Rheumatoid ArthritisPhase 2NCT02015520
Phase IIB Dose Ranging Study in Subjects With Moderate to Severe Rheumatoid Arthritis
A Phase 2 study testing Clazakizumab in people with Rheumatoid Arthritis, run by CSL Behring at 55 sites in 9 countries.
Trial summary
The primary purpose of this study is to identify an appropriate dose of study medication. 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?
- Clazakizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 143 participants
- Where
- 55 sitesin 9 countries
- Study dates
- Jun 2012to Jun 2015
- 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
- Diagnosis of active Rheumatoid Arthritis (RA) by standard criteria (American Rheumatism association (ARA) [1987] or American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) [2010]) at least 16 weeks prior to screening
- ACR global functional status class of 1 to 3
- Documented evidence of inadequate response tumor necrosis factor (TNF) inhibitors
- All subjects must have been receiving treatment with a minimum dose of 15 mg per week of Methotrexate for at least 12 weeks and at a stable dose for 28 days prior to screening. A dose as low as 10 mg Methotrexate is permitted if 15 mg could not be reached, due to toxicity. In Japan, Korea and Taiwan, a minimum dose of 7.5 mg per week is permitted. Additional treatment with Hydroxychloroquine or Chloroquine is permitted, if it is at a dose approved for the treatment of RA and the dose has been stable for at least 28 days prior to screening
- Minimum of 6 swollen and 6 tender joints on a 66/68 joint count at screening and at baseline (Day 1)
- Elevated High-sensitivity (hs) CRP and/or ESR
Who cannot join
- Active serious infection
- History of or active tuberculosis (TB)
- Elevated liver function tests (LFTs)
Trial locations and contacts
55 sites in 9 countries.
55 sites in 9 countries
United States21 sites
Albuquerque Center For Rheumatology
Albuquerque, New Mexico, 87102
Albuquerque Clinical Trials
Albuquerque, New Mexico, 87102
Low Country Rheumatology
Charleston, South Carolina, 29406
Joint And Muscle Medical Care And Research Institute (Jmmcri)
Charlotte, North Carolina, 28204
Cincinnati Rheumatic Disease Study Group
Cincinnati, Ohio, 45219
St. Paul Rheumatology, P.A.
Eagan, Minnesota, 55121
Physicians East, Pa
Greenville, North Carolina, 27834
Mercy Clinic Hot Springs Communities
Hot Springs, Arkansas, 71913
Rheumatology Associates Of North Alabama, P.C.
Huntsville, Alabama, 35801
Rheumatology Consultants Pllc
Knoxville, Tennessee, 37909
Physician Research Collaboration, Llc
Lincoln, Nebraska, 68516
Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.
Long Beach, California, 90806
Paramount Medical Research & Consulting, Llc
Middleburg Heights, Ohio, 44130
Center For Inflammatory Disease
Nashville, Tennessee, 37203
Arthritis & Rheumatology Center Of Oklahoma Pllc
Oklahoma City, Oklahoma, 73103
Health Research Of Oklahoma
Oklahoma City, Oklahoma, 73103
Desert Medical Advances
Palm Desert, California, 92260
Sarasota Arthritis Research Center
Sarasota, Florida, 34239
Seattle Rheumatology Associates
Seattle, Washington, 98122
Healthcare Research Consultants
Tulsa, Oklahoma, 74135
Clinical Pharmacology Study Group
Worcester, Massachusetts, 01605
Japan8 sites
Local Institution
Chiba, Chiba, 2608712
Local Institution
Kato-shi, Hyōgo, 6731462
Local Institution
Kitakyushu-shi, Fukuoka, 8078555
Local Institution
Nagano, Nagano, 3808582
Local Institution
Nishimura, Wakayama, 6492211
Local Institution
Sasebo-shi, Nagasaki, 8571195
Local Institution
Shinjuku-Ku, Tokyo, 1608582
Local Institution
Toshima-ku, Tokyo, 1708476
Mexico6 sites
Local Institution
Guadalajara
Local Institution
León, Guanajuato, 37000
Local Institution
Mérida, Yucatán, 97000
Local Institution
Mérida, Yucatán, 97070
Local Institution
San Luis Potosí City, 78200
Local Institution
Tijuana, Estado de Baja California, 22010
Argentina5 sites
Local Institution
Buenos Aires, 1121
Local Institution
Buenos Aires, 1426
Local Institution
Córdoba, 5000
Local Institution
Quilmes, Buenos Aires, 1878
Local Institution
San Miguel de Tucumán, 4000
Italy4 sites
Local Institution
Catanzaro, 88100
Local Institution
Florence, 50139
Local Institution
Naples, 80131
Local Institution
Pisa, 56126
Canada3 sites
Cividino Medicine Professional Corporation
Hamilton, Ontario, L8N 2B6
Credit Valley Rheumatology
Mississauga, Ontario, L5M 2V8
Dr. Latha Naik Medical Professional Corporation
Saskatoon, Saskatchewan, S7K 3H3
France3 sites
Local Institution
Bordeaux, 33076
Local Institution
Paris, 75679
Local Institution
Poitiers, 86021
Hungary3 sites
Local Institution
Budapest, 1023
Local Institution
Debrecen, 4012
Local Institution
Veszprém, 8200
South Africa2 sites
Local Institution
Cape Town, Western Cape, 7500
Local Institution
Stellenbosch, Western Cape, 7600
About this study
Official title: A Phase IIb, Randomized, Multi-Center, Double-Blind, Dose-Ranging Study to Evaluate the Efficacy and Safety of Clazakizumab in Subjects With Moderate to Severe Active Rheumatoid Arthritis Who Have Experienced an Inadequate Response to TNF Inhibitors
The primary purpose of this study is to identify an appropriate dose of study medication.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Clazakizumab, Placebo (Matching with Clazakizumab)
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClazakizumabDrug
Also called BMS-945429
Placebo (Matching with Clazakizumab)Drug
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Clazakizumab (Dose # A) (Double-Blind) | Experimental | Clazakizumab Dose # A injection by subcutaneous for 12 weeks + background Methotrexate Receives: Drug: Clazakizumab |
| Arm 2: Clazakizumab (Dose # B) (Double-Blind) | Experimental | Clazakizumab Dose # B injection by subcutaneous for 12 weeks + background Methotrexate Receives: Drug: Clazakizumab |
| Arm 3: Clazakizumab (Dose # C) (Double-Blind) | Experimental | Clazakizumab Dose # C injection by subcutaneous for 12 weeks + background Methotrexate Receives: Drug: Clazakizumab |
| Arm 4: Placebo matching with Clazakizumab (Double-Blind) | Experimental | Clazakizumab Dose # D injection by subcutaneous for 12 weeks + background Methotrexate Receives: Drug: Placebo (Matching with Clazakizumab) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Disease Activity Score in 28 Joints - C-reactive Protein (DAS28-CRP) at Week 12
DAS28-CRP describes severity of rheumatoid arthritis. The components of the joint count assessment are shoulder, elbow, wrist, metacarpophalangeal joints 1 through 5, proximal interphalangeal joints 1 through 5, and the knee joints on the right and left sides, whereby the number of affected joints, tender and swollen, respectively, are counted. The formula used to calculate the score is: DAS28-CRP=0.56 \times \sqrt{TEN28} + 0.28 \times \sqrt{SW28} + 0.36 \times \ln(CRP+1) + 0.014 \times SA+0.96 with:
TEN28: number of joints with tenderness upon touching SW28: number of swollen joints CRP: C-reactive Protein SA: subjective assessment of disease activity by the patient during the preceding 7 days on a scale between 0 and 100 ("0":no activity, "100": highest activity possible).
DAS-CRP score range is 0.49 to 9.07 A DAS-CRP value >5.1 corresponds to a high disease activity A DAS-28 reduction by 0.6 represents a moderate improvement. A reduction >1.2 represents a major improvement
Measured: Baseline and Week 12
Secondary outcomes (7)
American College of Rheumatology (ACR) 20/50/70 Response Rates
The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).
