Rheumatoid ArthritisPhase 2NCT00504595
Safety and Efficacy of ACZ885 in Adult Patients With Established Rheumatoid Arthritis
A Phase 2 study testing ACZ885 (investigational) in people with Rheumatoid Arthritis, run by Novartis at 4 sites in 4 countries.
Trial summary
This study was intended to assess the safety, efficacy, and response to treatment using the American College of Rheumatology (ACR) criteria of 20% improvement in symptoms (ACR20) and to investigate a potential biomarker profile in adult patients with established rheumatoid arthritis Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- ACZ885 (investigational)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 4 sitesin 4 countries
- Study dates
- May 2007to Sep 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- RA patients:
- Male and female patients aged 18 - 75 years (inclusive).
- Body weight between 50 and 100 kg (inclusive).
- Post menopausal or surgically sterile female patients are allowed. Female patients of child-bearing potential may participate if they are already on a stable dose of methotrexate. Additional birth control details to be provided at screening. Male patients must use an effective contraception method during the study and at least for 2 months following the completion/discontinuation of the study.
- Diagnosis of RA, classified by American Rheumatism Association 1987 revised criteria. Disease duration of at least 6 months is essential.
- Functional status class I, II or III classified according to the American College of Rheumatology 1991 revised criteria.
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- Active disease evaluation (≥ 6 tender and ≥ 6 swollen joints)
- Prior treatment with 1-3 disease-modifying anti-rheumatic drugs (DMARDs) - Patients should have failed at least 1 DMARD but should not be deemed "refractory to all therapies". It is expected that patients are on a current treatment with methotrexate ≤ 25 mg/week and with the current dose stable for at least 3 months, however patients who did not tolerate MTX may also be considered. All patients will take folic acid 1 mg daily, or 5 mg weekly post MTX dose, to minimize toxicity, according to local guidelines. In addition to methotrexate, patients may be on either a stable dose of non-steroidal anti-inflammatory drugs (NSAIDs) and/or a stable dose of oral corticosteroids (prednisone or equivalent ≤ 10 mg daily) for at least 4 weeks prior to randomization. Patients who failed any DMARDs will be allowed.
- Negative purified protein derivative (PPD) tuberculin skin test reaction (PPD 5 tuberculin units or as according to local standard practice).
Who cannot join
- RA patients:
- Previous treatment with anti-Tumor Necrosis Factor (TNF)-α or anti IL-1 therapy (or other biological therapy), immunosuppressive agents such as cyclosporine, mycophenolate or tacrolimus. The following washout period will be required for such patients to be eligible to participate in the trial.
- 2 months washout prior to screening for etanercept or adalimumab
- 3 months washout prior to screening for infliximab
- 3 months washout prior to screening for rituximab
- 1 month washout prior to screening for cyclosporine, mycophenolate and tacrolimus.
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- If patient has been discontinued from other DMARDs (disease modifying antirheumatic drugs) for lack of efficacy or toxicity, the patient should be at least 1 month off the agent.
- Patients with congestive heart failure, QT prolongation syndrome or poorly controlled diabetes mellitus. Patients with a history of QTc prolongation will be excluded.
- Patients who have received intra-articular or systemic corticosteroid injections having been required for treatment of acute RA flare (not being part of a regular therapeutic regimen) within 4 weeks prior to randomization.
- Exclusion criteria 2-6 of the Health Volunteer section also applies here.
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
About this study
Official title: A 12-week, Phase II, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Assess the Response to Treatment (ACR20) and to Determine a Biomarker Profile in Adult Patients With Established Rheumatoid Arthritis Responding to ACZ885 (Anti-interleukin-1beta Monoclonal Antibody) as Compared to Healthy Subjects Exposed to ACZ885
This study was intended to assess the safety, efficacy, and response to treatment using the American College of Rheumatology (ACR) criteria of 20% improvement in symptoms (ACR20) and to investigate a potential biomarker profile in adult patients with established rheumatoid arthritis
- Conditions
- Rheumatoid Arthritis
- Being tested
- ACZ885 (investigational), Placebo
- Keywords
- Rheumatoid Arthritis
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACZ885 (investigational)Drug
Also called Canakinumab
The ACZ885 was supplied in 6 mL colorless glass vials each containing nominally 150 mg ACZ885 (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 of ACZ885 was supplied in the 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.
| Study group | Role | What they receive |
|---|---|---|
| ACZ885 | Experimental | Healthy Volunteers: Single administration of 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1.
Rheumatoid Arthritis (RA) Patients: Dose of 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1, Day 15, and Day 43. Receives: Drug: ACZ885 (investigational) |
| Placebo | Placebo comparator | Healthy Volunteers: Single administration of 600 mg of Placebo Intravenous (IV) on Day 1.
Rheumatoid Arthritis (RA) Patients: Dose of 600 mg of Placebo Intravenous (IV) on Day 1, Day 15, and Day 43. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response to Treatment (ACR20) in Adult Patients With Established Rheumatoid Arthritis (RA)
At each post-dose visit, an ACR20 responder was defined as someone who achieved at least 20% improvement in the tender and the swollen 28-joint count, and 20% improvement 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 weeks and 12 weeks
Secondary outcomes (2)
Efficacy of ACZ885 by Assessing the Response to Treatment Using the Simple Disease Index (SDAI)
SDAI is derived by the number of swollen joints and tender joints using the 28-joint count (tender28 and swollen28). SDAI measures the high sensitivity C-reactive protein (hsCRP) level, patient's global disease activity (PGDA) and evaluator's global disease activity (EGDA). PGDA and EGDA are measured on a 100 mm Visual Analogue Scale (VAS), ranging from no arthritis activity to maximal arthritis activity. SDAI = tender28 + swollen28 + CRP + (PGDA/10) + (EGDA/10). Lower scores indicate less disease activity.
