RA-1: Safety and Efficacy of Extracorporeal Photoimmune Therapy With UVADEX for the Treatment of Rheumatoid Arthritis

• Sponsor: Mallinckrodt (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00221000
• Collaborator: (none)
• Enrollment: 86
• Locations: 32
• Duration (Months): 39
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Methoxsalen; Procedure: Extracorporeal Photopheresis	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 86 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: Aug 1, 2003
• Actual Primary Completion Date: Oct 1, 2006
• Actual Study Completion Date: Nov 1, 2006

Outcome Measures

Primary Outcome Measures

1. ACR 20 [week 24 and week 28]

   At least a 20% improvement of ACR 20 from baseline

Secondary Outcome Measures

1. ACR 50 [week 24 and week 28]

   Improvement of at least 50% from baseline on ACR 50

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Carroll County Arthritis and Osteoporosis Center	Westminister	Maryland	United States
2	Clinical Pharmacology Study Group	Worchester	Massachusetts	United States
3	Morristown Memorial Hospital	Morristown	New Jersey	United States
4	AAIR Research Center	Rochester	New York	United States
5	Carolina Arthritis Associates	Wilmington	North Carolina	United States
6	Rheumatic Disease Associates	Willow Grove	Pennsylvania	United States
7	Rheumatology Associates	Providence	Rhode Island	United States
8	UT Southwestern Medical Center	Dallas	Texas	United States
9	Arthritis and Osteoporosis Center of South Texas	San Antonio	Texas	United States
10	Benaroya Research Institute at Virginia Mason	Seattle	Washington	United States
11	Royal Brisbane Hospital	Herston		Australia
12	General Hospital of Vienna	Vienna		Austria
13	Hospital Brugmann	Bruxelles		Belgium
14	Limburgs Universitair Centrum	Diepenbeek		Belgium
15	Rebecca MacDonald Centre for Arthritis	Toronto	Ontario	Canada
16	CHRU de Lille	Lille		France
17	Hopital Edouard Herriot	Lyon		France
18	Franz von Prummer Klinik	Bad Bruckenau		Germany
19	University of Charite Clinic for Rheumatology and Immunology	Berlin		Germany
20	Medizinische Klinik III	Erlangen		Germany
21	Abt. Rheumatologie und Klinische Immunologie	Hamburg		Germany
22	Klinikum der Universitat zu Koln	Koln		Germany
23	Westfalische wilhelms-universitat Munster	Munster		Germany
24	Medizinische Klinik des Evangelischen Kranken	Oldenburg		Germany
25	Universita degli Studi di Firenze	Firenze		Italy
26	Universita de Genova - Ospedale S. Martino	Genova		Italy
27	University of Siena-Italy	Siena		Italy
28	OPD- Hospital Civil "Dr. Jaun I. Menchaca"	Guadalajara	Jalisco	Mexico
29	Reumatologicka ambulancia, Polinika	Bratislava		Slovakia
30	South African National Blood Service	Bloemfontein		South Africa
31	Christian Barnard Mermorial Hospital	Cape Town		South Africa
32	D6 Rheumatology Clinic and E5 Hematology Unit	Cape Town		South Africa

Sponsors and Collaborators

• Mallinckrodt

Investigators

• Principal Investigator: EDWARD KEYSTONE, MD, Rebecca MacDonald Centre for Arthritis

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mallinckrodt
• ClinicalTrials.gov Identifier: NCT00221000
• Other Study ID Numbers: RA-1
• First Posted: Sep 22, 2005
• Last Update Posted: Oct 19, 2016
• Last Verified: Oct 1, 2016

• Keywords provided by Mallinckrodt: Rheumatoid Arthritis
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Methoxsalen

Study Results

No Results Posted as of Oct 19, 2016