Clinical trial NCT00221000: Safety and Efficacy of Extracorporeal Photoimmune Therapy With UVADEX for the Treatment of Rheumatoid Arthritis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Lead sponsor: Mallinckrodt
Sponsor class: INDUSTRY
First posted: 2005-09-22
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

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.

Primary outcomes:
measure: ACR 20
timeFrame: week 24 and week 28
Secondary outcomes:
measure: ACR 50
timeFrame: week 24 and week 28
Other outcomes:
Locations:
city: Westminister
country: United States
facility: Carroll County Arthritis and Osteoporosis Center
state: Maryland
city: Worchester
country: United States
facility: Clinical Pharmacology Study Group
state: Massachusetts
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: Rochester
country: United States
facility: AAIR Research Center
state: New York
city: Wilmington
country: United States
facility: Carolina Arthritis Associates
state: North Carolina
city: Willow Grove
country: United States
facility: Rheumatic Disease Associates
state: Pennsylvania
city: Providence
country: United States
facility: Rheumatology Associates
state: Rhode Island
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: San Antonio
country: United States
facility: Arthritis and Osteoporosis Center of South Texas
state: Texas
city: Seattle
country: United States
facility: Benaroya Research Institute at Virginia Mason
state: Washington
city: Herston
country: Australia
facility: Royal Brisbane Hospital
city: Vienna
country: Austria
facility: General Hospital of Vienna
city: Bruxelles
country: Belgium
facility: Hospital Brugmann
city: Diepenbeek
country: Belgium
facility: Limburgs Universitair Centrum
city: Toronto
country: Canada
facility: Rebecca MacDonald Centre for Arthritis
state: Ontario
city: Lille
country: France
facility: CHRU de Lille
city: Lyon
country: France
facility: Hopital Edouard Herriot
city: Bad Bruckenau
country: Germany
facility: Franz von Prummer Klinik
city: Berlin
country: Germany
facility: University of Charite Clinic for Rheumatology and Immunology
city: Erlangen
country: Germany
facility: Medizinische Klinik III
city: Hamburg
country: Germany
facility: Abt. Rheumatologie und Klinische Immunologie
city: Koln
country: Germany
facility: Klinikum der Universitat zu Koln
city: Munster
country: Germany
facility: Westfalische wilhelms-universitat Munster
city: Oldenburg
country: Germany
facility: Medizinische Klinik des Evangelischen Kranken
city: Firenze
country: Italy
facility: Universita degli Studi di Firenze
city: Genova
country: Italy
facility: Universita de Genova - Ospedale S. Martino
city: Siena
country: Italy
facility: University of Siena-Italy
city: Guadalajara
country: Mexico
facility: OPD- Hospital Civil "Dr. Jaun I. Menchaca"
state: Jalisco
city: Bratislava
country: Slovakia
facility: Reumatologicka ambulancia, Polinika
city: Bloemfontein
country: South Africa
facility: South African National Blood Service
city: Cape Town
country: South Africa
facility: Christian Barnard Mermorial Hospital
city: Cape Town
country: South Africa
facility: D6 Rheumatology Clinic and E5 Hematology Unit
Study officials:
affiliation: Rebecca MacDonald Centre for Arthritis
name: EDWARD KEYSTONE, MD
role: PRINCIPAL_INVESTIGATOR
References: