Atacicept in Subjects With Optic Neuritis

• Sponsor: EMD Serono (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00624468
• Collaborator: Merck KGaA, Darmstadt, Germany (Industry)
• Enrollment: 34
• Locations: 28
• Arms: 2
• Duration (Months): 31
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study was intended to evaluate the efficacy, safety and tolerability of atacicept compared to placebo and to explore the neuroprotective effect of atacicept as assessed by OCT in subjects with ON as CIS. The study was randomized. Study medication was administered via subcutaneous (under the skin) injections.

Condition or Disease	Intervention/Treatment	Phase
Optic Neuritis	Drug: Atacicept; Drug: Placebo matched to atacicept	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Two-arm, Randomized, Double-blind, Placebo-controlled, Multicenter Phase II Study to Evaluate Safety and Tolerability and to Explore the Neuroprotective Effect of Atacicept as Assessed by Optical Coherence Tomography (OCT) in Subjects With Optic Neuritis (ON) as Clinically Isolated Syndrome (CIS) Over a 36-week Treatment Course
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Atacicept	Drug: Atacicept; Atacicept will be administered subcutaneously at a dose of 150 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
Placebo Comparator: Placebo	Drug: Placebo matched to atacicept; Placebo matched to atacicept will be administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Last Observed Value (LOV) [Baseline, LOV (Week 48)]

   The RNFL thickness was measured for 12 sectors (every 30 degrees) per eye in triplicate by optical coherence tomography (OCT) measurements and were then averaged over 12 sectors. The change in RNFL thickness at LOV visit was calculated as RNFL thickness at LOV minus RNFL thickness at baseline.

Secondary Outcome Measures

1. Difference in Retinal Nerve Fibre Layer (RNFL) Thickness Between the Affected Eye and Fellow Eye [Weeks 12, 24 and 36]

   The RNFL thickness was measured for 12 sectors (every 30 degrees) per eye in triplicate by optical coherence tomography (OCT) measurements and was then averaged over 12 sectors. Difference was calculated as RNFL thickness in affected eye minus RNFL thickness in fellow eye.

2. Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Weeks 12 and 24 [Baseline, Weeks 12 and 24]

   The RNFL thickness was measured for 12 sectors (every 30 degrees) per eye in triplicate by OCT measurements and was then averaged over 12 sectors. The change in RNFL thickness at Weeks 12 and 24 was calculated as RNFL thickness at Weeks 12 and 24 minus RNFL thickness at baseline, respectively.

3. Change From Baseline in Macular Thickness at 3 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 [Baseline, Weeks 12, 24 and 36]

   The change in macular thickness at 3 mm around fovea in the affected eye at Weeks 12, 24 and 36 was calculated as macular thickness at 3 mm in the affected eye at Weeks 12, 24 and 36 minus macular thickness at 3 mm in the affected eye at baseline, respectively.

4. Change From Baseline in Macular Thickness at 6 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 [Baseline, Weeks 12, 24 and 36]

   The change in macular thickness at 6 mm around fovea in the affected eye at Weeks 12, 24 and 36 was calculated as macular thickness at 6 mm in the affected eye at Weeks 12, 24 and 36 minus macular thickness at 6 mm in the affected eye at baseline, respectively.

5. Change From Baseline in Macular Volume in the Affected Eye at Weeks 12, 24 and 36 [Baseline, Weeks 12, 24 and 36]

   The change in macular volume in the affected eye at Weeks 12, 24 and 36 was calculated as macular volume in the affected eye at Weeks 12, 24 and 36 minus macular volume in the affected eye at baseline, respectively.

6. Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified [Weeks 12, 24 and 36]

   Low-contrast letter acuity was measured by using the Sloan Charts at 1.25 fraction (%) and 2.5%. Sloan letters are a set of optotypes used to test visual acuity. Total number of letters correctly identified in the affected and fellow eye were reported. The possible Sloan Chart range is 0 to 70. More the number of letters identified, better is the visual acuity.

