Rheumatoid ArthritisPhase 2RA-1NCT00221000
Safety and Efficacy of Extracorporeal Photoimmune Therapy With UVADEX for the Treatment of Rheumatoid Arthritis
A Phase 2 study testing Methoxsalen and Extracorporeal Photopheresis in people with Rheumatoid Arthritis, run by Mallinckrodt at 32 sites in 11 countries.
Trial summary
Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disorder that can cause substantial pain and joint tenderness, significant joint damage, and serious disability. The treatment goals are minimization of the signs and symptoms of the disease, and the reduction of irreversible joint damage. 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?
- Methoxsalen and Extracorporeal Photopheresis
- Type of treatment
- Surgery or procedure
- How many people
- 86 participants
- Where
- 32 sitesin 11 countries
- Study dates
- Aug 2003to Nov 2006
- Phase
- Phase 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have a history of RA per the ACR criteria for the classification of RA.
- Patients must have moderately to severely active RA.
- Moderately to severely active RA patients are defined as those patients meeting the following classification criteria, upon review by a physician, during screening: At least nine tender joints; At least six swollen joints;
- PLUS (at least one of the following):
- Morning stiffness, lasting greater than or equal to 45 minutes; Erythrocyte Sedimentation Rate greater than or equal to 28 mm/hour (ESR, to be evaluated at a local laboratory) or C reactive protein (CRP) greater than or equal to 15 mg/dL (to be evaluated at a central laboratory).
- Patients must have an inadequate response and continue to have moderately to severely active disease while on current or previous treatment with at least one agent from both of the following groups: methotrexate (greater than or equal to 15 mg/week, or maximum tolerated dose) or leflunomide (20 mg/day, or maximum tolerated dose) for at least 12 weeks prior to screening; etanercept ( greater than or equal to 25 mg/2 x week SC, or maximum tolerated dose) for at least 12 weeks prior to screening, infliximab (greater than or equal to 3 mg/kg IV, or maximum tolerated dose) for at least 14 weeks duration prior to screening, or adalimumab (greater than or equal to 40 mg SC every 2 weeks, or maximum tolerated dose) for at least 12 weeks prior to screening.
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- Note: In individual cases or in a country where access to anti TNF agents is limited or anti TNF agents are unavailable, the Investigator should document the reason for lack of availability of this treatment. Those patients who have not been treated with an anti-TNF agent would still be eligible for the study if they have failed treatment with at least two additional DMARDs, besides MTX and/or leflunomide. All patients may have also failed treatment with other biological agents or a protein A column.
- Patients who are not on oral corticosteroids. OR Patients who have been on a stable dose of oral corticosteroids at a prednisone equivalent dosage greater than or equal to 15 mg/day for at least 4 weeks prior to screening.
- Patients must have a platelet count greater than or equal to 100,000/cmm.
- Female patients must be one of the following: postmenopausal, surgically incapable of bearing children, practicing an acceptable method of birth control (acceptable methods may include hormonal contraceptives, intrauterine device, and spermicide and barrier). Abstinence or partner/spouse sterility may also qualify at the Investigator's discretion. If a female patient is of childbearing potential, she must have a negative urine pregnancy test at screening.
- Patients must be able and willing to comply with all study procedures.
- Patients must be willing to sign an ICF.
- Patients must be greater than or equal to 18 years of age.
- Patients must have a body weight greater than or equal to 40 kg (88 lb).
Who cannot join
- Patients who have a form of arthritis or arthropathy, other than RA, or any current inflammatory condition that might confound the assessments (e.g., other connective tissue diseases or Lyme disease).
- Patients who have been enrolled in any investigational therapy study for the treatment of RA within 4 weeks prior to the start of the Treatment Period, or patients who are scheduled to receive investigational therapies or a plasma based apheresis procedure (e.g., a protein A column) for the treatment of RA during the course of the study.
- Patients unable to tolerate the extracorporeal volume shifts associated with ECP treatment due to the presence of any of the following conditions: uncompensated congestive heart failure, pulmonary edema, severe chronic obstructive pulmonary disease, severe asthma, renal failure, or hepatic failure.
- Patients with a poor tolerability of venipuncture or a lack of adequate venous access for required treatments and blood sampling.
- Note: Every attempt should be made to enroll patients who have adequate peripheral venous access.
- Patients who have a known hypersensitivity or allergy to psoralen (methoxsalen).
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- Patients who have a known hypersensitivity or allergy to both heparin and citrate products.
- Patients who are taking any of the following permitted DMARDs and biological agents and have not been on a stable dose for the specific indicated periods of time prior to screening: MTX for at least 8 weeks; leflunomide for at least 8 weeks; infliximab for at least 14 weeks; etanercept for at least 12 weeks; adalimumab for at least 12 weeks.
- Patients who are taking any of the following permitted medications and have not been on a stable dose for at least 4 weeks prior to screening: NSAIDs; anakinra; hydroxychloroquine; chloroquine; sulfasalazine; D-penicillamine; gold salts; azathioprine; oral corticosteroids (greater than or equal to 15 mg/day, prednisone equivalent dose).
