Rheumatoid ArthritisPhase 2NCT00487825
Safety and Efficacy of Intravenous ACZ885 and Oral Methotrexate Therapy in Patients With Early Rheumatoid Arthritis
A Phase 2 study testing Canakinumab (investigational) and Methotrexate (MTX) in people with Rheumatoid Arthritis, run by Novartis at 22 sites in 6 countries.
Trial summary
This study was intended to evaluate the safety and efficacy of intravenous (IV) ACZ885 and oral methotrexate (MTX) therapy in patients with early rheumatoid arthritis (RA) Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Canakinumab (investigational) and Methotrexate (MTX)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 22 sitesin 6 countries
- Study dates
- Mar 2007to Dec 2008
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients of 18 to 75 years of age (inclusive)
- Recent definite diagnosis of rheumatoid arthritis (RA) (<3 years since diagnosis), classified by American Rheumatism Association 1987 revised criteria.
- Candidate for methotrexate (MTX) or biologic due to erosive arthritis, with no contraindications to such therapy, including:
- Negative tuberculin skin test reaction
- Normal chest X-ray (within the last year) prior to possibility of receiving MTX (r/o lung fibrosis).
- Active disease: at least 6 swollen and 6 painful tender joints of 28 joint count,
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- Vital signs should be within the following ranges:
- 18-59 years of age: oral temperature between 35.0-37.5 °C systolic blood pressure, 90-140 mm Hg diastolic blood pressure, 50-90 mm Hg pulse rate, 40 - 90 beats per minute
- 60-75 years of age: oral temperature between 35.0-37.5 °C systolic blood pressure, 100-160 mm Hg diastolic blood pressure, 50-100 mm Hg pulse rate, 50 - 100 beats per minute
- Women of child-bearing potential willing to practice double-barrier contraception during the study for at least 3 months following last study drug administration. Postmenopausal women must have no regular menstrual bleeding for at least 1 year prior to inclusion. Surgically sterilized women at least 6 months prior to screening.
- Male patients must be using a double-barrier local contraception and refrain from fathering a child in the 3 months following last study drug administration.
- Weight: at least 45 kg; body mass index (BMI) within the range of 18 to 34.
- Oral corticosteroids are permitted as long as patients are on a stable dose (up to 10 mg) for at least 4 weeks before study start.
Who cannot join
- Unable to have Magnetic Resonance Imaging (MRI) of wrist.
- Patients with magnetizable metal parts/devices on and in the body that could interfere with the MRI
- Patients with an unstable active medical condition that could impair evaluation of study results.
- Previous treatment with biological therapy or MTX.
- Limited kidney function (creatinine clearance under 60 ml/min)
- Previous treatment with other disease-modifying anti-rheumatic drugs such as sulfasalazine, hydroxychloroquine within 4 weeks of screening.
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- Corticosteroids injections into joints within 4 weeks prior to screening.
- Participation in any clinical investigation within 4 weeks prior to study start or longer if required by local regulations, and for any other limitation of participation based on local regulations.
- Blood donation or loss of > 400 mL within 8 weeks before study start, or longer if required by local regulation.
- Significant illness within 2 weeks of study start.
- Past personal or family medical history of clinically significant ECG abnormalities or cardiac issues.
- History of:
- fainting, orthostatic hypotension, sinus arrhythmia asthma and chronic obstructive pulmonary disease, clinically significant drug allergy or urticaria, eczematous dermatitis, and/or known hypersensitivity to the study drug or drugs similar to the study drug.
- disease of the blood building system, serious or active infections, gastric ulcers.
- surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs or which may jeopardize the patient in case of participation in the study.
- immunodeficiency diseases, including a positive Human Immunodeficiency Virus (HIV) (ELISA and Western blot) test result.
- positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.
- drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse.
Trial locations and contacts
22 sites in 6 countries.