7. Contrast Sensitivity: Total Number of Letters Correctly Identified [Weeks 12, 24 and 36]

   Contrast Sensitivity was measured using the Pelli-Robson Charts. Pelli-Robson chart is used for clinical measurement of contrast sensitivity and determines the contrast required to read large letters of a fixed size. Total number of letters correctly identified in the affected and fellow eye were reported. The total possible range is 0 to 48. More the number of letters identified, better is the contrast sensitivity.

8. Contrast Sensitivity: Score Line [Weeks 12, 24 and 36]

   Contrast sensitivity was measured using the Pelli-Robson charts with letters arranged in groups of 3. Pelli-Robson chart is used for clinical measurement of contrast sensitivity and determines the contrast required to read large letters of a fixed size. The possible score line range is 0 (visual disability) to 16 (normal contrast sensitivity).

9. Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) Second Clinical Attack [From baseline (Study Day 1) up to Week 36]

   Conversion to CDMS was defined as experiencing a second clinical attack meeting all of the following criteria: (a) 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; (b) Absence of fever or known infection (fever with temperature [axillary, orally or intraauricularly] greater than 37.5 degree Celsius/99.5 degree Fahrenheit); (c) Objective neurological impairment, correlating with the participant's reported symptoms, defined as either (i) Increase in at least 1 of the functional systems of the Expanded Disability Status Score (EDSS), or (ii) Increase of the total EDSS score. EDSS assesses disability in 8 functional systems and total score ranges from 0 (normal) to 10 (death due to MS). Percentage of participants converting to CDMS (second clinical attack) was reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of unilateral symptomatic optic neuritis as first clinical manifestation within 28 days between onset of symptoms and study Day 1

• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Pre treatment with immunosuppressants and immunomodulating drugs

• Relevant cardiac, hepatic and renal diseases

• Clinical significant abnormalities in blood cell counts and immunoglobulin levels

• Clinical significant acute or chronic infections

• Other protocol defined exclusion criteria could apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States
2	Research Site	Aurora	Colorado	United States
3	Research Site	Fairfield	Connecticut	United States
4	Research Site	Jacksonville	Florida	United States
5	Research Site	East Lansing	Michigan	United States
6	Research Site	Philadelphia	Pennsylvania	United States
7	Research Site	Houston	Texas	United States
8	Research Site	Burlington	Vermont	United States
9	Research Site	Parkville	Victoria	Australia
10	Research Site	Bruxelles		Belgium
11	Research Site	Vancouver	British Columbia	Canada
12	Research Site	Ottawa	Ontario	Canada
13	Research Site	Montreal	Quebec	Canada
14	Research Site	Hradec Kralove		Czech Republic
15	Research Site	Olomouc		Czech Republic
16	Research Site	Paris		France
17	Research Site	Freiburg		Germany
18	Research Site	Munich		Germany
19	Research Site	Tübingen		Germany
20	Research Site	Würzburg		Germany
21	Research Site	Beyrouth		Lebanon
22	Research Site	Dbayeh		Lebanon
23	Research Site	Barcelona		Spain
24	Research Site	Sevilla		Spain
25	Research Site	Valencia		Spain
26	Research Site	Lausanne		Switzerland
27	Research Site	London		United Kingdom
28	Research Site	Sheffield		United Kingdom

Sponsors and Collaborators

• EMD Serono
• Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible, EMD Serono, an affiliate of MerckKGaA, Darmstadt, Germany

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: EMD Serono
• ClinicalTrials.gov Identifier: NCT00624468
• Other Study ID Numbers: 28156
• First Posted: Feb 27, 2008
• Last Update Posted: Feb 17, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by EMD Serono: atacicept; neuritis
• Additional relevant MeSH terms: Neuritis; Optic Neuritis

Study Results

Participant Flow

Arm/Group Title	Placebo: Double-blind Period	Atacicept: Double-blind Period	Placebo: SFU Period	Atacicept: SFU Period
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.	Atacicept was administered subcutaneously at a dose of 150 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.	Subjects who received placebo matched to atacicept in double-blind period were included in safety follow-up (SFU) period (60 weeks) following premature termination of the trial.	Subjects who received atacicept in double-blind period were included in SFU period (60 weeks) following premature termination of the trial.
Period Title: Double-blind Period
STARTED	17	17	0	0
COMPLETED	3	4	0	0
NOT COMPLETED	14	13	0	0
Period Title: Double-blind Period
STARTED	0	0	13	14
COMPLETED	0	0	11	11
NOT COMPLETED	0	0	2	3

Baseline Characteristics

Arm/Group Title	Placebo: Double-blind Period	Atacicept: Double-blind Period	Total
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.	Atacicept was administered subcutaneously at a dose of 150 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.	Total of all reporting groups
Overall Participants	17	17	34
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.3 (7.1)	30.6 (10.2)	31.4 (8.7)
Sex: Female, Male (Count of Participants)
Female	14 82.4%	13 76.5%	27 79.4%
Male	3 17.6%	4 23.5%	7 20.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Last Observed Value (LOV)
Description	The RNFL thickness was measured for 12 sectors (every 30 degrees) per eye in triplicate by optical coherence tomography (OCT) measurements and were then averaged over 12 sectors. The change in RNFL thickness at LOV visit was calculated as RNFL thickness at LOV minus RNFL thickness at baseline.
Time Frame	Baseline, LOV (Week 48)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Here, "n" signifies those participants who were evaluable for the specified category.

Arm/Group Title	Placebo: Double-blind Period	Atacicept: Double-blind Period
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.	Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
Measure Participants	17	17
Baseline (n = 17, 17)	103.893 (17.271)	104.170 (8.832)
Change at LOV (n = 16, 15)	-17.317 (15.158)	-8.636 (10.056)

2. Secondary Outcome

Title	Difference in Retinal Nerve Fibre Layer (RNFL) Thickness Between the Affected Eye and Fellow Eye
Description	The RNFL thickness was measured for 12 sectors (every 30 degrees) per eye in triplicate by optical coherence tomography (OCT) measurements and was then averaged over 12 sectors. Difference was calculated as RNFL thickness in affected eye minus RNFL thickness in fellow eye.
Time Frame	Weeks 12, 24 and 36

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this outcome measure and "n" signifies those participants who were evaluable for the specified category.

Arm/Group Title	Placebo: Double-blind Period	Atacicept: Double-blind Period
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.	Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
Measure Participants	13	13
Change at Week 12 (n = 13, 13)	-14 (4)	-7.9 (1.5)
Change at Week 24 (n = 4, 5)	-7 (6.9)	-10.6 (3.7)
Change at Week 36 (n = 3, 4)	-7.5 (8.8)	-9.4 (6.6)

3. Secondary Outcome

Title	Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Weeks 12 and 24
Description	The RNFL thickness was measured for 12 sectors (every 30 degrees) per eye in triplicate by OCT measurements and was then averaged over 12 sectors. The change in RNFL thickness at Weeks 12 and 24 was calculated as RNFL thickness at Weeks 12 and 24 minus RNFL thickness at baseline, respectively.
Time Frame	Baseline, Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this outcome measure and "n" signifies those participants who were evaluable for the specified category.

Arm/Group Title	Placebo: Double-blind Period	Atacicept: Double-blind Period
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.	Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
Measure Participants	13	13
Baseline (n=17, 17)	103.893 (17.271)	104.170 (8.832)
Change at Week 12 (n = 13, 13)	-17.036 (13.919)	-9.356 (9.532)
Change at Week 24 (n = 4, 5)	-17.815 (16.505)	-11.234 (14.230)

4. Secondary Outcome

Title	Change From Baseline in Macular Thickness at 3 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36
Description	The change in macular thickness at 3 mm around fovea in the affected eye at Weeks 12, 24 and 36 was calculated as macular thickness at 3 mm in the affected eye at Weeks 12, 24 and 36 minus macular thickness at 3 mm in the affected eye at baseline, respectively.
Time Frame	Baseline, Weeks 12, 24 and 36

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Here, "n" signifies those participants who were evaluable for the specified category.

