A Phase 2 Dose-finding Study of Atacicept in Subjects With Rheumatoid Arthritis (AUGUST I)

• Sponsor: EMD Serono (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00430495
• Collaborator: Merck KGaA, Darmstadt, Germany (Industry)
• Enrollment: 256
• Locations: 2
• Arms: 4
• Duration (Months): 33
• Patients Per Site: 128
• Patients Per Site Per Month: 3.9

Study Details

Study Description

Brief Summary

This was a double-blind, placebo-controlled, parallel-arm, multicentre, prospective dose-finding trial of the safety and efficacy of atacicept in subjects with active rheumatoid arthritis who had failed a three month therapeutic trial with a tumor necrosis factor alpha (TNFa) antagonist due to lack of efficacy.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 256 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Multicentre, Phase II Dose-finding Study of Atacicept Given Subcutaneously in Subjects With Rheumatoid Arthritis and Inadequate Response to TNFa Antagonist Therapy
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Atacicept 25 mg	Drug: Atacicept; Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks.
Experimental: Atacicept 75 mg	Drug: Atacicept; Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 weeks.
Experimental: Atacicept 150 mg	Drug: Atacicept; 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 21 weeks.
Placebo Comparator: Placebo	Drug: Placebo matched to atacicept; Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP) at Week 26 [Week 26]

   ACR20-CRP response is defined as greater than or equal to (>=) 20 percent (%) improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=20% improvement in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP).

Secondary Outcome Measures

1. Percentage of Participants Achieving American College of Rheumatology 50 Response Based on CRP (ACR50-CRP) at Week 26 [Week 26]

   ACR50-CRP response is defined as >=50% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=50% improvement in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP).

2. Percentage of Participants Achieving American College of Rheumatology 70 Response Based on CRP (ACR70-CRP) at Week 26 [Week 26]

   ACR70-CRP response is defined as >=70% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=70% improvement in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP).

3. Percentage of Participants Achieving Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) of Less Than or Equal to (<=) 3.2 at Week 26 [Week 26]

   DAS28-CRP incorporates non-graded joint counts for tenderness and swelling based on a total of 28 joints, CRP as a marker of inflammation, and a general health assessment using a 100-millimeter (mm) visual analog scale (the participant's global assessment of disease activity). DAS28 ranges between 0 and 10 representing current disease activity. A value above 5.1 represents high disease activity, a value below 3.2 represents low disease activity, and a value below 2.6 represents remission.

4. Percentage of Participants Achieving Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) of <=2.6 at Week 26 [Week 26]

   DAS28-CRP incorporates non-graded joint counts for tenderness and swelling based on a total of 28 joints, CRP as a marker of inflammation, and a general health assessment using a 100 mm visual analog scale (the participant's global assessment of disease activity). DAS28 ranges between 0 and 10 representing current disease activity. A value above 5.1 represents high disease activity, a value below 3.2 represents low disease activity, and a value below 2.6 represents remission.

5. Percentage of Participants Achieving Improvement in Health Assessment Questionnaire Disability Index (HAQ-DI) of at Least 0.3 From Baseline at Week 26 [Week 26]

   The HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item was scored on 4-point scale from 0 to 3: 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range is 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. Percentage of participants achieving improvement in HAQ-DI of at least 0.3 from baseline at Week 26 was reported.

6. Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 26 [Week 26]

   The EULAR response criteria evaluate change in DAS28 scores represented as "good response", "moderate response", or "no response" considering both the current DAS28 score and the observed improvement from baseline. Participants were considered to have "good" or "moderate" EULAR response if at the time of assessment, their DAS28 score was <=5.1 and the improvement from baseline in their DAS28 score was greater than (>) 0.6; or if at the time of assessment, their DAS28 score was >5.1 and improvement from baseline in their DAS28 score was >1.2.

7. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline up to Week 38]

   An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Rheumatoid arthritis (RA) satisfying American College of Rheumatology (ACR) diagnostic criteria with a disease history of at least one year

2. Male or female greater than or equal to (>=)18-years of age at time of informed consent

3. Active RA as defined by:

• =8 swollen joints (66-joint count),

• =8 tender joints (68-joint count), and

• C-reactive protein (CRP) >=10 milligram per liter (mg/L) (central laboratory) and/or erythrocyte sedimentation rate (ESR) >= to 28 millimeter per hour (mm/h)

1. Failure of at least one TNFa antagonist therapy (previously or at the time of screening) as specified in the protocol

2. Other protocol defined inclusion criteria could apply

Exclusion Criteria:

1. Any condition, including laboratory findings or findings in the medical history or pre-trial assessments, that in the opinion of the Investigator constitutes a risk or a contraindication for the subject's participation in the trial or that could interfere with the trial objectives, conduct or evaluation

2. Treatment with biologics aiming at B cell modulation such as rituximab or belimumab within 2 years before study Day 1

3. Any previous treatment with anakinra (Kineret), abatacept (Orencia) or tocilizumab within 3 months before study Day 1

4. Use of etanercept (Enbrel) within 28 days before study Day 1, or of infliximab (Remicade) or adalimumab (Humira) within 60 days before study Day 1

5. Participation in any interventional clinical trial with an unapproved investigational therapy within the 3 months before the start of this study (or within 5 half-lives of the investigated compound before study Day 1, whichever is longer)

6. Other protocol defined exclusion criteria could apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	EMD Serono	Rockland	Massachusetts	United States	02370
2	Merck/Serono	Canada		Canada

Sponsors and Collaborators

• EMD Serono
• Merck KGaA, Darmstadt, Germany

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: EMD Serono
• ClinicalTrials.gov Identifier: NCT00430495
• Other Study ID Numbers: 27298
• First Posted: Feb 2, 2007
• Last Update Posted: Feb 17, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by EMD Serono: atacicept; arthritis
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

Participant Flow

Pre-assignment Detail	A total of 456 subjects were screened, of whom 256 were enrolled and randomized of which 254 received the trial medication and included in Intention to Treat (ITT) population.

Arm/Group Title	Placebo	Atacicept 25 mg	Atacicept 75 mg	Atacicept 150 mg
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 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 21 weeks.
Period Title: Overall Study
STARTED	64	66	62	64
Treated	62	66	62	64
COMPLETED	50	59	49	60
NOT COMPLETED	14	7	13	4

Baseline Characteristics

Arm/Group Title	Placebo	Atacicept 25 mg	Atacicept 75 mg	Atacicept 150 mg	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 21 weeks.	Atacicept was administered subcutaneously at a dose of 25 mg twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 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 21 weeks.	Total of all reporting groups
Overall Participants	62	66	62	64	254
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.1 (12.5)	53.4 (13.1)	55.3 (12.0)	53.5 (10.1)	53.8 (11.9)
Sex: Female, Male (Count of Participants)
Female	51 82.3%	54 81.8%	53 85.5%	53 82.8%	211 83.1%
Male	11 17.7%	12 18.2%	9 14.5%	11 17.2%	43 16.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP) at Week 26
Description	ACR20-CRP response is defined as greater than or equal to (>=) 20 percent (%) improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=20% improvement in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 treatment dose.

Arm/Group Title	Placebo	Atacicept 25 mg	Atacicept 75 mg	Atacicept 150 mg
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 25 mg twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 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 21 weeks.
Measure Participants	62	66	62	64
Number [percentage of participants]	29.0 46.8%	30.3 45.9%	27.4 44.2%	39.1 61.1%

2. Secondary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 50 Response Based on CRP (ACR50-CRP) at Week 26
Description	ACR50-CRP response is defined as >=50% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=50% improvement in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 treatment dose.

Arm/Group Title	Placebo	Atacicept 25 mg	Atacicept 75 mg	Atacicept 150 mg
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 25 mg twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 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 21 weeks.
Measure Participants	62	66	62	64
Number [percentage of participants]	6.5 10.5%	13.6 20.6%	11.3 18.2%	10.9 17%

3. Secondary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 70 Response Based on CRP (ACR70-CRP) at Week 26
Description	ACR70-CRP response is defined as >=70% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=70% improvement in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 treatment dose.

Arm/Group Title	Placebo	Atacicept 25 mg	Atacicept 75 mg	Atacicept 150 mg
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 25 mg twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 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 21 weeks.
Measure Participants	62	66	62	64
Number [percentage of participants]	0.0 0%	6.1 9.2%	4.8 7.7%	0.0 0%

4. Secondary Outcome

Title	Percentage of Participants Achieving Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) of Less Than or Equal to (<=) 3.2 at Week 26
Description	DAS28-CRP incorporates non-graded joint counts for tenderness and swelling based on a total of 28 joints, CRP as a marker of inflammation, and a general health assessment using a 100-millimeter (mm) visual analog scale (the participant's global assessment of disease activity). DAS28 ranges between 0 and 10 representing current disease activity. A value above 5.1 represents high disease activity, a value below 3.2 represents low disease activity, and a value below 2.6 represents remission.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 treatment dose.