Measured: 6 weeks and 12 weeks
Efficacy of ACZ885 (Canakinumab) by Assessing the Response to Treatment Using the Disease Activity Score (DAS28)
DAS28 is derived by the number of swollen joints and tender joints using the 28-joint count (tender28 and swollen28). DAS28 measures the C-reactive protein (CRP) (in mg/L) and the patient's general health (GH). GH is measured on a 100 mm Visual Analogue Scale (VAS), ranging from no arthritis activity to maximal arthritis activity. DAS28 = 0.56*√(tender28) + 0.28*√(swollen28) + 0.36*log_e(CRP+1) + 0.014*PGDA + 0.96. Lower scores indicate less disease activity.
Measured: 6 weeks and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2007 (estimated)
- Study startMay 2007
- Primary completionSep 2008
- Study completionSep 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
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis, Principal investigator, Investigator site
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00504595
- Sponsor's protocol ID
- CACZ885A2207
- Status last verified
- Aug 2012
- First submitted
- 19 Jul 2007
- Last updated
- 7 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 7 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 12-week, Phase II, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Assess the Response to Treatment (ACR20) and to Determine a Biomarker Profile in Adult Patients With Established Rheumatoid Arthritis Responding to ACZ885 (Anti-interleukin-1beta Monoclonal Antibody) as Compared to Healthy Subjects Exposed to ACZ885
- ClinicalTrials.gov ID
- NCT00504595
- Acronym / sponsor ID
- CACZ885A2207
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid Arthritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- NovartisIndustry (pharma, biotech, devices)
- Study start
- May 2007
- Primary completion
- Sep 2008 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 20 Jul 2007 (estimated)
- Results
- Posted 23 Jun 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 assess the safety, efficacy, and response to treatment using the American College of Rheumatology (ACR) criteria of 20% improvement in symptoms (ACR20) and to investigate a potential biomarker profile in adult patients with established rheumatoid arthritis
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 |
|---|---|---|
| ACZ885 | Experimental | Drug: ACZ885 (investigational)Healthy Volunteers: Single administration of 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1. Rheumatoid Arthritis (RA) Patients: Dose of 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1, Day 15, and Day 43. |
| Placebo | Placebo comparator | Drug: PlaceboHealthy Volunteers: Single administration of 600 mg of Placebo Intravenous (IV) on Day 1. Rheumatoid Arthritis (RA) Patients: Dose of 600 mg of Placebo Intravenous (IV) on Day 1, Day 15, and Day 43. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male and female patients aged 18 - 75 years (inclusive).
- Body weight between 50 and 100 kg (inclusive).
- Post menopausal or surgically sterile female patients are allowed. Female patients of child-bearing potential may participate if they are already on a stable dose of methotrexate. Additional birth control details to be provided at screening. Male patients must use an effective contraception method during the study and at least for 2 months following the completion/discontinuation of the study.
- Diagnosis of RA, classified by American Rheumatism Association 1987 revised criteria. Disease duration of at least 6 months is essential.
- Functional status class I, II or III classified according to the American College of Rheumatology 1991 revised criteria.
Key exclusion criteria (11 listed)
- Previous treatment with anti-Tumor Necrosis Factor (TNF)-α or anti IL-1 therapy (or other biological therapy), immunosuppressive agents such as cyclosporine, mycophenolate or tacrolimus. The following washout period will be required for such patients to be eligible to participate in the trial.
- If patient has been discontinued from other DMARDs (disease modifying antirheumatic drugs) for lack of efficacy or toxicity, the patient should be at least 1 month off the agent.
- Patients with congestive heart failure, QT prolongation syndrome or poorly controlled diabetes mellitus. Patients with a history of QTc prolongation will be excluded.
- Patients who have received intra-articular or systemic corticosteroid injections having been required for treatment of acute RA flare (not being part of a regular therapeutic regimen) within 4 weeks prior to randomization.
- Exclusion criteria 2-6 of the Health Volunteer section also applies here.
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 |
|---|---|---|
| ACZ885 (investigational)Also: CanakinumabThe ACZ885 was supplied in 6 mL colorless glass vials each containing nominally 150 mg ACZ885 (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 | ACZ885 |
| PlaceboMatching placebo of ACZ885 was supplied in the 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 | Placebo |
Primary outcome
Response to Treatment (ACR20) in Adult Patients With Established Rheumatoid Arthritis (RA)
Time frame: 6 weeks and 12 weeks
At each post-dose visit, an ACR20 responder was defined as someone who achieved at least 20% improvement in the tender and the swollen 28-joint count, and 20% improvement 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))
2 secondary outcomes
Efficacy of ACZ885 by Assessing the Response to Treatment Using the Simple Disease Index (SDAI)
Time frame: 6 weeks and 12 weeks
Efficacy of ACZ885 (Canakinumab) by Assessing the Response to Treatment Using the Disease Activity Score (DAS28)
Time frame: 6 weeks and 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 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
Investigator site
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ACZ885 (investigational) in people with Rheumatoid Arthritis, run by Novartis at 4 sites in 4 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 9 inclusion and 11 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 7 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 4 sites in Russia, Spain, Switzerland, Turkey (Türkiye). 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 23 Jun 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 Treatment (ACR20) in Adult Patients With Established Rheumatoid Arthritis (RA) (time frame: 6 weeks and 12 weeks). 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 7 Aug 2012.