Rheumatoid ArthritisPhase 1/2NCT00505089
Efficacy and Safety of Subcutaneous Versus Intravenous ACZ885 in Adult Patients With Established Rheumatoid Arthritis
A Phase 1/2 study testing ACZ885 in people with Rheumatoid Arthritis, run by Novartis at 9 sites in 4 countries.
Trial summary
This study will investigate the pharmacokinetic (PK) / total IL-1beta pharmacodynamic (PD) relationship in joint fluids of patients with rheumatoid arthritis (RA) treated with different doses of ACZ885 and to evaluate the impact of the subcutaneous (s.c.) versus intravenous (i.v.) route of administration. 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?
- ACZ885
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 9 sitesin 4 countries
- Study dates
- Aug 2007to May 2009
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 aged 18 - 75 years (inclusive).
- Body weight must be between 50 and 100 kg (inclusive).
- Post-menopausal or surgically sterile female patients. Women of child-bearing potential if already on a stable dose of methotrexate and are practicing effective contraception for at least 3 months prior to screening, have a negative pregnancy test at screening and baseline, and are willing to use 2 forms of contraception including at least 1 barrier method during the study and for at least 2 months following the completion/discontinuation of the study. Male patients must be willing to use an effective contraception method during the study and at least for 2 months following the completion/discontinuation of the study.
- Diagnosis of Rheumatoid Arthritis, classified by ARA (American Rheumatism Association) 1987 revised criteria (Appendix 2). Disease duration of at least 6 months prior to randomization is essential.
- Functional status class I, II or III classified according to the ACR (American College of Rheumatology) 1991 revised criteria (Appendix 3).
- Active disease at screening and baseline (Day 1 predose) evaluation (same evaluator): ≥ 6 tender and ≥ 6 swollen joints of 28 examined (including any effused joint) and either a) Westergren erythrocyte sedimentation rate (ESR) ≥ 28 mm/hour, or b) C-reactive protein (CRP) ≥ 1.0 mg/dL.
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- 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". Patients should be on a current treatment with methotrexate ≤ 25 mg/week and with the current dose stable for at least 3 months. 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).
- Patients with a total white cell count and platelet count clinically acceptable for patients with RA; hemoglobin must be ≥ 10 g/dL and hematocrit ≥ 30% at screening and baseline.
Who cannot join
- Previous treatment with anti-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.
- If patient has been discontinued from other DMARDs for lack of efficacy or toxicity, the patient should be at least 1 month off the agent and the effects of that agent should have dissipated according to the recognized duration of effect (e.g., sulfasalazine, hydroxychloroquine), or standard washout procedure (cholestyramine for leflunomide). Importantly, discontinuation should not be undertaken only for the purposes of participation in this study.
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- 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 four weeks prior to randomization.
- Presence of or history of Major chronic inflammatory autoimmune diseases like psoriasis, psoriatic arthritis, spondyloarthropathy, inflammatory bowel disease or systemic lupus erythematosus.
- Renal trauma, glomerulonephritis or patient with one kidney. Patients with congestive heart failure (New York Heart Association class > III), QT prolongation syndrome or poorly controlled diabetes mellitus. Patients with a history of QTc prolongation will be excluded. A positive HIV test result, Hepatitis B surface antigen or Hepatitis C test result. Significant illness within 2 weeks prior to dosing or any active systemic infection or medical condition that may require treatment or therapeutic intervention during the study. Hypersensitivity to any biological agents, serious allergic reaction, collagen disease, neurological disease (including demyelinating disease). Any joint surgery in past 8 weeks or planned surgery within next 5 months. Cancer (other than basal cell cancer or adequately treated carcinoma-in-situ of the cervix). Drug or alcohol abuse within the 12 months prior to dosing or evidence of such indicated by the laboratory assays conducted during the screening or baseline evaluations. Underlying metabolic, endocrine, hematologic, pulmonary, cardiac, blood, renal, hepatic, infectious, psychiatric or gastrointestinal conditions which places the patient at unacceptable risk for participation in a study of an immunomodulatory therapy.