Measured: At week 12
Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12
CDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (SCJ) (0-28) and tender joint count (TJC) (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity. The CDAI has a range from 0 to 76.
CDAI <= 2.8 = Remission CDAI > 2.8 and <= 10 = Low Disease Activity CDAI > 10 and <= 22 = Moderate Disease Activity CDAI > 22 = High Disease Activity
Measured: Baseline and week 12
Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12
SDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (0-28) and tender joint count (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity and C-reactive protein (0-10). The SDAI has a range from 0 to 86.
0.0 - 3.3 = Remission 3.4 - 11.0 = Low Activity 11.1 - 26.0 = Moderate Activity 26.1 - 86.0 = High Activity
Measured: Baseline and week 12
Boolean Remission at Week 12
Boolean-based definition:
At any time point, a patient must satisfy all of the following:
TJC ≤1 (0-28) SJC ≤1 (0-28) CRP ≤1 mg/dl Patient Global Assessment ≤1 (on a 0-10 scale)
Measured: At week 12
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 12
Patients report the amount of difficulty they have in performing 8 categories. Each category is scored on a scale ranging from 0 (performed without any difficulty) to 3 (cannot be done at all). The HAQ-DI is then calculated by summing the scores and dividing by the number of categories answered. Total score is between 0-3.0. Increasing scores indicate worse functioning with 0 indicating no functional impairment and 3 indicating complete impairment. The HAQ-DI cannot be calculated if the subject does not have scores for at least 6 categories. A response was defined as a subject with a reduction from baseline in HAQ-DI of at least 0.22.
Measured: Baseline and Week 12
Percent of Participants With a DAS28-Erythrocyte Sedimentation Rate (ESR) <2.6
DAS28- ESR = Disease Activity Scores 28 based on erythrocyte sedimentation rate. A DAS28-ESR below 2.6 is interpreted as remission.
Measured: At week 12
Percent of Participants With a DAS28-C Reactive Protein (CRP) <2.6
DAS28-CRP = Disease Activity Scores 28 based on C Reactive Protein. A DAS28-CRP below 2.6 is interpreted as remission.
Measured: At week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2013 (estimated)
- Study startJun 2012
- Primary completionJun 2013
- Study completionJun 2015
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.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by CSL BehringThe sponsor's other registered studies.
- 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
- 143 participants (actual)
Sponsor and investigators
- Lead sponsor
- CSL Behring
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02015520
- Sponsor's protocol ID
- IM133-066
- Other IDs
- 2013-003780-65
- Status last verified
- Apr 2021
- First submitted
- 6 Dec 2013
- Last updated
- 12 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIb, Randomized, Multi-Center, Double-Blind, Dose-Ranging Study to Evaluate the Efficacy and Safety of Clazakizumab in Subjects With Moderate to Severe Active Rheumatoid Arthritis Who Have Experienced an Inadequate Response to TNF Inhibitors
- ClinicalTrials.gov ID
- NCT02015520
- Acronym / sponsor ID
- IM133-066
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 143 participants (actual)
- Lead sponsor
- CSL BehringIndustry (pharma, biotech, devices)
- Study start
- Jun 2012 (actual)
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 19 Dec 2013 (estimated)
- Results
- Posted 19 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to identify an appropriate dose of study medication.