22 sites in 6 countries
United States17 sites
Arthritis Clinic of Northern Virginia (Dr. Philip Kempf)
Arlington, Virginia, 22205
MetaClin Research, Incorporated (Dr. Paul Pickrell)
Austin, Texas, 78704
John M. Joseph, MD (Dr. John Joseph)
Carlton, Texas, 75007
Rheumatology Associates of Northern Alabama (Dr. William Shergy)
Huntsville, Alabama, 35801
Jacksonville Center for Clinical Research (Dr. Steven Mathews)
Jacksonville, Florida, 32216
Southwest Rheumatology, P.A. (Dr. Atul Singhal)
Mesquite, Texas, 75150
Westroads Medical Group (Dr. William Palmer)
Omaha, Nebraska, 68114
Arizona Arthritis and Rheumatology Research (Dr. Paul Caldron)
Paradise Valley, Arizona, 85253
Arthritis Center of Reno (Dr. Malin Prupas)
Reno, Nevada, 89502
Clayton Medical Research (Dr. Iri Don)
Richmond Heights, Missouri, 63117
Rockford Orthopedic Associates (Dr. Richard Olson)
Rockford, Illinois, 61107
Center for Arthritis and Rheumatic Diseases (Dr. Michael Weitz)
South Miami, Florida, 33143
Arthritis Northwest Rheumatology, PLLC (Dr. Jeffrey Butler)
Spokane, Washington, 99204
West Broward Rheumatology Associates, Incorporated (Dr. Elias Halpert)
Tamarac, Florida, 33321
Oklahoma Center for Arthritis therapy and Research (Dr. James McKay)
Tulsa, Oklahoma, 74104
Clinic for Rheumatic Diseases (Dr. Richard Jones, III)
Tuscaloosa, Alabama, 35406
Mercy Arthritis and Osteoporosis Center (Dr. Alan Braun)
Urbandale, Iowa, 50322
About this study
Official title: A 26-week, Phase II, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Assess the Response to Treatment (ACR50) and to Determine a Biomarker Profile in Responders to ACZ885 (Anti-interleukin-1beta Monoclonal Antibody) Plus MTX as Compared to MTX Alone in Early Rheumatoid Arthritis Patients
This study was intended to evaluate the safety and efficacy of intravenous (IV) ACZ885 and oral methotrexate (MTX) therapy in patients with early rheumatoid arthritis (RA)
- Conditions
- Rheumatoid Arthritis
- Being tested
- Canakinumab (investigational), Placebo, Methotrexate (MTX)
- Keywords
- ACR20, ACR50, ACZ885 (anti-interleukin-1beta monoclonal antibody), rheumatoid arthritis, methotrexate
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Canakinumab (investigational)Drug
Also called ACZ885
Canakinumab was supplied in 6 mL colorless glass vials each containing nominally 150 mg canakinumab (with 20% overfill). The vials were kept at 2-8°C. At the investigator's site, solutions for infusion were prepared depending on the volume and dose administered.
PlaceboDrug
Matching placebo was supplied in form of a lyophilized cake (Powder for Solution for Infusion). At the investigator's site, solutions for infusion were prepared depending on the volume and dose administered.
Methotrexate (MTX)Drug
Methotrexate (MTX) was supplied in tablet form, each of 2.5 mg strength.
