) Subjects who received atacicept 25 milligram (mg) subcutaneously (SC) as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study were continued with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 75 mg (With Loading) Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study were continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (With Loading) Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study were continued with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (Without Loading) Subjects who received placebo SC twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study were continued with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
Overall Study Premature Termination	16	15	14	21
Overall Study Protocol Violation	0	0	0	1
Overall Study Withdrawal by Subject	0	0	1	0
Overall Study Other	0	2	0	0
Overall Study Randomised but not Treated	0	2	2	0

Baseline Characteristics

Atacicept in Multiple Sclerosis Extension Study, Phase II

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Atacicept 25 mg (With Loading) n=16 Participants Subjects who received atacicept 25 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study were continued with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 75 mg (With Loading) n=19 Participants Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study were continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (With Loading) n=17 Participants Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study were continued with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (Without Loading) n=22 Participants Subjects who received placebo SC twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study were continued with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Total n=74 Participants Total of all reporting groups
Age, Continuous	39.4 years STANDARD_DEVIATION 8.4 • n=5 Participants	36.8 years STANDARD_DEVIATION 9.1 • n=7 Participants	37.4 years STANDARD_DEVIATION 11.2 • n=5 Participants	34.4 years STANDARD_DEVIATION 8.6 • n=4 Participants	36.8 years STANDARD_DEVIATION 9.3 • n=21 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	12 Participants n=7 Participants	8 Participants n=5 Participants	16 Participants n=4 Participants	44 Participants n=21 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants	6 Participants n=4 Participants	30 Participants n=21 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug administration up to Week 24

Population: Double-blind safety analysis set included all the subjects who received at least 1 dose of trial medication in the ATAMS extension study.

Outcome measures

Outcome measures
Measure	Atacicept 150 mg (Without Loading) n=22 Participants Subjects who received placebo SC twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study were continued with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 25 mg (With Loading) n=16 Participants Subjects who received atacicept 25 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study were continued with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 75 mg (With Loading) n=17 Participants Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study were continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (With Loading) n=15 Participants Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study were continued with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity Mild TEAEs	13 Subjects	5 Subjects	8 Subjects	8 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity Moderate TEAEs	4 Subjects	2 Subjects	4 Subjects	6 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity Severe TEAEs	1 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity Mild serious TEAEs	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity Moderate serious TEAEs	0 Subjects	0 Subjects	1 Subjects	0 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity Severe serious TEAEs	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity Mild injection site reaction	5 Subjects	2 Subjects	2 Subjects	5 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity Moderate injection site reaction	2 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity Severe injection site reaction	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity Mild infections	6 Subjects	1 Subjects	2 Subjects	4 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity Moderate infections	0 Subjects	0 Subjects	1 Subjects	2 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity Severe infections	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity Mild malignancies	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity Moderate malignancies	0 Subjects	1 Subjects	0 Subjects	0 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity Severe malignancies	0 Subjects	0 Subjects	0 Subjects	0 Subjects

PRIMARY outcome

Timeframe: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36

Population: Double-blind safety analysis set included all the subjects who received at least 1 dose of trial medication in the ATAMS extension study. Here 'n' signifies those subjects who were evaluable for the specified category.

Blood pressure (systolic and diastolic) was measured after at least 3 minutes resting, with the subject in the seated position.