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 |
|---|---|---|
| Arm 1: Clazakizumab (Dose # A) (Double-Blind) | Experimental | Drug: ClazakizumabClazakizumab Dose # A injection by subcutaneous for 12 weeks + background Methotrexate |
| Arm 2: Clazakizumab (Dose # B) (Double-Blind) | Experimental | Drug: ClazakizumabClazakizumab Dose # B injection by subcutaneous for 12 weeks + background Methotrexate |
| Arm 3: Clazakizumab (Dose # C) (Double-Blind) | Experimental | Drug: ClazakizumabClazakizumab Dose # C injection by subcutaneous for 12 weeks + background Methotrexate |
| Arm 4: Placebo matching with Clazakizumab (Double-Blind) | Experimental | Drug: Placebo (Matching with Clazakizumab)Clazakizumab Dose # D injection by subcutaneous for 12 weeks + background Methotrexate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of active Rheumatoid Arthritis (RA) by standard criteria (American Rheumatism association (ARA) [1987] or American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) [2010]) at least 16 weeks prior to screening
- ACR global functional status class of 1 to 3
- Documented evidence of inadequate response tumor necrosis factor (TNF) inhibitors
- All subjects must have been receiving treatment with a minimum dose of 15 mg per week of Methotrexate for at least 12 weeks and at a stable dose for 28 days prior to screening. A dose as low as 10 mg Methotrexate is permitted if 15 mg could not be reached, due to toxicity. In Japan, Korea and Taiwan, a minimum dose of 7.5 mg per week is permitted. Additional treatment with Hydroxychloroquine or Chloroquine is permitted, if it is at a dose approved for the treatment of RA and the dose has been stable for at least 28 days prior to screening
- Minimum of 6 swollen and 6 tender joints on a 66/68 joint count at screening and at baseline (Day 1)
Key exclusion criteria (3 listed)
- Active serious infection
- History of or active tuberculosis (TB)
- Elevated liver function tests (LFTs)
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 |
|---|---|---|
| ClazakizumabAlso: BMS-945429 | Drug | Arm 1: Clazakizumab (Dose # A) (Double-Blind), Arm 2: Clazakizumab (Dose # B) (Double-Blind), Arm 3: Clazakizumab (Dose # C) (Double-Blind) |
| Placebo (Matching with Clazakizumab) | Drug | Arm 4: Placebo matching with Clazakizumab (Double-Blind) |
Primary outcome
Change From Baseline in Disease Activity Score in 28 Joints - C-reactive Protein (DAS28-CRP) at Week 12
Time frame: Baseline and Week 12
DAS28-CRP describes severity of rheumatoid arthritis. The components of the joint count assessment are shoulder, elbow, wrist, metacarpophalangeal joints 1 through 5, proximal interphalangeal joints 1 through 5, and the knee joints on the right and left sides, whereby the number of affected joints, tender and swollen, respectively, are counted. The formula used to calculate the score is: DAS28-CRP=0.56 \times \sqrt{TEN28} + 0.28 \times \sqrt{SW28} + 0.36 \times \ln(CRP+1) + 0.014 \times SA+0.96 with: TEN28: number of joints with tenderness upon touching SW28: number of swollen joints CRP: C-reactive Protein SA: subjective assessment of disease activity by the patient during the preceding 7 days on a scale between 0 and 100 ("0":no activity, "100": highest activity possible). DAS-CRP score range is 0.49 to 9.07 A DAS-CRP value >5.1 corresponds to a high disease activity A DAS-28 reduction by 0.6 represents a moderate improvement. A reduction >1.2 represents a major improvement
7 secondary outcomes
American College of Rheumatology (ACR) 20/50/70 Response Rates
Time frame: At week 12
Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12
Time frame: Baseline and week 12
Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12
Time frame: Baseline and week 12
Boolean Remission at Week 12
Time frame: At week 12
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 12
Time frame: Baseline and Week 12
Percent of Participants With a DAS28-Erythrocyte Sedimentation Rate (ESR) <2.6
Time frame: At week 12
Percent of Participants With a DAS28-C Reactive Protein (CRP) <2.6
Time frame: At week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
55 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Clazakizumab in people with Rheumatoid Arthritis, run by CSL Behring at 55 sites in 9 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 6 inclusion and 3 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 12 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 55 sites in United States, Japan, Mexico, Argentina, Italy and 4 more countries. 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. 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 19 Apr 2021). 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?
Change From Baseline in Disease Activity Score in 28 Joints - C-reactive Protein (DAS28-CRP) at Week 12 (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 May 2021; AzTrials last refreshed its copy on 26 Oct 2026.