| Study group | Role | What they receive |
|---|---|---|
| Canakinumab + Methotrexate | Experimental | Canakinumab, human anti-interleukin-1beta monoclonal antibody plus Methotrexate (MTX). Intravenous (IV) Infusion of 600mg canakinumab on Day 1, 15 continuing every 4 weeks up to week 26. MTX was given as variable dosing regimen of 7.5 mg-15 mg weekly. Receives: Drug: Canakinumab (investigational); Drug: Methotrexate (MTX) |
| Methotrexate + placebo | Active comparator | Methotrexate (MTX) was given as variable dosing regimen of 7.5 mg-15 mg weekly. Intravenous (IV) Placebo Solution, given in the same mode of administration as the canakinumab solution. Receives: Drug: Placebo; Drug: Methotrexate (MTX) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response to Intravenous Canakinumab and Oral Methotrexate (MTX) Compared to MTX Alone as Determined by 50% Improvement in Symptoms According to the American College of Rheumatology Criteria (ACR50)
A patient was considered as improved according to the ACR50 criteria if she/he had at least a 50 % improvement in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures:
- Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm)
- Patient's global assessment of disease activity (VAS 100 mm)
- Physician's global assessment of disease activity (VAS 100 mm)
- Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score)
- Acute phase reactant (high sensitivity C-reactive Protein (hsCRP))
Measured: 6, 14, and 26 weeks of treatment
Secondary outcomes (3)
Response to Intravenous (IV) Canakinumab and Oral Methotrexate (MTX) Therapy (ACR20, 70, 90) Compared to MTX Alone
A patient was considered as improved according to the criteria of ACR 20 equaling at least 20%, ACR70 = 70%, and ACR90 = 90% improvement in the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures:
- Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm)
- Patient's global assessment of disease activity (VAS 100 mm)
- Physician's global assessment of disease activity (VAS 100 mm)
- Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score)
- Acute phase reactant (high sensitivity C-reactive Protein (hsCRP))
Measured: At 6 weeks, 14 weeks, and 26 weeks
Percentage of Participants Achieving a Good European League Against Rheumatism (EULAR) Response (Based on the Disease Activity Score (DAS28)) at 26 Weeks
At each visit (including baseline) the DAS28 is derived as: DAS28 = 0.56*√ (tender28) + 0.28 * √ (swollen28) + 0.36 * loge(CRP+1) + 0.014*PGDA+ 0.96; where tender28 is the tender 28-joint count, swollen28 is the swollen 28-joint count, PGDA is the patient's global assessment of disease activity. Patients can be scored on a range of 0 to 10. When current DAS < 3.2, good response is defined as >1.2 improvement in DAS from baseline and non-response is improvement of ≤0.6. When current DAS >5.1, non-response is improvement of >0.6 but ≤1.2 . All others are moderate responses.
Measured: At 26 weeks
The Number of Participants in Clinical Remission Based on Disease Activity Score (DAS)28 and Simplified Disease Activity Index (SDAI)
At each visit (including baseline) the DAS28 and SDAI variables were derived using the following formulas:
DAS28 = 0.56*√ (tender28) + 0.28 * √ (swollen28) + 0.36 * loge(CRP+1) + 0.014*PGDA+ 0.96; SDAI = tender28 + swollen28 + CRP + (PGDA / 10) + (EGDA / 10) where tender28 is the tender 28-joint count, swollen28 is the swollen 28-joint count, CRP is C-reactive protein, PGDA is the patient's global assessment of disease activity and EGDA is the physician's global assessment of disease activity.
The Number of Participants in clinical remission is defined as the DAS28 ≤ 2.6 or SDAI ≤ 3.3.
Measured: At 6 weeks, 14 weeks and 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2007 (estimated)
- Study startMar 2007
- Primary completionDec 2008
- Study completionDec 2008
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.
- 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
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis, Principal investigator, Investigative site
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00487825
- Sponsor's protocol ID
- CACZ885A2204
- Status last verified
- Jul 2012
- First submitted
- 18 Jun 2007
- Last updated
- 1 Aug 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 26-week, Phase II, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Assess the Response to Treatment (ACR50) and to Determine a Biomarker Profile in Responders to ACZ885 (Anti-interleukin-1beta Monoclonal Antibody) Plus MTX as Compared to MTX Alone in Early Rheumatoid Arthritis Patients
- ClinicalTrials.gov ID
- NCT00487825
- Acronym / sponsor ID
- CACZ885A2204
- Conditions
- Rheumatoid Arthritis
- Keywords
- ACR20, ACR50, ACZ885 (anti-interleukin-1beta monoclonal antibody), rheumatoid arthritis, methotrexate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- NovartisIndustry (pharma, biotech, devices)
- Study start
- Mar 2007
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 19 Jun 2007 (estimated)
- Results
- Posted 6 May 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study was intended to evaluate the safety and efficacy of intravenous (IV) ACZ885 and oral methotrexate (MTX) therapy in patients with early rheumatoid arthritis (RA)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Canakinumab + Methotrexate | Experimental | Drug: Canakinumab (investigational), Drug: Methotrexate (MTX)Canakinumab, human anti-interleukin-1beta monoclonal antibody plus Methotrexate (MTX). Intravenous (IV) Infusion of 600mg canakinumab on Day 1, 15 continuing every 4 weeks up to week 26. MTX was given as variable dosing regimen of 7.5 mg-15 mg weekly. |
| Methotrexate + placebo | Active comparator | Drug: Placebo, Drug: Methotrexate (MTX)Methotrexate (MTX) was given as variable dosing regimen of 7.5 mg-15 mg weekly. Intravenous (IV) Placebo Solution, given in the same mode of administration as the canakinumab solution. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Male and female patients of 18 to 75 years of age (inclusive)
- Recent definite diagnosis of rheumatoid arthritis (RA) (<3 years since diagnosis), classified by American Rheumatism Association 1987 revised criteria.
