Rheumatoid ArthritisPhase 3NCT00317538
Open-label, Pilot Protocol of Patients With Rheumatoid Arthritis Who Switch to Infliximab After Incomplete Response to Etanercept
A Phase 3 study testing infliximab, etanercept in people with Rheumatoid Arthritis, run by Centocor Ortho Biotech Services, L.L.C..
Trial summary
The purpose of this study, in patients with rheumatoid arthritis who have had an incomplete response to etanercept and methotrexate (MTX), are to evaluate: safety and evidence of therapeutic benefit of infliximab and methotrexate, the levels (pharmacokinetics) of etanercept and infliximab and antibodies… 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?
- infliximab, etanercept
- How many people
- 28 participants
- Where
- No sites listed yet
- Study dates
- Jun 2003to Nov 2004
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients have a diagnosis of RA according to the revised 1987 criteria of the American Rheumatism Association
- Have been receiving background MTX for at least 2 months prior to week -4
- Have been receiving a stable etanercept dose of 25 mg subcutaneously twice weekly for at least 2 months prior to week -4
- Must have been using oral or parenteral MTX for the 2 months prior to screening and at a stable dose of 7.5 to 25 mg per week between week -4 and week 0
- Have shown improvement in signs and symptoms of RA in response to etanercept and MTX according to both the patient and the treating physician
- Have active disease as defined by both a TJC of at least 9 (on the 68 joint set) and SJC of at least 6 (on the 66 joint set)
- Have a documented negative reaction to a purified protein derivative (PPD) skin test (PPD induration< 5 mm) performed within 3 months prior to the week 0 visit
Who cannot join
- Patients have been receiving corticosteroids (ie, via any route) at doses > 10 mg prednisone equivalent daily or have not been taking a stable dose of corticosteroids for at least 1 month prior to week -4
- Have started receiving nonsteroidal anti-inflammatory drugs (NSAIDs) within 1 month of week -4 or have not been on a stable dose of NSAIDs for at least 1 month prior to week -4
- Have received disease modifying anti-rheumatic drugs (DMARDs) or immunosuppressives (except MTX) for at least 1 month prior to week 0
- Patients who have received any prior treatment with infliximab or with any other therapeutic agent targeted at reducing TNF, except etanercept, (e.g.pentoxifylline or thalidomide)
- Patients with a concomitant diagnosis of Congestive Heart Failure, including medically controlled asymptomatic patients
- Any current known malignancy or history of malignancy within the previous 5 years
Show all 9Show fewer
- Serious infection within the past 3 months or history of chronic infection such as hepatitis, pneumonia, or pyelonephritis in the previous 3 months, any opportunistic infections
- known substance abuse (drug or alcohol) within the previous 3 years
- Are pregnant, nursing, or planning pregnancy (both men and women) during the trial or within the 6-month period thereafter.
About this study
The purpose of this study, in patients with rheumatoid arthritis who have had an incomplete response to etanercept and methotrexate (MTX), are to evaluate: safety and evidence of therapeutic benefit of infliximab and methotrexate, the levels (pharmacokinetics) of etanercept and infliximab and antibodies (immunogenicity) to etanercept and infliximab in patients blood, whether switching from etanercept to infliximab changes progression of structural damage over the study period, and whether specific markers in the blood (pharmacodynamics) correlate with therapeutic response or benefit.
Read the detailed description
Therapeutic agents designed to bind and block the biological activities of tumor necrosis factor-alpha (TNFa) have been shown to be effective in the treatment of rheumatoid arthritis (RA). Two anti-TNFa agents are currently marketed for the treatment of RA; etanercept (Enbrel®) and infliximab (REMICADE®). Clinical trials have shown that both of these agents rapidly improve signs and symptoms associated with RA in the majority of patients. Moreover, they slow, and may even arrest or improve, the joint structural damage that accompanies RA.
While infliximab and etanercept are designed to block the biological activities of TNFa, these agents are sufficiently different in their structure that they may have distinct, as well as overlapping, mechanisms of action. The clearest evidence of this possibility can be inferred from their differential activities in certain diseases such as Crohn's disease in which infliximab, but not etanercept, shows beneficial therapeutic activity. The mechanism of their differential biological activities is not known. That infliximab and etanercept show differential activities in other diseases suggests that they may also have distinct effects in RA.