Outcome measures

PRIMARY outcome

Timeframe: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36

Outcome measures

Outcome measures
Measure	Atacicept 150 mg (Without Loading) n=22 Participants Subjects who received placebo SC twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study were continued with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 25 mg (With Loading) n=16 Participants Subjects who received atacicept 25 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study were continued with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 75 mg (With Loading) n=17 Participants Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study were continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (With Loading) n=15 Participants Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study were continued with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
Change From Baseline in Vital Signs: Pulse Rate Week 8 (n=13, 11, 12, 16)	4.4 beats per minute (beats/min) Standard Deviation 12.4	-1.7 beats per minute (beats/min) Standard Deviation 9.2	-3.4 beats per minute (beats/min) Standard Deviation 9.1	1.3 beats per minute (beats/min) Standard Deviation 8.7
Change From Baseline in Vital Signs: Pulse Rate Week 2 (n=15, 13, 14, 21)	3.6 beats per minute (beats/min) Standard Deviation 11.4	-2.1 beats per minute (beats/min) Standard Deviation 5.1	-3.5 beats per minute (beats/min) Standard Deviation 5.5	-3.8 beats per minute (beats/min) Standard Deviation 10.4
Change From Baseline in Vital Signs: Pulse Rate Week 4 (n=15, 14, 12, 21)	2.0 beats per minute (beats/min) Standard Deviation 8.0	0.6 beats per minute (beats/min) Standard Deviation 8.7	-0.6 beats per minute (beats/min) Standard Deviation 9.2	0.7 beats per minute (beats/min) Standard Deviation 8.2
Change From Baseline in Vital Signs: Pulse Rate Week 12 (n=11, 12, 8, 16)	4.5 beats per minute (beats/min) Standard Deviation 9.5	-0.5 beats per minute (beats/min) Standard Deviation 6.2	0.7 beats per minute (beats/min) Standard Deviation 9.5	-1.5 beats per minute (beats/min) Standard Deviation 8.9
Change From Baseline in Vital Signs: Pulse Rate Week 16 (n=7, 9, 6, 12)	3.8 beats per minute (beats/min) Standard Deviation 9.1	3.9 beats per minute (beats/min) Standard Deviation 4.7	1.1 beats per minute (beats/min) Standard Deviation 10.5	-0.2 beats per minute (beats/min) Standard Deviation 4.8
Change From Baseline in Vital Signs: Pulse Rate Week 20 (n=3, 7, 2, 6)	11.0 beats per minute (beats/min) Standard Deviation 8.8	-0.3 beats per minute (beats/min) Standard Deviation 2.1	3.9 beats per minute (beats/min) Standard Deviation 8.3	-5.0 beats per minute (beats/min) Standard Deviation 9.9
Change From Baseline in Vital Signs: Pulse Rate Week 24 (n=2, 4, 1, 6)	9.0 beats per minute (beats/min) Standard Deviation 5.3	2.5 beats per minute (beats/min) Standard Deviation 0.7	-5.3 beats per minute (beats/min) Standard Deviation 9.4	-22.0 beats per minute (beats/min) Standard Deviation NA Standard deviation is not applicable as only 1 subject was evaluable for this parameter
Change From Baseline in Vital Signs: Pulse Rate Week 36 (n=0, 1, 0, 0)	NA beats per minute (beats/min) Standard Deviation NA The number of subjects evaluable was zero. Hence, data is not available.	NA beats per minute (beats/min) Standard Deviation NA The number of subjects evaluable was zero. Hence, data is not available.	7.0 beats per minute (beats/min) Standard Deviation NA Standard deviation is not applicable as only 1 subject was evaluable for this parameter	NA beats per minute (beats/min) Standard Deviation NA The number of subjects evaluable was zero. Hence, data is not available.