- Treatment with an investigational agent within 12 weeks prior to enrollment or longer if required by local regulation.
- Pregnant or breastfeeding women.
- Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
9 sites in 4 countries.
9 sites in 4 countries
Germany4 sites
Novartis Investigative site
Berlin
Novartis Investigator Site
Berlin
Novartis Investigator Site
Hanover
Novartis Investigator Site
Leipzig
Belgium2 sites
Novartis Investigative site
Antwerp
Novartis Investigator Site
Liège
Poland2 sites
Novartis Investigative Site
Grodzisk Mazowiecki
Novartis Investigator Site
Poznan
About this study
Official title: An Exploratory, Open Label Pharmacokinetic - Pharmacodynamic Study to Compare Subcutaneous Versus Intravenous Administration of ACZ885 in Adult Patients With Established Rheumatoid Arthritis
This study will investigate the pharmacokinetic (PK) / total IL-1beta pharmacodynamic (PD) relationship in joint fluids of patients with rheumatoid arthritis (RA) treated with different doses of ACZ885 and to evaluate the impact of the subcutaneous (s.c.) versus intravenous (i.v.) route of administration.
- Conditions
- Rheumatoid Arthritis
- Being tested
- ACZ885
- Keywords
- pharmacokinetic, pharmacodynamic, subcutaneous, intravenous, ACZ885, patients, rheumatoid, 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.
ACZ885Drug
ACZ885Drug
ACZ885Drug
ACZ885Drug
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | ACZ885 10mg/kg subcutaneous Receives: Drug: ACZ885 |
| 2 | Experimental | ACZ885 5mg/kg intravenous Receives: Drug: ACZ885 |
| 3 | Experimental | ACZ885 2mg/kg subcutaneous Receives: Drug: ACZ885 |
| 4 | Experimental | ACZ885 1mg/kg intravenous Receives: Drug: ACZ885 |
What is being measured
The primary outcome is the main question the study is designed to answer.
- Pharmacokinetic/total IL-1beta pharmacodynamic relationship in joint fluids of patients with rheumatoid arthritis treated with different doses of ACZ885 - Impact of the subcutaneous versus intravenous administration
Measured: End of study
Secondary outcomes (1)
- PK/PD of ACZ885 in patient serum and to evaluate impact of s.c. versus i.v. administration - Efficacy via response to treatment (ACR 20% improvement [ACR 20],50,70 & 90)
Measured: Days 8,15,29,43 and study completion
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 startAug 2007
- Primary completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Novartis, Principal investigator, Investigative site
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00505089
- Sponsor's protocol ID
- CACZ885A2206
- Status last verified
- Aug 2009
- First submitted
- 19 Jul 2007
- Last updated
- 25 Aug 2009
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory, Open Label Pharmacokinetic - Pharmacodynamic Study to Compare Subcutaneous Versus Intravenous Administration of ACZ885 in Adult Patients With Established Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT00505089
- Acronym / sponsor ID
- CACZ885A2206
- Conditions
- Rheumatoid Arthritis
- Keywords
- pharmacokinetic, pharmacodynamic, subcutaneous, intravenous, ACZ885, patients, rheumatoid, arthritis.
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 11 participants (actual)
- Lead sponsor
- NovartisIndustry (pharma, biotech, devices)
- Study start
- Aug 2007
- Primary completion
- May 2009 (actual)
- First posted
- 20 Jul 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will investigate the pharmacokinetic (PK) / total IL-1beta pharmacodynamic (PD) relationship in joint fluids of patients with rheumatoid arthritis (RA) treated with different doses of ACZ885 and to evaluate the impact of the subcutaneous (s.c.) versus intravenous (i.v.) route of administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: ACZ885ACZ885 10mg/kg subcutaneous |
| 2 | Experimental | Drug: ACZ885ACZ885 5mg/kg intravenous |
| 3 | Experimental | Drug: ACZ885ACZ885 2mg/kg subcutaneous |
| 4 | Experimental | Drug: ACZ885ACZ885 1mg/kg intravenous |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male and female patients aged 18 - 75 years (inclusive).