- Patients whom the Investigator believes cannot be maintained on stable doses of permitted concomitant RA medications throughout the Treatment Period.
- Patients who are taking any of the following prohibited medications: cyclophosphamide; chlorambucil; intramuscular (IM) or intravenous (IV) corticosteroid injection(s), within 4 weeks of screening; intra-articular corticosteroid injection(s) > 60 mg prednisone equivalent total dose, within 4 weeks of screening.
- Patients who have any known malignant disease (other than basal cell carcinoma) currently or within the last 5 years.
- Patients who have a pre-existing blood dyscrasia such as bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia, or a coagulation disorder.
- Patients with a persistent or severe infection within 12 weeks of screening.
- Patients with a history of drug or alcohol abuse within 12 weeks of screening.
- Patients with impaired hepatic function at screening as shown by abnormal liver function tests (LFT; i.e., aspartate transaminase [AST] or alanine transaminase [ALT] levels > 2 x the upper limit of normal [ULN]).
- Women who are pregnant or lactating.
Trial locations and contacts
32 sites in 11 countries.
32 sites in 11 countries
United States10 sites
UT Southwestern Medical Center
Dallas, Texas
Morristown Memorial Hospital
Morristown, New Jersey
Rheumatology Associates
Providence, Rhode Island
AAIR Research Center
Rochester, New York
Arthritis and Osteoporosis Center of South Texas
San Antonio, Texas
Benaroya Research Institute at Virginia Mason
Seattle, Washington
Carroll County Arthritis and Osteoporosis Center
Westminister, Maryland
Rheumatic Disease Associates
Willow Grove, Pennsylvania
Carolina Arthritis Associates
Wilmington, North Carolina
Clinical Pharmacology Study Group
Worchester, Massachusetts
Germany7 sites
Franz von Prummer Klinik
Bad Brückenau
University of Charite Clinic for Rheumatology and Immunology
Berlin
Klinikum der Universitat zu Koln
Cologne
Medizinische Klinik III
Erlangen
Abt. Rheumatologie und Klinische Immunologie
Hamburg
Westfalische wilhelms-universitat Munster
Münster
Medizinische Klinik des Evangelischen Kranken
Oldenburg
Italy3 sites
Universita degli Studi di Firenze
Florence
Universita de Genova - Ospedale S. Martino
Genova
University of Siena-Italy
Siena
South Africa3 sites
South African National Blood Service
Bloemfontein
Christian Barnard Mermorial Hospital
Cape Town
D6 Rheumatology Clinic and E5 Hematology Unit
Cape Town
Belgium2 sites
Hospital Brugmann
Brussels
Limburgs Universitair Centrum
Diepenbeek
About this study
Official title: A Phase II, Multicenter, Randomized, Double-blind, "Sham" Pheresis-controlled, Study of Extracorporeal Photoimmune Therapy With UVADEX for the Treatment of Rheumatoid Arthritis in Patients Who Have an Inadequate Response to Disease Modifying Antirheumatic Drugs and Biological Agents
Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disorder that can cause substantial pain and joint tenderness, significant joint damage, and serious disability. The treatment goals are minimization of the signs and symptoms of the disease, and the reduction of irreversible joint damage.
As the understanding of the pathophysiological mechanisms underlying RA is elucidated, the opportunity to target specific inflammatory processes with new therapies has improved. Rheumatoid arthritis is a T cell-mediated autoimmune disease and there are various therapies, including newer experimental therapies, which target either the activation of T cells or the neutralization of their effector mechanisms. These newer therapies have shown benefit in human and animal models of RA. Extracorporeal photoimmune therapy (ECP) has been shown to be safe and effective in the palliative treatment of the skin manifestations of cutaneous T cell lymphoma. Experimental studies have also demonstrated activity of ECP treatment in several T cell mediated diseases including graft versus-host disease, rejection after organ transplantation, and selected autoimmune diseases.
This study will evaluate a cell-based therapy (ECP) in patients who have an inadequate response to disease-modifying antirheumatic drugs (DMARDs) and biological agents to determine if ECP treatment can reduce the signs and symptoms of RA in this refractory patient population.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Methoxsalen, Extracorporeal Photopheresis
- 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.
