Rheumatoid ArthritisPhase 2AUGUST INCT00430495
A Phase 2 Dose-finding Study of Atacicept in Subjects With Rheumatoid Arthritis (AUGUST I)
A Phase 2 study testing Atacicept in people with Rheumatoid Arthritis, run by EMD Serono at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Atacicept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 256 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Dec 2006to Sep 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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
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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Atacicept, Placebo matched to atacicept
- Keywords
- atacicept, arthritis
- Medical subject headings
- Arthritis, Rheumatoid, Arthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtaciceptDrug
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.
AtaciceptDrug
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.
AtaciceptDrug
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 matched to ataciceptDrug
Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Atacicept 25 mg | Experimental | Not described Receives: Drug: Atacicept |
| Atacicept 75 mg | Experimental | Not described Receives: Drug: Atacicept |
| Atacicept 150 mg | Experimental | Not described Receives: Drug: Atacicept |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo matched to atacicept |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Week 26
Secondary outcomes (7)
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).
Measured: Week 26
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).
Measured: Week 26
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.
Measured: Week 26
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.
Measured: Week 26
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.
Measured: Week 26
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.
Measured: Week 26
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.
Measured: Baseline up to Week 38
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2007 (estimated)
- Study startDec 2006
- Primary completionSep 2009
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 256 participants (actual)
Sponsor and investigators
- Lead sponsor
- EMD Serono
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, EMD Serono, an affiliate of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00430495
- Sponsor's protocol ID
- 27298
- Acronym
- AUGUST I
- Status last verified
- Jan 2016
- First submitted
- 30 Jan 2007
- Last updated
- 17 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 21452293
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00430495
- Acronym / sponsor ID
- AUGUST I / 27298
- Conditions
- Rheumatoid Arthritis
- Keywords
- atacicept, arthritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 256 participants (actual)
- Lead sponsor
- EMD SeronoIndustry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Study start
- Dec 2006
- Primary completion
- Sep 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 2 Feb 2007 (estimated)
- Results
- Posted 17 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Atacicept 25 mg | Experimental | Drug: Atacicept |
| Atacicept 75 mg | Experimental | Drug: Atacicept |
| Atacicept 150 mg | Experimental | Drug: Atacicept |
| Placebo | Placebo comparator | Drug: Placebo matched to atacicept |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
- 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
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtaciceptAtacicept 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. | Drug | Atacicept 25 mg |
| AtaciceptAtacicept 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. | Drug | Atacicept 75 mg |
| AtaciceptAtacicept 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. | Drug | Atacicept 150 mg |
| Placebo matched to ataciceptPlacebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks. | Drug | Placebo |
Primary outcome
Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP) at Week 26
Time frame: 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).
7 secondary outcomes
Percentage of Participants Achieving American College of Rheumatology 50 Response Based on CRP (ACR50-CRP) at Week 26
Time frame: Week 26
Percentage of Participants Achieving American College of Rheumatology 70 Response Based on CRP (ACR70-CRP) at Week 26
Time frame: Week 26
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
Time frame: Week 26
Percentage of Participants Achieving Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) of <=2.6 at Week 26
Time frame: Week 26
Percentage of Participants Achieving Improvement in Health Assessment Questionnaire Disability Index (HAQ-DI) of at Least 0.3 From Baseline at Week 26
Time frame: Week 26
Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 26
Time frame: Week 26
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to Week 38
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21452293Genovese 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
EMD Serono, an affiliate of Merck KGaA, Darmstadt, Germany
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atacicept in people with Rheumatoid Arthritis, run by EMD Serono at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP) at Week 26 (time frame: Week 26). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00430495, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2016.