Arm/Group Title	Placebo: Double-blind Period	Atacicept: Double-blind Period
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.	Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
Measure Participants	17	17
Baseline (n = 17, 17)	1054.4 (76.5)	1070.6 (72.7)
Change at Week 12 (n = 13, 13)	-29.3 (34.4)	-34.0 (21.8)
Change at Week 24 (n = 4, 5)	-72.5 (47.0)	-50.4 (47.7)
Change at Week 36 (n = 3, 4)	-32.7 (30.7)	-40.0 (51.3)

5. Secondary Outcome

Title	Change From Baseline in Macular Thickness at 6 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36
Description	The change in macular thickness at 6 mm around fovea in the affected eye at Weeks 12, 24 and 36 was calculated as macular thickness at 6 mm in the affected eye at Weeks 12, 24 and 36 minus macular thickness at 6 mm in the affected eye at baseline, respectively.
Time Frame	Baseline, Weeks 12, 24 and 36

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Here, "n" signifies those participants who were evaluable for the specified category.

Arm/Group Title	Placebo: Double-blind Period	Atacicept: Double-blind Period
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.	Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
Measure Participants	17	17
Baseline (n = 17, 17)	954.4 (57.4)	947.5 (61.3)
Change at Week 12 (n = 13, 13)	-36.1 (28.4)	-32.8 (25.2)
Change at Week 24 (n = 4, 5)	-63.8 (32.7)	-46.2 (36.5)
Change at Week 36 (n = 3, 4)	-33.3 (33.7)	-34.8 (46.0)

6. Secondary Outcome

Title	Change From Baseline in Macular Volume in the Affected Eye at Weeks 12, 24 and 36
Description	The change in macular volume in the affected eye at Weeks 12, 24 and 36 was calculated as macular volume in the affected eye at Weeks 12, 24 and 36 minus macular volume in the affected eye at baseline, respectively.
Time Frame	Baseline, Weeks 12, 24 and 36

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Here, "n" signifies those participants who were evaluable for the specified category.

Arm/Group Title	Placebo: Double-blind Period	Atacicept: Double-blind Period
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.	Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
Measure Participants	17	17
Baseline (n = 17, 17)	6.8865 (0.4199)	6.8794 (0.4372)
Change at Week 12 (n = 13, 13)	-0.2389 (0.1991)	-0.2301 (0.1612)
Change at Week 24 (n = 4, 5)	-0.4630 (0.2466)	-0.3292 (0.2674)
Change at Week 36 (n = 3, 4)	-0.2353 (0.2253)	-0.2533 (0.3205)

7. Secondary Outcome

Title	Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified
Description	Low-contrast letter acuity was measured by using the Sloan Charts at 1.25 fraction (%) and 2.5%. Sloan letters are a set of optotypes used to test visual acuity. Total number of letters correctly identified in the affected and fellow eye were reported. The possible Sloan Chart range is 0 to 70. More the number of letters identified, better is the visual acuity.
Time Frame	Weeks 12, 24 and 36

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this outcome measure and "n" signifies those participants who were evaluable for the specified category.