Arm/Group Title	Placebo	Atacicept 25 mg	Atacicept 75 mg	Atacicept 150 mg
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 25 mg twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 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 21 weeks.
Measure Participants	62	66	62	64
Number [percentage of participants]	9.7 (0.95) 15.6%	10.6 (0.84) 16.1%	9.7 (0.88) 15.6%	12.5 (0.84) 19.5%

5. Secondary Outcome

Title	Percentage of Participants Achieving Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) of <=2.6 at Week 26
Description	DAS28-CRP incorporates non-graded joint counts for tenderness and swelling based on a total of 28 joints, CRP as a marker of inflammation, and a general health assessment using a 100 mm visual analog scale (the participant's global assessment of disease activity). DAS28 ranges between 0 and 10 representing current disease activity. A value above 5.1 represents high disease activity, a value below 3.2 represents low disease activity, and a value below 2.6 represents remission.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 treatment dose.

Arm/Group Title	Placebo	Atacicept 25 mg	Atacicept 75 mg	Atacicept 150 mg
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 25 mg twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 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 21 weeks.
Measure Participants	62	66	62	64
Number [percentage of participants]	1.6 2.6%	6.1 9.2%	4.8 7.7%	4.7 7.3%

6. Secondary Outcome

Title	Percentage of Participants Achieving Improvement in Health Assessment Questionnaire Disability Index (HAQ-DI) of at Least 0.3 From Baseline at Week 26
Description	The HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item was scored on 4-point scale from 0 to 3: 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range is 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. Percentage of participants achieving improvement in HAQ-DI of at least 0.3 from baseline at Week 26 was reported.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 treatment dose. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	Atacicept 25 mg	Atacicept 75 mg	Atacicept 150 mg
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 25 mg twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 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 21 weeks.
Measure Participants	38	41	34	48
Number [percentage of participants]	47.4 76.5%	48.8 73.9%	55.9 90.2%	37.5 58.6%

7. Secondary Outcome

Title	Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 26
Description	The EULAR response criteria evaluate change in DAS28 scores represented as "good response", "moderate response", or "no response" considering both the current DAS28 score and the observed improvement from baseline. Participants were considered to have "good" or "moderate" EULAR response if at the time of assessment, their DAS28 score was <=5.1 and the improvement from baseline in their DAS28 score was greater than (>) 0.6; or if at the time of assessment, their DAS28 score was >5.1 and improvement from baseline in their DAS28 score was >1.2.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 treatment dose.

Arm/Group Title	Placebo	Atacicept 25 mg	Atacicept 75 mg	Atacicept 150 mg
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 25 mg twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 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 21 weeks.
Measure Participants	62	66	62	64
Number [percentage of participants]	41.9 67.6%	31.8 48.2%	35.5 57.3%	53.1 83%

8. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Time Frame	Baseline up to Week 38

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who received at least 1 treatment dose and had safety data following their first dose.

Arm/Group Title	Placebo	Atacicept 25 mg	Atacicept 75 mg	Atacicept 150 mg
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 25 mg twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks.	Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 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 21 weeks.
Measure Participants	62	66	62	64
AEs	41 66.1%	49 74.2%	42 67.7%	46 71.9%
SAEs	3 4.8%	9 13.6%	8 12.9%	5 7.8%

