Atacicept in Multiple Sclerosis Extension Study, Phase II (ATAMS ext)

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First/last participant (informed consent): 03 March 2009/13 August 2009. Last participant completed: 09 September 2009.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups

	Description
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.

Participant Flow:   Overall Study

	Atacicept 25 mg (With Loading)	Atacicept 75 mg (With Loading)	Atacicept 150 mg (With Loading)	Atacicept 150 mg (Without Loading)
STARTED	16	19	17	22
COMPLETED	0	0	0	0
NOT COMPLETED	16	19	17	22
Premature Termination	16	15	14	21
Protocol Violation	0	0	0	1
Withdrawal by Subject	0	0	1	0
Unspecified	0	2	0	0
Randomised but not Treated	0	2	2	0

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population included all randomized subjects.

Reporting Groups

	Description
Atacicept 25 mg (With Loading)	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)	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.
Total	Total of all reporting groups

Baseline Measures

	Atacicept 25 mg (With Loading)	Atacicept 75 mg (With Loading)	Atacicept 150 mg (With Loading)	Atacicept 150 mg (Without Loading)	Total
Overall Participants Analyzed  [Units: Participants]	16	19	17	22	74
Age  [Units: Years] Mean (Standard Deviation)	39.4  (8.4)	36.8  (9.1)	37.4  (11.2)	34.4  (8.6)	36.8  (9.3)
Sex: Female, Male  [Units: Participants] Count of Participants
Female	8  50.0%	12  63.2%	8  47.1%	16  72.7%	44  59.5%
Male	8  50.0%	7  36.8%	9  52.9%	6  27.3%	30  40.5%

1.  Primary:

Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Injection Site Reactions, Infections, and Malignancies by Severity   [ Time Frame: From the first dose of study drug administration up to Week 24 ]

2.  Primary:

Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)   [ Time Frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36 ]

3.  Primary:

Change From Baseline in Vital Signs: Pulse Rate   [ Time Frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36 ]

4.  Primary:

Change From Baseline in Vital Signs: Temperature   [ Time Frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24 and 36 ]

5.  Primary:

Change From Baseline in Electrocardiogram (ECGs)   [ Time Frame: Baseline, Week 12 and 36 ]

6.  Primary:

Number of Subjects With Worsened Post Baseline Shift in Immunoglobulin A (IgA), IgG and IgM Levels   [ Time Frame: Baseline up to Week 36 ]

7.  Primary:

Number of Subjects With Positive Neutralizing Antibody (NAb)   [ Time Frame: Baseline, Week 12 and 36 ]

8.  Secondary:

Number of Subjects With Clinical Attacks/Relapses   [ Time Frame: Baseline up to Week 24 ]

9.  Secondary:

Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Week 12   [ Time Frame: Baseline, Week 12 ]

10.  Secondary:

Change in Multiple Sclerosis Functional Composite (MSFC) Score at Week 12   [ Time Frame: Week 12 ]

11.  Secondary:

Magnetic Resonance Imaging (MRI) Parameters: Number of T1 Gadolinium (Gd)-Enhancing Lesions Per Subject   [ Time Frame: Baseline, Week 12 and 24 ]

12.  Secondary:

Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions (New or Enlarging T2 Lesions) Per Subject   [ Time Frame: Baseline, Week 12 and Week 24 ]

13.  Secondary:

Concentrations of Free and Total Atacicept   [ Time Frame: Baseline and Week 12 ]

14.  Secondary:

Free B-Lymphocyte Stimulator (BLyS) and Free A Proliferation-Inducing Ligand (APRIL) Serum Concentrations.   [ Time Frame: Baseline, Week 12 and 36 ]

15.  Secondary:

Pharmacogenetics/Pharmacogenomics Analysis   [ Time Frame: Day 1 and Week 36 ]

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Sponsor voluntarily decided to terminate this trial after observing increased MS disease activity in trial 28063 ATAMS.