PRIMARY outcome

Timeframe: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36

Outcome measures

Outcome measures
Measure	Atacicept 150 mg (Without Loading) n=22 Participants Subjects who received placebo SC twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study were continued with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 25 mg (With Loading) n=16 Participants Subjects who received atacicept 25 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study were continued with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 75 mg (With Loading) n=17 Participants Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study were continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (With Loading) n=15 Participants Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study were continued with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
Change From Baseline in Vital Signs: Temperature Week 16 (n=7, 9, 6, 12)	0.01 Degree Celsius Standard Deviation 0.42	-0.10 Degree Celsius Standard Deviation 0.21	0.17 Degree Celsius Standard Deviation 0.35	-0.05 Degree Celsius Standard Deviation 0.23
Change From Baseline in Vital Signs: Temperature Week 2 (n=15, 13, 14, 21)	-0.07 Degree Celsius Standard Deviation 0.36	-0.09 Degree Celsius Standard Deviation 0.27	0.09 Degree Celsius Standard Deviation 0.27	0.03 Degree Celsius Standard Deviation 0.21
Change From Baseline in Vital Signs: Temperature Week 4 (n=15, 14, 12, 21)	-0.12 Degree Celsius Standard Deviation 0.31	-0.03 Degree Celsius Standard Deviation 0.24	0.05 Degree Celsius Standard Deviation 0.42	0.03 Degree Celsius Standard Deviation 0.24
Change From Baseline in Vital Signs: Temperature Week 8 (n=13, 11, 12, 16)	-0.14 Degree Celsius Standard Deviation 0.25	-0.03 Degree Celsius Standard Deviation 0.40	0.05 Degree Celsius Standard Deviation 0.10	0.03 Degree Celsius Standard Deviation 0.28
Change From Baseline in Vital Signs: Temperature Week 12 (n=11, 12, 8, 16)	-0.15 Degree Celsius Standard Deviation 0.34	0.02 Degree Celsius Standard Deviation 0.19	0.08 Degree Celsius Standard Deviation 0.36	0.09 Degree Celsius Standard Deviation 0.57
Change From Baseline in Vital Signs: Temperature Week 20 (n=3, 7, 2, 6)	-0.08 Degree Celsius Standard Deviation 0.45	-0.37 Degree Celsius Standard Deviation 0.35	0.16 Degree Celsius Standard Deviation 0.56	-0.25 Degree Celsius Standard Deviation 0.07
Change From Baseline in Vital Signs: Temperature Week 24 (n=2, 4, 1, 6)	-0.07 Degree Celsius Standard Deviation 0.26	0.05 Degree Celsius Standard Deviation 0.07	0.30 Degree Celsius Standard Deviation 0.59	0.00 Degree Celsius Standard Deviation NA Standard deviation is not applicable as only 1 subject was evaluable for this parameter.
Change From Baseline in Vital Signs: Temperature Week 36 (n=0, 1, 0, 0)	NA Degree Celsius Standard Deviation NA The number of subjects evaluable was zero. Hence, data is not available.	NA Degree Celsius Standard Deviation NA The number of subjects evaluable was zero. Hence, data is not available.	0.70 Degree Celsius Standard Deviation NA Standard deviation is not applicable as only 1 subject was evaluable for this parameter.	NA Degree Celsius Standard Deviation NA The number of subjects evaluable was zero. Hence, data is not available.

PRIMARY outcome

Timeframe: Baseline, Week 12 and 36

Population: No summary tables were prepared for ECG parameters, and ECG data were not formally analyzed. However, a qualitative assessment of ECG morphology and rhythm was made by the Investigator and recorded in the electronic case report form (eCRF). ECG abnormalities considered significant by the investigator were reported as AEs.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline up to Week 36

Population: Intent-to-treat (ITT) population included all randomized subjects.

Number of subjects with shifts from normal Grade (Grade 0) at Baseline to worse value at post-baseline (Grade 1 to Grade 4) according to the following criteria: IgA Grade 0: greater than or equal to (\>=) lower limit normal (LLN) 0.7 gram per liter (g/L); Grade 1: less than (\<) LLN - 0.5 g/L, Grade 2: \<0.5g/L -0.3 g/L, Grade 3: \<0.3 g/L -0.1 g/L, Grade 4: \< 0.1 g/L; IgG Grade 0: \>= LLN (7 g/L), Grade 1: \< LLN - 5 g/L, Grade 2: \<5g/L -4 g/L, Grade 3: \<4 g/L -3 g/L and Grade 4: \< 3 g/L; IgM Grade 0: \>= LLN (0.4 g/L), Grade 1: \< LLN - 0.3 g/L, Grade 2: \<0.3 g/L -0.2 g/L, Grade 3: \<0.2 g/L -0.1 g/L, and Grade 4: \< 0.1 g/L are presented in this outcome measure.

Outcome measures

Outcome measures
Measure	Atacicept 150 mg (Without Loading) n=22 Participants Subjects who received placebo SC twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study were continued with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 25 mg (With Loading) n=16 Participants Subjects who received atacicept 25 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study were continued with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 75 mg (With Loading) n=19 Participants Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study were continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (With Loading) n=17 Participants Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study were continued with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels IgA	9 Subjects	1 Subjects	3 Subjects	10 Subjects
Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels IgG	5 Subjects	4 Subjects	8 Subjects	12 Subjects
Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels IgM	7 Subjects	7 Subjects	6 Subjects	14 Subjects

PRIMARY outcome

Timeframe: Baseline, Week 12 and 36

Population: Appropriate method/test was not established to identify the positive neutralizing antibodies for atacicept. Hence, this outcome measure was not assessed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: Intent-to-treat (ITT) population included all randomized subjects.