- Candidate for methotrexate (MTX) or biologic due to erosive arthritis, with no contraindications to such therapy, including:
- Negative tuberculin skin test reaction
- Normal chest X-ray (within the last year) prior to possibility of receiving MTX (r/o lung fibrosis).
Key exclusion criteria (18 listed)
- Unable to have Magnetic Resonance Imaging (MRI) of wrist.
- Patients with magnetizable metal parts/devices on and in the body that could interfere with the MRI
- Patients with an unstable active medical condition that could impair evaluation of study results.
- Previous treatment with biological therapy or MTX.
- Limited kidney function (creatinine clearance under 60 ml/min)
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 |
|---|---|---|
| Canakinumab (investigational)Also: ACZ885Canakinumab was supplied in 6 mL colorless glass vials each containing nominally 150 mg canakinumab (with 20% overfill). The vials were kept at 2-8°C. At the investigator's site, solutions for infusion were prepared depending on the volume and dose administered. | Drug | Canakinumab + Methotrexate |
| PlaceboMatching placebo was supplied in form of a lyophilized cake (Powder for Solution for Infusion). At the investigator's site, solutions for infusion were prepared depending on the volume and dose administered. | Drug | Methotrexate + placebo |
| Methotrexate (MTX)Methotrexate (MTX) was supplied in tablet form, each of 2.5 mg strength. | Drug | Canakinumab + Methotrexate, Methotrexate + placebo |
Primary outcome
Response to Intravenous Canakinumab and Oral Methotrexate (MTX) Compared to MTX Alone as Determined by 50% Improvement in Symptoms According to the American College of Rheumatology Criteria (ACR50)
Time frame: 6, 14, and 26 weeks of treatment
A patient was considered as improved according to the ACR50 criteria if she/he had at least a 50 % improvement in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) * Acute phase reactant (high sensitivity C-reactive Protein (hsCRP))
3 secondary outcomes
Response to Intravenous (IV) Canakinumab and Oral Methotrexate (MTX) Therapy (ACR20, 70, 90) Compared to MTX Alone
Time frame: At 6 weeks, 14 weeks, and 26 weeks
Percentage of Participants Achieving a Good European League Against Rheumatism (EULAR) Response (Based on the Disease Activity Score (DAS28)) at 26 Weeks
Time frame: At 26 weeks
The Number of Participants in Clinical Remission Based on Disease Activity Score (DAS)28 and Simplified Disease Activity Index (SDAI)
Time frame: At 6 weeks, 14 weeks and 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2012.
- 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.
Novartis principal investigator
Investigative site
22 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Canakinumab (investigational) and Methotrexate (MTX) in people with Rheumatoid Arthritis, run by Novartis at 22 sites in 6 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 13 inclusion and 18 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 1 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Belgium, Germany, Italy, Netherlands and 1 more country. 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 6 May 2011). 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?
Response to Intravenous Canakinumab and Oral Methotrexate (MTX) Compared to MTX Alone as Determined by 50% Improvement in Symptoms According to the American College of Rheumatology Criteria (ACR50) (time frame: 6, 14, and 26 weeks of treatment). 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 1 Aug 2012.