Arm/Group Title	Placebo: Double-blind Period	Atacicept: Double-blind Period
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.	Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
Measure Participants	15	14
Sloan chart 1.25%, affected eye: Week 12 (n=15,14)	14.7 (14.7)	15.7 (19.0)
Sloan chart 1.25%, affected eye: Week 24 (n = 5,5)	16.2 (13.6)	13.4 (18.4)
Sloan chart 1.25%, affected eye: Week 36 (n = 3,4)	24.7 (8.1)	9.8 (18.8)
Sloan chart 2.5%, affected eye: Week 12 (n=15, 14)	25.6 (16.7)	22.1 (19.5)
Sloan chart 2.5%, affected eye: Week 24 (n = 5, 5)	26.8 (15.2)	21.4 (19.3)
Sloan chart 2.5%, affected eye: Week 36 (n = 3, 4)	38.7 (4.7)	20.3 (18.7)
Sloan chart 1.25%, fellow eye: Week 12 (n=15,14)	25.7 (13.1)	25.9 (16.5)
Sloan chart 1.25%, fellow eye: Week 24 (n = 5,5)	22.2 (16.1)	24.6 (18.4)
Sloan chart 1.25%, fellow eye: Week 36 (n = 3,4)	35.3 (4.2)	19.8 (20.6)
Sloan chart 2.5%, fellow eye: Week 12 (n=15, 14)	35.3 (13.4)	36.4 (12.7)
Sloan chart 2.5%, fellow eye: Week 24 (n = 5, 5)	33.6 (18.2)	35.8 (15.4)
Sloan chart 2.5%, fellow eye: Week 36 (n = 3, 4)	45.7 (4.5)	32.5 (19.1)

8. Secondary Outcome

Title	Contrast Sensitivity: Total Number of Letters Correctly Identified
Description	Contrast Sensitivity was measured using the Pelli-Robson Charts. Pelli-Robson chart is used for clinical measurement of contrast sensitivity and determines the contrast required to read large letters of a fixed size. Total number of letters correctly identified in the affected and fellow eye were reported. The total possible range is 0 to 48. More the number of letters identified, better is the contrast sensitivity.
Time Frame	Weeks 12, 24 and 36

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this outcome measure and "n" signifies those participants who were evaluable for the specified category.

Arm/Group Title	Placebo: Double-blind Period	Atacicept: Double-blind Period
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.	Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
Measure Participants	15	14
Affected eye: Week 12 (n = 15, 14)	35.4 (5.9)	32.4 (8.8)
Affected eye: Week 24 (n = 5, 5)	34.2 (6.9)	33.0 (4.7)
Affected eye: Week 36 (n = 3, 3)	37.0 (5.3)	34.7 (3.2)
Fellow eye: Week 12 (n = 15, 14)	38.3 (4.1)	37.6 (3.3)
Fellow eye: Week 24 (n = 5, 5)	36.2 (9.4)	37.4 (2.4)
Fellow eye: Week 36 (n = 3, 3)	39.7 (4.0)	40.0 (1.0)

9. Secondary Outcome

Title	Contrast Sensitivity: Score Line
Description	Contrast sensitivity was measured using the Pelli-Robson charts with letters arranged in groups of 3. Pelli-Robson chart is used for clinical measurement of contrast sensitivity and determines the contrast required to read large letters of a fixed size. The possible score line range is 0 (visual disability) to 16 (normal contrast sensitivity).
Time Frame	Weeks 12, 24 and 36

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this outcome measure and "n" signifies those participants who were evaluable for the specified category.

Arm/Group Title	Placebo: Double-blind Period	Atacicept: Double-blind Period
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.	Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
Measure Participants	15	14
Affected eye: Week 12 (n = 15, 14)	12.1 (1.5)	10.9 (2.9)
Affected eye: Week 24 (n = 5, 5)	11.4 (2.6)	11.2 (1.6)
Affected eye: Week 36 (n = 3, 3)	12.3 (2.1)	11.7 (1.5)
Fellow eye: Week 12 (n = 15, 14)	12.9 (1.5)	12.7 (1.1)
Fellow eye: Week 24 (n = 5, 5)	11.8 (3.3)	12.4 (0.5)
Fellow eye: Week 36 (n = 3, 3)	13.3 (1.2)	13.3 (0.6)

10. Secondary Outcome

Title	Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) Second Clinical Attack
Description	Conversion to CDMS was defined as experiencing a second clinical attack meeting all of the following criteria: (a) 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; (b) Absence of fever or known infection (fever with temperature [axillary, orally or intraauricularly] greater than 37.5 degree Celsius/99.5 degree Fahrenheit); (c) Objective neurological impairment, correlating with the participant's reported symptoms, defined as either (i) Increase in at least 1 of the functional systems of the Expanded Disability Status Score (EDSS), or (ii) Increase of the total EDSS score. EDSS assesses disability in 8 functional systems and total score ranges from 0 (normal) to 10 (death due to MS). Percentage of participants converting to CDMS (second clinical attack) was reported.
Time Frame	From baseline (Study Day 1) up to Week 36

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants.