A clinical attack/relapse was defined as the fulfillment of all the following criteria: 1. Neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both i) neurological abnormality separated by at least 30 days from onset of a preceding clinical event, and ii) neurological abnormality lasting for at least 24 hours. 2. Absence of fever or known infection (fever with temperature (axillary, orally, or intra-auriculary) \> 37.5°C/99.5 °Fahrenheit). 3. Objective neurological impairment, correlating with the subject's reported symptoms, defined as either i) increase in at least 1 of the functional systems of the Expanded Disability Status Scale (EDSS), or ii) increase of the total EDSS score. EDSS overall score ranging from 0 (normal) to 10 (death due to MS) was calculated.

Outcome measures

Outcome measures
Measure	Atacicept 150 mg (Without Loading) n=22 Participants Subjects who received placebo SC twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study were continued with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 25 mg (With Loading) n=16 Participants Subjects who received atacicept 25 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study were continued with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 75 mg (With Loading) n=19 Participants Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study were continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (With Loading) n=17 Participants Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study were continued with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
Number of Subjects With Clinical Attacks/Relapses No Relapse	21 Subjects	16 Subjects	16 Subjects	15 Subjects
Number of Subjects With Clinical Attacks/Relapses 1 Relapse	1 Subjects	0 Subjects	3 Subjects	2 Subjects
Number of Subjects With Clinical Attacks/Relapses 2 Relapse	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Clinical Attacks/Relapses 3 Relapse	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Clinical Attacks/Relapses Greater than or equal to (>=) 4 Relapse	0 Subjects	0 Subjects	0 Subjects	0 Subjects

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Intent-to-treat (ITT) population included all randomized subjects. "N" signifies (total number of subjects analyzed) the number of evaluable subjects for this outcome measure.

EDSS is an ordinal scale in half-point increments that qualifies disability in participants with multiple sclerosis (MS). It assesses the 8 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder, cerebral and other) as well as ambulation. EDSS overall score ranging from 0 (normal) to 10 (death due to MS) was calculated.

Outcome measures

Outcome measures
Measure	Atacicept 150 mg (Without Loading) n=16 Participants Subjects who received placebo SC twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study were continued with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 25 mg (With Loading) n=11 Participants Subjects who received atacicept 25 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study were continued with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 75 mg (With Loading) n=13 Participants Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study were continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (With Loading) n=10 Participants Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study were continued with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Week 12	-0.06 Units on a scale Standard Deviation 0.75	0.09 Units on a scale Standard Deviation 0.58	0.04 Units on a scale Standard Deviation 0.97	0.50 Units on a scale Standard Deviation 0.85

SECONDARY outcome

Timeframe: Week 12

Population: Intent-to-treat (ITT) population included all randomized subjects. "N" signifies number of evaluable subjects for this outcome measure.

The MSFC is a multidimensional clinical outcome measure which consists of three sub-tests; Timed 25-Foot Walk, 9-Hole Peg Test and Paced Auditory Serial Addition Test-3(PASAT-3). The Timed 25-Foot Walk is a quantitative measure of lower extremity function. The 9-Hole Peg Test is a quantitative measure of upper extremity (arm and hand) function. The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Standardized results (Z-scores) of these sub-tests and the overall MSFC Z-score as an average of these three Z-scores was calculated. Higher Z-scores reflect better neurological function and a positive change from baseline indicates improvement. An increase in score indicates an improvement (range -3 to +3).

Outcome measures

Outcome measures
Measure	Atacicept 150 mg (Without Loading) n=16 Participants Subjects who received placebo SC twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study were continued with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 25 mg (With Loading) n=11 Participants Subjects who received atacicept 25 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study were continued with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 75 mg (With Loading) n=13 Participants Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study were continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (With Loading) n=9 Participants Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study were continued with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
Change in Multiple Sclerosis Functional Composite (MSFC) Score at Week 12	0.07 z-score Standard Deviation 0.34	0.21 z-score Standard Deviation 0.40	0.04 z-score Standard Deviation 0.47	-0.01 z-score Standard Deviation 0.24

SECONDARY outcome

Timeframe: Baseline, Week 12 and 24

Population: Intent-to-treat (ITT) population included all randomized subjects. "n" signifies the number of evaluable subjects for this outcome measure.