Adverse Events

Time Frame	Baseline up to Week 38
Arm/Group Title	Placebo		Atacicept 25 mg		Atacicept 75 mg		Atacicept 150 mg
Arm/Group Description	Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.		Atacicept was administered subcutaneously at a dose of 25 mg twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks.		Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 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 21 weeks.
All Cause Mortality
	Placebo		Atacicept 25 mg		Atacicept 75 mg		Atacicept 150 mg
	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		Atacicept 25 mg		Atacicept 75 mg		Atacicept 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/62 (4.8%)		9/66 (13.6%)		8/62 (12.9%)		5/64 (7.8%)
Blood and lymphatic system disorders
Anaemia	0/62 (0%)		1/66 (1.5%)		0/62 (0%)		0/64 (0%)
Cardiac disorders
Acute myocardial infarction	0/62 (0%)		0/66 (0%)		1/62 (1.6%)		0/64 (0%)
Angina pectoris	0/62 (0%)		0/66 (0%)		1/62 (1.6%)		0/64 (0%)
Cardio-respiratory arrest	0/62 (0%)		0/66 (0%)		1/62 (1.6%)		0/64 (0%)
Right ventricular failure	0/62 (0%)		0/66 (0%)		0/62 (0%)		1/64 (1.6%)
Endocrine disorders
Basedow's disease	1/62 (1.6%)		0/66 (0%)		0/62 (0%)		0/64 (0%)
Hyperthyroidism	0/62 (0%)		1/66 (1.5%)		0/62 (0%)		0/64 (0%)
Gastrointestinal disorders
Diverticular perforation	0/62 (0%)		1/66 (1.5%)		0/62 (0%)		0/64 (0%)
Inguinal hernia	0/62 (0%)		0/66 (0%)		0/62 (0%)		1/64 (1.6%)
Intestinal obstruction	0/62 (0%)		1/66 (1.5%)		0/62 (0%)		0/64 (0%)
General disorders
Non-cardiac chest pain	0/62 (0%)		1/66 (1.5%)		0/62 (0%)		0/64 (0%)
Pyrexia	0/62 (0%)		1/66 (1.5%)		0/62 (0%)		0/64 (0%)
Immune system disorders
Drug hypersensitivity	0/62 (0%)		1/66 (1.5%)		0/62 (0%)		0/64 (0%)
Infections and infestations
Bronchitis	0/62 (0%)		0/66 (0%)		0/62 (0%)		1/64 (1.6%)
Pyopneumothorax	0/62 (0%)		0/66 (0%)		0/62 (0%)		1/64 (1.6%)
Relapsing fever	0/62 (0%)		1/66 (1.5%)		0/62 (0%)		0/64 (0%)
Stenotrophomonas infection	0/62 (0%)		0/66 (0%)		0/62 (0%)		1/64 (1.6%)
Injury, poisoning and procedural complications
Femur fracture	1/62 (1.6%)		1/66 (1.5%)		0/62 (0%)		0/64 (0%)
Hip fracture	0/62 (0%)		0/66 (0%)		2/62 (3.2%)		0/64 (0%)
Humerus fracture	0/62 (0%)		1/66 (1.5%)		0/62 (0%)		0/64 (0%)
Pelvic fracture	0/62 (0%)		1/66 (1.5%)		0/62 (0%)		0/64 (0%)
Upper limb fracture	0/62 (0%)		1/66 (1.5%)		0/62 (0%)		0/64 (0%)
Investigations
Fibrin D dimer increased	0/62 (0%)		1/66 (1.5%)		0/62 (0%)		0/64 (0%)
Gamma-glutamyltransferase increased	0/62 (0%)		1/66 (1.5%)		0/62 (0%)		0/64 (0%)
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	0/62 (0%)		2/66 (3%)		2/62 (3.2%)		0/64 (0%)
Back pain	1/62 (1.6%)		0/66 (0%)		0/62 (0%)		0/64 (0%)
Osteonecrosis	0/62 (0%)		0/66 (0%)		1/62 (1.6%)		0/64 (0%)
Nervous system disorders
Migraine	1/62 (1.6%)		0/66 (0%)		0/62 (0%)		0/64 (0%)
Vasculitis cerebral	0/62 (0%)		0/66 (0%)		1/62 (1.6%)		0/64 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/62 (0%)		0/66 (0%)		0/62 (0%)		1/64 (1.6%)
Reproductive system and breast disorders
Fallopian tube cyst	0/62 (0%)		1/66 (1.5%)		0/62 (0%)		0/64 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/62 (1.6%)		0/66 (0%)		0/62 (0%)		0/64 (0%)
Skin and subcutaneous tissue disorders
Angioedema	0/62 (0%)		0/66 (0%)		1/62 (1.6%)		0/64 (0%)
Surgical and medical procedures
Prostatic operation	0/62 (0%)		0/66 (0%)		0/62 (0%)		1/64 (1.6%)
Other (Not Including Serious) Adverse Events
	Placebo		Atacicept 25 mg		Atacicept 75 mg		Atacicept 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/62 (24.2%)		25/66 (37.9%)		16/62 (25.8%)		26/64 (40.6%)
Blood and lymphatic system disorders
Iron deficiency anaemia	0/62 (0%)		1/66 (1.5%)		0/62 (0%)		4/64 (6.3%)
Gastrointestinal disorders
Diarrhoea	1/62 (1.6%)		4/66 (6.1%)		6/62 (9.7%)		5/64 (7.8%)
Nausea	1/62 (1.6%)		5/66 (7.6%)		4/62 (6.5%)		1/64 (1.6%)
Constipation	1/62 (1.6%)		4/66 (6.1%)		1/62 (1.6%)		2/64 (3.1%)
Infections and infestations
Upper respiratory tract infection	4/62 (6.5%)		3/66 (4.5%)		0/62 (0%)		8/64 (12.5%)
Urinary tract infection	3/62 (4.8%)		4/66 (6.1%)		3/62 (4.8%)		5/64 (7.8%)
Nasopharyngitis	1/62 (1.6%)		3/66 (4.5%)		1/62 (1.6%)		4/64 (6.3%)
Nervous system disorders
Headache	4/62 (6.5%)		12/66 (18.2%)		5/62 (8.1%)		3/64 (4.7%)
Vascular disorders
Hypertension	5/62 (8.1%)		3/66 (4.5%)		3/62 (4.8%)		2/64 (3.1%)

Limitations/Caveats

[Not Specified]

More Information

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.