- Body weight must be between 50 and 100 kg (inclusive).
- Post-menopausal or surgically sterile female patients. Women of child-bearing potential if already on a stable dose of methotrexate and are practicing effective contraception for at least 3 months prior to screening, have a negative pregnancy test at screening and baseline, and are willing to use 2 forms of contraception including at least 1 barrier method during the study and for at least 2 months following the completion/discontinuation of the study. Male patients must be willing to use an effective contraception method during the study and at least for 2 months following the completion/discontinuation of the study.
- Diagnosis of Rheumatoid Arthritis, classified by ARA (American Rheumatism Association) 1987 revised criteria (Appendix 2). Disease duration of at least 6 months prior to randomization is essential.
- Functional status class I, II or III classified according to the ACR (American College of Rheumatology) 1991 revised criteria (Appendix 3).
Key exclusion criteria (13 listed)
- Previous treatment with anti-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 for lack of efficacy or toxicity, the patient should be at least 1 month off the agent and the effects of that agent should have dissipated according to the recognized duration of effect (e.g., sulfasalazine, hydroxychloroquine), or standard washout procedure (cholestyramine for leflunomide). Importantly, discontinuation should not be undertaken only for the purposes of participation in this study.
- 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 four weeks prior to randomization.
- Presence of or history of Major chronic inflammatory autoimmune diseases like psoriasis, psoriatic arthritis, spondyloarthropathy, inflammatory bowel disease or systemic lupus erythematosus.
- Renal trauma, glomerulonephritis or patient with one kidney. Patients with congestive heart failure (New York Heart Association class > III), QT prolongation syndrome or poorly controlled diabetes mellitus. Patients with a history of QTc prolongation will be excluded. A positive HIV test result, Hepatitis B surface antigen or Hepatitis C test result. Significant illness within 2 weeks prior to dosing or any active systemic infection or medical condition that may require treatment or therapeutic intervention during the study. Hypersensitivity to any biological agents, serious allergic reaction, collagen disease, neurological disease (including demyelinating disease). Any joint surgery in past 8 weeks or planned surgery within next 5 months. Cancer (other than basal cell cancer or adequately treated carcinoma-in-situ of the cervix). Drug or alcohol abuse within the 12 months prior to dosing or evidence of such indicated by the laboratory assays conducted during the screening or baseline evaluations. Underlying metabolic, endocrine, hematologic, pulmonary, cardiac, blood, renal, hepatic, infectious, psychiatric or gastrointestinal conditions which places the patient at unacceptable risk for participation in a study of an immunomodulatory therapy.
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 | Drug | 1 |
| ACZ885 | Drug | 2 |
| ACZ885 | Drug | 3 |
| ACZ885 | Drug | 4 |
Primary outcome
- Pharmacokinetic/total IL-1beta pharmacodynamic relationship in joint fluids of patients with rheumatoid arthritis treated with different doses of ACZ885 - Impact of the subcutaneous versus intravenous administration
Time frame: End of study
1 secondary outcome
- PK/PD of ACZ885 in patient serum and to evaluate impact of s.c. versus i.v. administration - Efficacy via response to treatment (ACR 20% improvement [ACR 20],50,70 & 90)
Time frame: Days 8,15,29,43 and study completion
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2009.
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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
9 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ACZ885 in people with Rheumatoid Arthritis, run by Novartis at 9 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 13 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: stopped early, as of the sponsor's last update on 25 Aug 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Germany, Belgium, Poland, Netherlands. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study was stopped early. Results are not available in the source record.
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?
- Pharmacokinetic/total IL-1beta pharmacodynamic relationship in joint fluids of patients with rheumatoid arthritis treated with different doses of ACZ885 - Impact of the subcutaneous versus intravenous administration (time frame: End of study). 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 25 Aug 2009.