Outcome measures

Outcome measures
Measure	Atacicept 150 mg (Without Loading) n=22 Participants Subjects who received placebo SC twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study were continued with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 25 mg (With Loading) n=16 Participants Subjects who received atacicept 25 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study were continued with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 75 mg (With Loading) n=19 Participants Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study were continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (With Loading) n=17 Participants Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study were continued with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject Baseline (n=16, 19, 17, 22)	0.9 Number of lesions per subject Standard Deviation 1.4	1.1 Number of lesions per subject Standard Deviation 2.2	2.3 Number of lesions per subject Standard Deviation 5.0	0.8 Number of lesions per subject Standard Deviation 1.4
Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject Week 12 (n=11, 11, 7, 15)	2.27 Number of lesions per subject Standard Deviation 7.16	0.27 Number of lesions per subject Standard Deviation 0.47	0.64 Number of lesions per subject Standard Deviation 1.29	1.00 Number of lesions per subject Standard Deviation 1.15
Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject Week 24 (n=2, 3, 1, 6)	0.83 Number of lesions per subject Standard Deviation 0.75	0.00 Number of lesions per subject Standard Deviation 0.00	2.00 Number of lesions per subject Standard Deviation 2.00	0.00 Number of lesions per subject Standard Deviation 0.00

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Outcome measures

Outcome measures
Measure	Atacicept 150 mg (Without Loading) n=22 Participants Subjects who received placebo SC twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study were continued with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 25 mg (With Loading) n=16 Participants Subjects who received atacicept 25 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study were continued with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 75 mg (With Loading) n=19 Participants Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study were continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (With Loading) n=17 Participants Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study were continued with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject Week 12 (n=11, 11, 7, 15)	5365.63 Cubic millimeter Standard Deviation 7445.87	5604.42 Cubic millimeter Standard Deviation 5154.52	7634.89 Cubic millimeter Standard Deviation 6340.19	4934.03 Cubic millimeter Standard Deviation 4802.98
Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject Week 24 (n=2, 3, 1, 6)	5541.80 Cubic millimeter Standard Deviation 5614.73	1699.60 Cubic millimeter Standard Deviation 586.76	6814.60 Cubic millimeter Standard Deviation 6643.00	1931.40 Cubic millimeter Standard Deviation 0.00
Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject Baseline (n=16, 19, 17, 22)	5868.84 Cubic millimeter Standard Deviation 7170.81	4792.76 Cubic millimeter Standard Deviation 3152.56	8196.59 Cubic millimeter Standard Deviation 8888.74	6158.04 Cubic millimeter Standard Deviation 7945.59

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: This outcome measure was not assessed due to lack of a valid assay during the usable time period of the samples.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 12 and 36

Population: This outcome measure was not assessed due to lack of a valid assay for measuring BLyS and APRIL.

Levels of free APRIL and free BLyS: Free APRIL serum samples were to be analyzed by using a validated enzyme-linked immunosorbent assay (ELISA) with limits of detection of 0.3125 nanogram per milliliter (ng/mL) for free APRIL and free BlyS serum samples were analysed using a validated ELISA with limits of detection of 1.56 ng/mL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 and Week 36

Population: Genetic/genomic analysis was not performed as the trial was terminated early.

Gene expression profiling and gene polymorphism identification were to be used to identify putative markers for response to treatment. * Genome-wide gene polymorphism characterization by genome-wide scan. * Targeted gene polymorphism identification of B-Lymphocyte Stimulator (BLyS) , APRIL, (receptor for B cell activating factor of the tumor necrosis factor \[TNF\] family) BAFF-R, (Transmembrane Activator) TACI and (B Cell Maturation Antigen) BCMA and HLA-DRB1 by direct genotyping or sequencing .

