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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00221000




Registration number
NCT00221000
Ethics application status
Date submitted
13/09/2005
Date registered
22/09/2005
Date last updated
19/10/2016

Titles & IDs
Public title
Safety and Efficacy of Extracorporeal Photoimmune Therapy With UVADEX for the Treatment of Rheumatoid Arthritis
Scientific 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
Secondary ID [1] 0 0
RA-1
Universal Trial Number (UTN)
Trial acronym
RA-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Methoxsalen
Treatment: Surgery - Extracorporeal Photopheresis

Treatment: Drugs: Methoxsalen


Treatment: Surgery: Extracorporeal Photopheresis
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
ACR 20
Timepoint [1] 0 0
week 24 and week 28
Secondary outcome [1] 0 0
ACR 50
Timepoint [1] 0 0
week 24 and week 28

Eligibility
Key inclusion criteria
- 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.

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).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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).

- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2003
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/11/2006
Sample size
Target
Accrual to date
Final
86
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Brisbane Hospital - Herston
Recruitment postcode(s) [1] 0 0
- Herston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Maryland
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
New Jersey
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Rhode Island
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
Austria
State/province [10] 0 0
Vienna
Country [11] 0 0
Belgium
State/province [11] 0 0
Bruxelles
Country [12] 0 0
Belgium
State/province [12] 0 0
Diepenbeek
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
France
State/province [14] 0 0
Lille
Country [15] 0 0
France
State/province [15] 0 0
Lyon
Country [16] 0 0
Germany
State/province [16] 0 0
Bad Bruckenau
Country [17] 0 0
Germany
State/province [17] 0 0
Berlin
Country [18] 0 0
Germany
State/province [18] 0 0
Erlangen
Country [19] 0 0
Germany
State/province [19] 0 0
Hamburg
Country [20] 0 0
Germany
State/province [20] 0 0
Koln
Country [21] 0 0
Germany
State/province [21] 0 0
Munster
Country [22] 0 0
Germany
State/province [22] 0 0
Oldenburg
Country [23] 0 0
Italy
State/province [23] 0 0
Firenze
Country [24] 0 0
Italy
State/province [24] 0 0
Genova
Country [25] 0 0
Italy
State/province [25] 0 0
Siena
Country [26] 0 0
Mexico
State/province [26] 0 0
Jalisco
Country [27] 0 0
Slovakia
State/province [27] 0 0
Bratislava
Country [28] 0 0
South Africa
State/province [28] 0 0
Bloemfontein
Country [29] 0 0
South Africa
State/province [29] 0 0
Cape Town

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Mallinckrodt
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.

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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00221000
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
EDWARD KEYSTONE, MD
Address 0 0
Rebecca MacDonald Centre for Arthritis
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00221000