Arm/Group Title	Placebo: Double-blind Period	Atacicept: Double-blind Period
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.	Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
Measure Participants	17	17
Number [percentage of participants]	17.6 103.5%	35.3 207.6%

Adverse Events

Time Frame	Baseline up to Week 48
Adverse Event Reporting Description	ITT population of the double-blind period included all randomized subjects according to their randomized treatment. SFU period population included all randomized participants of double-blind period who participated in the 60-week SFU (N=13,14 for Placebo and Atacicept arms respectively).
Arm/Group Title	Placebo: Double-blind Period		Atacicept: Double-blind Period		Placebo: SFU Period		Atacicept: SFU Period
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.		Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.		Participants who received placebo matched to atacicept in double-blind period were included in SFU period (60 weeks) following premature termination of the trial.		Participants who received atacicept in double-blind period were included in SFU period (60 weeks) following premature termination of the trial.
All Cause Mortality
	Placebo: Double-blind Period		Atacicept: Double-blind Period		Placebo: SFU Period		Atacicept: SFU Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo: Double-blind Period		Atacicept: Double-blind Period		Placebo: SFU Period		Atacicept: SFU Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		2/14 (14.3%)
General disorders
Pyrexia	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Infections and infestations
Bacterial pyelonephritis	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Nervous system disorders
Multiple sclerosis	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Myelitis transverse	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Myelitis	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Skin and subcutaneous tissue disorders
Blister	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Placebo: Double-blind Period		Atacicept: Double-blind Period		Placebo: SFU Period		Atacicept: SFU Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/17 (82.4%)		16/17 (94.1%)		6/13 (46.2%)		10/14 (71.4%)
Blood and lymphatic system disorders
Lymphadenopathy	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Anaemia of pregnancy	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Lymphopenia	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Cardiac disorders
Bundle branch block right	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Ventricular arrhythmia	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Ear and labyrinth disorders
Ear pain	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Vertigo	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Eye disorders
Eye pain	0/17 (0%)		2/17 (11.8%)		0/13 (0%)		1/14 (7.1%)
Asthenopia	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Eye haemorrhage	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Uhthoff's phenomenon	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Visual acuity reduced	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Photopsia	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Vitreous floaters	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Gastrointestinal disorders
Diarrhoea	3/17 (17.6%)		2/17 (11.8%)		0/13 (0%)		0/14 (0%)
Vomiting	2/17 (11.8%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Abdominal pain upper	0/17 (0%)		2/17 (11.8%)		0/13 (0%)		1/14 (7.1%)
Nausea	1/17 (5.9%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Abdominal pain	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Constipation	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		1/14 (7.1%)
Dyspepsia	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Tongue disorder	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Aerophagia	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Faecal incontinence	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Vomiting in pregnancy	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
General disorders
Injection site reaction	3/17 (17.6%)		11/17 (64.7%)		1/13 (7.7%)		2/14 (14.3%)
Fatigue	3/17 (17.6%)		3/17 (17.6%)		0/13 (0%)		0/14 (0%)
Injection site haematoma	1/17 (5.9%)		3/17 (17.6%)		0/13 (0%)		0/14 (0%)
Injection site erythema	1/17 (5.9%)		2/17 (11.8%)		0/13 (0%)		0/14 (0%)
Injection site pain	0/17 (0%)		2/17 (11.8%)		0/13 (0%)		0/14 (0%)
Asthenia	2/17 (11.8%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Pyrexia	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Chest discomfort	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Injection site pruritus	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Injection site swelling	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Pain	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Influenza like illness	0/17 (0%)		0/17 (0%)		3/13 (23.1%)		2/14 (14.3%)
Chest pain	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Non-cardiac chest pain	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Immune system disorders
Drug hypersensitivity	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Food allergy	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Hypersensitivity	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Infections and infestations