Outcome measures

Outcome data not reported

Adverse Events

Atacicept 25 mg (With Loading)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Atacicept 75 mg (With Loading)

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Atacicept 150 mg (With Loading)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Atacicept 150 mg (Without Loading)

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Atacicept 25 mg (With Loading) n=16 participants at risk Subjects who received atacicept 25 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study were continued with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 75 mg (With Loading) n=17 participants at risk Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study were continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (With Loading) n=15 participants at risk Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study were continued with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (Without Loading) n=22 participants at risk Subjects who received placebo SC as loading dose twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study were continued with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
General disorders Peripheral Edema	0.00% 0/16 • From the first dose of study drug administration up to Week 24 AEs were collected for Double-blind safety analysis set which included all the subjects who received at least 1 dose of trial medication in the ATAMS extension study.	5.9% 1/17 • From the first dose of study drug administration up to Week 24 AEs were collected for Double-blind safety analysis set which included all the subjects who received at least 1 dose of trial medication in the ATAMS extension study.	0.00% 0/15 • From the first dose of study drug administration up to Week 24 AEs were collected for Double-blind safety analysis set which included all the subjects who received at least 1 dose of trial medication in the ATAMS extension study.	0.00% 0/22 • From the first dose of study drug administration up to Week 24 AEs were collected for Double-blind safety analysis set which included all the subjects who received at least 1 dose of trial medication in the ATAMS extension study.