MethoxsalenDrug
Extracorporeal PhotopheresisProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
ACR 20
At least a 20% improvement of ACR 20 from baseline
Measured: week 24 and week 28
Secondary outcomes (1)
ACR 50
Improvement of at least 50% from baseline on ACR 50
Measured: week 24 and week 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startAug 2003
- Primary completionOct 2006
- Study completionNov 2006
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mallinckrodt
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- EDWARD KEYSTONE, MD, Principal investigator, Rebecca MacDonald Centre for Arthritis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00221000
- Sponsor's protocol ID
- RA-1
- Acronym
- RA-1
- Status last verified
- Oct 2016
- First submitted
- 13 Sep 2005
- Last updated
- 19 Oct 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Multicenter, Randomized, Double-blind, "Sham" Pheresis-controlled, Study of Extracorporeal Photoimmune Therapy With UVADEX for the Treatment of Rheumatoid Arthritis in Patients Who Have an Inadequate Response to Disease Modifying Antirheumatic Drugs and Biological Agents
- ClinicalTrials.gov ID
- NCT00221000
- Acronym / sponsor ID
- RA-1 / RA-1
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid Arthritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- MallinckrodtIndustry (pharma, biotech, devices)
- Study start
- Aug 2003
- Primary completion
- Oct 2006 (actual)
- Study completion
- Nov 2006 (actual)
- First posted
- 22 Sep 2005 (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.
Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disorder that can cause substantial pain and joint tenderness, significant joint damage, and serious disability. The treatment goals are minimization of the signs and symptoms of the disease, and the reduction of irreversible joint damage.
As the understanding of the pathophysiological mechanisms underlying RA is elucidated, the opportunity to target specific inflammatory processes with new therapies has improved. Rheumatoid arthritis is a T cell-mediated autoimmune disease and there are various therapies, including newer experimental therapies, which target either the activation of T cells or the neutralization of their effector mechanisms. These newer therapies have shown benefit in human and animal models of RA. Extracorporeal photoimmune therapy (ECP) has been shown to be safe and effective in the palliative treatment of the skin manifestations of cutaneous T cell lymphoma. Experimental studies have also demonstrated activity of ECP treatment in several T cell mediated diseases including graft versus-host disease, rejection after organ transplantation, and selected autoimmune diseases.
This study will evaluate a cell-based therapy (ECP) in patients who have an inadequate response to disease-modifying antirheumatic drugs (DMARDs) and biological agents to determine if ECP treatment can reduce the signs and symptoms of RA in this refractory patient population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients must have a history of RA per the ACR criteria for the classification of RA.
- Patients must have moderately to severely active RA.
- Moderately to severely active RA patients are defined as those patients meeting the following classification criteria, upon review by a physician, during screening: At least nine tender joints; At least six swollen joints;
- Morning stiffness, lasting greater than or equal to 45 minutes; Erythrocyte Sedimentation Rate greater than or equal to 28 mm/hour (ESR, to be evaluated at a local laboratory) or C reactive protein (CRP) greater than or equal to 15 mg/dL (to be evaluated at a central laboratory).
- Patients must have an inadequate response and continue to have moderately to severely active disease while on current or previous treatment with at least one agent from both of the following groups: methotrexate (greater than or equal to 15 mg/week, or maximum tolerated dose) or leflunomide (20 mg/day, or maximum tolerated dose) for at least 12 weeks prior to screening; etanercept ( greater than or equal to 25 mg/2 x week SC, or maximum tolerated dose) for at least 12 weeks prior to screening, infliximab (greater than or equal to 3 mg/kg IV, or maximum tolerated dose) for at least 14 weeks duration prior to screening, or adalimumab (greater than or equal to 40 mg SC every 2 weeks, or maximum tolerated dose) for at least 12 weeks prior to screening.
Key exclusion criteria (17 listed)
- Patients who have a form of arthritis or arthropathy, other than RA, or any current inflammatory condition that might confound the assessments (e.g., other connective tissue diseases or Lyme disease).
- Patients who have been enrolled in any investigational therapy study for the treatment of RA within 4 weeks prior to the start of the Treatment Period, or patients who are scheduled to receive investigational therapies or a plasma based apheresis procedure (e.g., a protein A column) for the treatment of RA during the course of the study.
- Patients unable to tolerate the extracorporeal volume shifts associated with ECP treatment due to the presence of any of the following conditions: uncompensated congestive heart failure, pulmonary edema, severe chronic obstructive pulmonary disease, severe asthma, renal failure, or hepatic failure.
- Patients with a poor tolerability of venipuncture or a lack of adequate venous access for required treatments and blood sampling.
- Note: Every attempt should be made to enroll patients who have adequate peripheral venous access.
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 |
|---|---|---|
| Methoxsalen | Drug | – |
| Extracorporeal Photopheresis | Procedure or surgery | – |
Primary outcome
ACR 20
Time frame: week 24 and week 28
At least a 20% improvement of ACR 20 from baseline
1 secondary outcome
ACR 50
Time frame: week 24 and week 28
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 Oct 2016.
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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.
EDWARD KEYSTONE, MD principal investigator
Rebecca MacDonald Centre for Arthritis
32 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Methoxsalen and Extracorporeal Photopheresis in people with Rheumatoid Arthritis, run by Mallinckrodt at 32 sites in 11 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 14 inclusion and 17 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 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, Germany, Italy, South Africa, Belgium and 6 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?
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?
ACR 20 (time frame: week 24 and week 28). 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 Oct 2016.