Nasopharyngitis	2/17 (11.8%)		1/17 (5.9%)		0/13 (0%)		2/14 (14.3%)
Influenza	0/17 (0%)		2/17 (11.8%)		0/13 (0%)		0/14 (0%)
Urinary tract infection	1/17 (5.9%)		1/17 (5.9%)		0/13 (0%)		1/14 (7.1%)
Sinusitis	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		1/14 (7.1%)
Cystitis	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Gastroenteritis viral	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Rash pustular	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		1/14 (7.1%)
Upper respiratory tract infection	1/17 (5.9%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Ear infection	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Syphilis	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Viral pharyngitis	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Injury, poisoning and procedural complications
Arthropod bite	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Arthropod sting	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Muscle strain	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Bone fissure	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Concussion	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Road traffic accident	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Investigations
Alanine aminotransferase increased	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Liver function test abnormal	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Weight increased	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Blood glucose increased	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	1/17 (5.9%)		2/17 (11.8%)		0/13 (0%)		1/14 (7.1%)
Back pain	2/17 (11.8%)		1/17 (5.9%)		1/13 (7.7%)		0/14 (0%)
Arthralgia	1/17 (5.9%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Bursitis	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		1/14 (7.1%)
Muscle spasms	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Myalgia	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		1/14 (7.1%)
Neck pain	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Musculoskeletal pain	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Musculoskeletal stiffness	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Skin papilloma	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Nervous system disorders
Headache	3/17 (17.6%)		4/17 (23.5%)		0/13 (0%)		2/14 (14.3%)
Dizziness	4/17 (23.5%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Paraesthesia	1/17 (5.9%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Balance disorder	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Carpal tunnel syndrome	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Hypoaesthesia	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		1/14 (7.1%)
Muscle contractions involuntary	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Migraine	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Optic neuritis	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Syncope	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Psychiatric disorders
Depression	4/17 (23.5%)		2/17 (11.8%)		0/13 (0%)		1/14 (7.1%)
Anxiety	1/17 (5.9%)		1/17 (5.9%)		0/13 (0%)		2/14 (14.3%)
Insomnia	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Renal and urinary disorders
Pollakiuria	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Stress urinary incontinence	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Urinary incontinence	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)
Reproductive system and breast disorders
Dysmenorrhoea	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Galactorrhoea	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Ovarian cyst	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	1/17 (5.9%)		2/17 (11.8%)		0/13 (0%)		1/14 (7.1%)
Tracheal pain	1/17 (5.9%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Cough	0/17 (0%)		1/17 (5.9%)		2/13 (15.4%)		0/14 (0%)
Dysphonia	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Dyspnoea	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Nasal congestion	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Pulmonary congestion	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Skin and subcutaneous tissue disorders
Rash	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Eczema	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Urticaria	0/17 (0%)		1/17 (5.9%)		0/13 (0%)		0/14 (0%)
Rosacea	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Pruritus allergic	0/17 (0%)		0/17 (0%)		1/13 (7.7%)		0/14 (0%)
Vascular disorders
Hypotension	1/17 (5.9%)		0/17 (0%)		0/13 (0%)		0/14 (0%)
Hypertension	0/17 (0%)		0/17 (0%)		0/13 (0%)		2/14 (14.3%)
Hypertensive crisis	0/17 (0%)		0/17 (0%)		0/13 (0%)		1/14 (7.1%)

Limitations/Caveats

The Sponsor voluntarily terminated this trial after observing increased Multiple Sclerosis (MS) disease activity in trial 28063 (ATAMS).

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Prior to publishing results, Institution and Principal Investigator (PI) must first provide Sponsor with a copy of proposed publication for review at least 30 days prior to submission. If Institution and PI do not agree to modification, they shall so notify Sponsor and postpone submission for additional 60 days to allow Sponsor to seek legal remedies or file patent applications. There is a need for coordinated approach to any publication of results from sites for any multi-site study.