Other adverse events

Additional Information

Merck KGaA Communication Center

Merck Serono, a division of Merck KGaA

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The study as a whole will be published prior to any individual investigator publications. It is required that copies of all papers, abstracts, articles, etc. that contain study data are to be forward to the Sponsor for review 30 days prior to submission for publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Atacicept 150 mg (Without Loading) n=22 Participants Subjects who received placebo SC twice weekly for first 4 weeks, followed by placebo SC for 32 weeks, in 28063 study were continued with atacicept 150 mg (without loading dose) SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 25 mg (With Loading) n=16 Participants Subjects who received atacicept 25 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 25 mg SC for 32 weeks, in 28063 study were continued with atacicept 25 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 75 mg (With Loading) n=17 Participants Subjects who received atacicept 75 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 75 mg SC for 32 weeks, in 28063 study were continued with atacicept 75 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.	Atacicept 150 mg (With Loading) n=15 Participants Subjects who received atacicept 150 mg SC as loading dose twice weekly for first 4 weeks, followed by atacicept 150 mg SC for 32 weeks, in 28063 study were continued with atacicept 150 mg SC once weekly up to 5 years or up to early termination of treatment or early termination of the study.
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: Week 2 (n = 13, 16, 14, 20)	-0.2 millimeter of mercury (mmHg) Standard Deviation 9.8	2.6 millimeter of mercury (mmHg) Standard Deviation 8.3	-3.0 millimeter of mercury (mmHg) Standard Deviation 9.5	-1.2 millimeter of mercury (mmHg) Standard Deviation 10.7
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: Week 4 (n = 15, 14, 12, 21)	-0.1 millimeter of mercury (mmHg) Standard Deviation 9.9	2.1 millimeter of mercury (mmHg) Standard Deviation 7.9	-2.4 millimeter of mercury (mmHg) Standard Deviation 13.7	-5.1 millimeter of mercury (mmHg) Standard Deviation 12.6
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: Week 8 (n = 13, 11, 12, 16)	0.4 millimeter of mercury (mmHg) Standard Deviation 11.0	0.8 millimeter of mercury (mmHg) Standard Deviation 10.5	-2.1 millimeter of mercury (mmHg) Standard Deviation 12.0	-1.1 millimeter of mercury (mmHg) Standard Deviation 12.5
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: Week 12 (n = 11, 12, 8, 16)	-0.9 millimeter of mercury (mmHg) Standard Deviation 11.3	3.0 millimeter of mercury (mmHg) Standard Deviation 11.7	-5.8 millimeter of mercury (mmHg) Standard Deviation 15.3	-3.4 millimeter of mercury (mmHg) Standard Deviation 10.2
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: Week 16 (n=7, 9, 6, 12)	-2.3 millimeter of mercury (mmHg) Standard Deviation 10.0	5.9 millimeter of mercury (mmHg) Standard Deviation 13.4	-9.0 millimeter of mercury (mmHg) Standard Deviation 18.6	-2.0 millimeter of mercury (mmHg) Standard Deviation 12.2
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: Week 20 (n=3, 7, 2, 6)	3.3 millimeter of mercury (mmHg) Standard Deviation 6.0	2.0 millimeter of mercury (mmHg) Standard Deviation 23.1	-9.7 millimeter of mercury (mmHg) Standard Deviation 14.8	-0.5 millimeter of mercury (mmHg) Standard Deviation 0.7
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: Week 24 (n=2, 4, 1, 6)	-5.3 millimeter of mercury (mmHg) Standard Deviation 7.7	5.0 millimeter of mercury (mmHg) Standard Deviation 7.1	-5.0 millimeter of mercury (mmHg) Standard Deviation 4.1	10.0 millimeter of mercury (mmHg) Standard Deviation NA Standard deviation is not evaluable as only 1 subject was evaluated for this parameter.
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: Week 36 (n=0, 1, 0, 0)	NA millimeter of mercury (mmHg) Standard Deviation NA The number of subjects evaluated was zero. Hence, data is not available.	NA millimeter of mercury (mmHg) Standard Deviation NA The number of subjects evaluated was zero. Hence, data is not available.	-18.0 millimeter of mercury (mmHg) Standard Deviation NA Standard deviation is not evaluable as only 1 subject was evaluated for this parameter.	NA millimeter of mercury (mmHg) Standard Deviation NA The number of subjects evaluated was zero. Hence, data is not available.
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: Week 2 (n=15, 13, 14, 21)	0.3 millimeter of mercury (mmHg) Standard Deviation 8.6	-2.1 millimeter of mercury (mmHg) Standard Deviation 8.2	-1.9 millimeter of mercury (mmHg) Standard Deviation 8.4	-3.6 millimeter of mercury (mmHg) Standard Deviation 10.6
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: Week 4 (n=15, 14, 12, 21)	0.1 millimeter of mercury (mmHg) Standard Deviation 7.7	-0.5 millimeter of mercury (mmHg) Standard Deviation 9.0	-0.4 millimeter of mercury (mmHg) Standard Deviation 8.7	-5.1 millimeter of mercury (mmHg) Standard Deviation 9.2
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: Week 8 (n=13, 11, 12, 16)	0.1 millimeter of mercury (mmHg) Standard Deviation 11.0	-2.8 millimeter of mercury (mmHg) Standard Deviation 7.7	-1.6 millimeter of mercury (mmHg) Standard Deviation 8.7	-5.9 millimeter of mercury (mmHg) Standard Deviation 10.2
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: Week 12 (n=11, 12, 8, 16)	-2.4 millimeter of mercury (mmHg) Standard Deviation 10.3	-3.8 millimeter of mercury (mmHg) Standard Deviation 11.1	-4.8 millimeter of mercury (mmHg) Standard Deviation 8.1	-3.5 millimeter of mercury (mmHg) Standard Deviation 9.9
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: Week 16 (n=7, 9, 6, 12)	-1.6 millimeter of mercury (mmHg) Standard Deviation 7.7	-1.6 millimeter of mercury (mmHg) Standard Deviation 14.2	-2.9 millimeter of mercury (mmHg) Standard Deviation 9.0	-2.3 millimeter of mercury (mmHg) Standard Deviation 4.2
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: Week 20 (n=3, 7, 2, 6)	3.7 millimeter of mercury (mmHg) Standard Deviation 6.3	-2.0 millimeter of mercury (mmHg) Standard Deviation 17.1	-4.4 millimeter of mercury (mmHg) Standard Deviation 6.0	2.0 millimeter of mercury (mmHg) Standard Deviation 4.2
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: Week 24 (n=2, 4, 1, 6)	-1.0 millimeter of mercury (mmHg) Standard Deviation 9.8	0.0 millimeter of mercury (mmHg) Standard Deviation 0.0	-6.3 millimeter of mercury (mmHg) Standard Deviation 2.5	0.0 millimeter of mercury (mmHg) Standard Deviation NA Standard deviation is not evaluable as only 1 subject was evaluated for this parameter.
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: Week 36 (n=0, 1, 0, 0)	NA millimeter of mercury (mmHg) Standard Deviation NA The number of subjects evaluated was zero. Hence, data is not available.	NA millimeter of mercury (mmHg) Standard Deviation NA The number of subjects evaluated was zero. Hence, data is not available.	-8.0 millimeter of mercury (mmHg) Standard Deviation NA Standard deviation is not evaluable as only 1 subject was evaluated for this parameter.	NA millimeter of mercury (mmHg) Standard Deviation NA The number of subjects evaluated was zero. Hence, data is not available.