The question of whether or not patients who fail to respond to or incompletely respond to etanercept can still respond to infliximab has potentially important therapeutic implications. Evidence that such patients respond to infliximab could support the notion that these agents have important differences in their mechanisms of action, or could be explained by the presence of antibodies to etanercept. More importantly, it would suggest that therapeutic failure of one TNFa-blocker does not necessarily predict failure of all TNFa-targeting agents. Such a finding could open important therapeutic alternatives to RA patients and is of clear importance because this class of biologics (biologic agent) represents the most significant advance to date in the treatment of RA.
This initial open-label, pilot study will be performed in approximately 24 patients with RA who have who have achieved some therapeutic benefit from treatment with concomitant etanercept and MTX for a minimum of 3 months, but the response must be an incomplete response, and patients must have a minimum of 9 tender and 6 swollen joints while receiving concomitant etanercept and MTX. It will assess safety and evidence of therapeutic benefit of infliximab in this patient population. The study will examine any differences in the pharmacokinetics and immunogenicity of etanercept and infliximab in patients who are incomplete responders to etanercept.
This is an open-label, exploratory study and no formal hypothesis is being tested. This study will provide a preliminary assessment of safety and evidence of therapeutic benefit of infliximab plus MTX in patients with RA who are incomplete responders to etanercept plus MTX. One group will receive intravenous infliximab infusions at a dose of 3 mg/kg at weeks 0, 2, 6 14 and 22. The second group will receive etanercept injections, 25 mg subcutaneously twice weekly from week 0 through 16 and may receive intravenous infliximab infusions at 3 mg/kg on weeks 16, 18 \& 22.
- Conditions
- Rheumatoid Arthritis
- Being tested
- infliximab, etanercept
- Keywords
- Rheumatoid Arthritis, Switching, Structural Damage, MRI
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
infliximab, etanerceptDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate safety and evidence of therapeutic benefit of infliximab and methotrexate, in patients with rheumatoid arthritis who have had an incomplete response to etanercept and methotrexate (MTX), at week 16
Secondary outcomes (1)
Evaluate pharmacokinetics, immunogenicity, structural damage and pharmacodynamics over the study period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2006 (estimated)
- Study startJun 2003
- Study completionNov 2004
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centocor Ortho Biotech Services, L.L.C.
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Centocor Ortho Biotech Services, L.L.C. Clinical Trial, Study director, Centocor Ortho Biotech Services, L.L.C.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00317538
- Sponsor's protocol ID
- CR003136
- Status last verified
- Apr 2010
- First submitted
- 21 Apr 2006
- Last updated
- 19 May 2011
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Pilot Protocol of Patients With Rheumatoid Arthritis Who Switch to Infliximab After Incomplete Response to Etanercept
- ClinicalTrials.gov ID
- NCT00317538
- Acronym / sponsor ID
- CR003136
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid Arthritis, Switching, Structural Damage, MRI
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Centocor Ortho Biotech Services, L.L.C.Industry (pharma, biotech, devices)
- Study start
- Jun 2003
- Study completion
- Nov 2004 (actual)
- First posted
- 25 Apr 2006 (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.
The purpose of this study, in patients with rheumatoid arthritis who have had an incomplete response to etanercept and methotrexate (MTX), are to evaluate: safety and evidence of therapeutic benefit of infliximab and methotrexate, the levels (pharmacokinetics) of etanercept and infliximab and antibodies (immunogenicity) to etanercept and infliximab in patients blood, whether switching from etanercept to infliximab changes progression of structural damage over the study period, and whether specific markers in the blood (pharmacodynamics) correlate with therapeutic response or benefit.
Detailed description
Therapeutic agents designed to bind and block the biological activities of tumor necrosis factor-alpha (TNFa) have been shown to be effective in the treatment of rheumatoid arthritis (RA). Two anti-TNFa agents are currently marketed for the treatment of RA; etanercept (Enbrel®) and infliximab (REMICADE®). Clinical trials have shown that both of these agents rapidly improve signs and symptoms associated with RA in the majority of patients. Moreover, they slow, and may even arrest or improve, the joint structural damage that accompanies RA.
While infliximab and etanercept are designed to block the biological activities of TNFa, these agents are sufficiently different in their structure that they may have distinct, as well as overlapping, mechanisms of action. The clearest evidence of this possibility can be inferred from their differential activities in certain diseases such as Crohn's disease in which infliximab, but not etanercept, shows beneficial therapeutic activity. The mechanism of their differential biological activities is not known. That infliximab and etanercept show differential activities in other diseases suggests that they may also have distinct effects in RA.
