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

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Atacicept
Atacicept
Atacicept
Placebo matched to atacicept
Sponsored by
EMD Serono
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring atacicept, arthritis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)
  4. Failure of at least one TNFa antagonist therapy (previously or at the time of screening) as specified in the protocol
  5. 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

Sites / Locations

  • EMD Serono
  • Merck/Serono

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Atacicept 25 mg

Atacicept 75 mg

Atacicept 150 mg

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP) at 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

Percentage of Participants Achieving American College of Rheumatology 50 Response Based on CRP (ACR50-CRP) at 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).
Percentage of Participants Achieving American College of Rheumatology 70 Response Based on CRP (ACR70-CRP) at 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).
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
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.
Percentage of Participants Achieving Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) of <=2.6 at 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.
Percentage of Participants Achieving Improvement in Health Assessment Questionnaire Disability Index (HAQ-DI) of at Least 0.3 From Baseline at 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.
Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at 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.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.

Full Information

First Posted
January 30, 2007
Last Updated
January 19, 2016
Sponsor
EMD Serono
Collaborators
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT00430495
Brief Title
A Phase 2 Dose-finding Study of Atacicept in Subjects With Rheumatoid Arthritis (AUGUST I)
Acronym
AUGUST I
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 Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
December 2006 (undefined)
Primary Completion Date
September 2009 (Actual)
Study Completion Date
September 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
EMD Serono
Collaborators
Merck KGaA, Darmstadt, Germany

4. Oversight

Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
atacicept, arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
256 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Atacicept 25 mg
Arm Type
Experimental
Arm Title
Atacicept 75 mg
Arm Type
Experimental
Arm Title
Atacicept 150 mg
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Atacicept
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Atacicept
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Atacicept
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo matched to atacicept
Intervention Description
Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Rheumatoid arthritis (RA) satisfying American College of Rheumatology (ACR) diagnostic criteria with a disease history of at least one year Male or female greater than or equal to (>=)18-years of age at time of informed consent 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) Failure of at least one TNFa antagonist therapy (previously or at the time of screening) as specified in the protocol Other protocol defined inclusion criteria could apply Exclusion Criteria: 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 Treatment with biologics aiming at B cell modulation such as rituximab or belimumab within 2 years before study Day 1 Any previous treatment with anakinra (Kineret), abatacept (Orencia) or tocilizumab within 3 months before study Day 1 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 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) Other protocol defined exclusion criteria could apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
EMD Serono, an affiliate of Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
EMD Serono
City
Rockland
State/Province
Massachusetts
ZIP/Postal Code
02370
Country
United States
Facility Name
Merck/Serono
City
Canada
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
21452293
Citation
Genovese MC, Kinnman N, de La Bourdonnaye G, Pena Rossi C, Tak PP. Atacicept in patients with rheumatoid arthritis and an inadequate response to tumor necrosis factor antagonist therapy: results of a phase II, randomized, placebo-controlled, dose-finding trial. Arthritis Rheum. 2011 Jul;63(7):1793-803. doi: 10.1002/art.30373.
Results Reference
derived

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

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