The question of whether or not patients who fail to respond to or incompletely respond to etanercept can still respond to infliximab has potentially important therapeutic implications. Evidence that such patients respond to infliximab could support the notion that these agents have important differences in their mechanisms of action, or could be explained by the presence of antibodies to etanercept. More importantly, it would suggest that therapeutic failure of one TNFa-blocker does not necessarily predict failure of all TNFa-targeting agents. Such a finding could open important therapeutic alternatives to RA patients and is of clear importance because this class of biologics (biologic agent) represents the most significant advance to date in the treatment of RA.
This initial open-label, pilot study will be performed in approximately 24 patients with RA who have who have achieved some therapeutic benefit from treatment with concomitant etanercept and MTX for a minimum of 3 months, but the response must be an incomplete response, and patients must have a minimum of 9 tender and 6 swollen joints while receiving concomitant etanercept and MTX. It will assess safety and evidence of therapeutic benefit of infliximab in this patient population. The study will examine any differences in the pharmacokinetics and immunogenicity of etanercept and infliximab in patients who are incomplete responders to etanercept.
This is an open-label, exploratory study and no formal hypothesis is being tested. This study will provide a preliminary assessment of safety and evidence of therapeutic benefit of infliximab plus MTX in patients with RA who are incomplete responders to etanercept plus MTX. One group will receive intravenous infliximab infusions at a dose of 3 mg/kg at weeks 0, 2, 6 14 and 22. The second group will receive etanercept injections, 25 mg subcutaneously twice weekly from week 0 through 16 and may receive intravenous infliximab infusions at 3 mg/kg on weeks 16, 18 \& 22.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients have a diagnosis of RA according to the revised 1987 criteria of the American Rheumatism Association
- Have been receiving background MTX for at least 2 months prior to week -4
- Have been receiving a stable etanercept dose of 25 mg subcutaneously twice weekly for at least 2 months prior to week -4
- Must have been using oral or parenteral MTX for the 2 months prior to screening and at a stable dose of 7.5 to 25 mg per week between week -4 and week 0
- Have shown improvement in signs and symptoms of RA in response to etanercept and MTX according to both the patient and the treating physician
Key exclusion criteria (9 listed)
- Patients have been receiving corticosteroids (ie, via any route) at doses > 10 mg prednisone equivalent daily or have not been taking a stable dose of corticosteroids for at least 1 month prior to week -4
- Have started receiving nonsteroidal anti-inflammatory drugs (NSAIDs) within 1 month of week -4 or have not been on a stable dose of NSAIDs for at least 1 month prior to week -4
- Have received disease modifying anti-rheumatic drugs (DMARDs) or immunosuppressives (except MTX) for at least 1 month prior to week 0
- Patients who have received any prior treatment with infliximab or with any other therapeutic agent targeted at reducing TNF, except etanercept, (e.g.pentoxifylline or thalidomide)
- Patients with a concomitant diagnosis of Congestive Heart Failure, including medically controlled asymptomatic patients
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 |
|---|---|---|
| infliximab, etanercept | Drug | – |
Primary outcome
Evaluate safety and evidence of therapeutic benefit of infliximab and methotrexate, in patients with rheumatoid arthritis who have had an incomplete response to etanercept and methotrexate (MTX), at week 16
1 secondary outcome
Evaluate pharmacokinetics, immunogenicity, structural damage and pharmacodynamics over the study period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2011.
- Open-label, Pilot Protocol of Patients with Rheumatoid Arthritis Who Switch to Infliximab after Incomplete Response to EtanerceptLink provided by the sponsor.
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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.
Centocor Ortho Biotech Services, L.L.C. Clinical Trial study director
Centocor Ortho Biotech Services, L.L.C.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing infliximab, etanercept in people with Rheumatoid Arthritis, run by Centocor Ortho Biotech Services, L.L.C..
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 7 inclusion and 9 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 19 May 2011. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Evaluate safety and evidence of therapeutic benefit of infliximab and methotrexate, in patients with rheumatoid arthritis who have had an incomplete response to etanercept and methotrexate (MTX), at week 16. 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 19 May 2011.