Open-Label Study to Evaluate the Efficacy of ECP in Secondary Progressive Multiple Sclerosis

Study Overview
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Brief Summary
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In this research study, the investigators will determine whether a procedure called Extracorporeal Photopheresis (ECP) is helpful in preventing progression of disability in people with SPMS when compared to monthly corticosteroid infusions. This study will determine whether ECP has an effect on inflammatory cells in people with SPMS and whether it has a beneficial therapeutic effect.

Detailed Description
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This is a Phase II randomized, open-label study to evaluate the efficacy of extracorporeal photopheresis (ECP) versus IVMP on disability progression in subjects with SPMS. At the initial screening visit, an extensive medical history will be obtained and a detailed neurological examination will be performed to determine eligibility. Subjects who meet eligibility criteria will be enrolled in one of two study arms. Subjects will be randomized at a 1:1 ratio to receive ECP (study arm) or active treatment with intravenous methylprednisolone pulses (control arm) administered every 4 Weeks (1 gram per infusion) for 52 weeks. ECP will be administered according to the following schedule: Study Arm: Weeks 1-8: 3 times per week Weeks 9-16: Twice per week Weeks 17-36: Treatment on two consecutive days every 2 weeks (or optionally, one treatment per week) Weeks 37-43: Once every 2 weeks Weeks 44-52: Once every 4 Weeks All subjects, including patients who receive corticosteroids, will be evaluated using the MSFC tool at baseline and every 3 months through 2 years. They will also be scored using the EDSS at baseline and every 3 months through 2 years. Subjects in the control arm will be evaluated by MSFC and EDSS during the week prior to their next intravenous methylprednisolone infusion and every three months from baseline through two year mark. Blood will be collected for immune function (cytokines) testing at baseline, and months 3, 6, 9 and 12. MRI will be done at baseline as well as months 6 and 12 following initiation of treatment; if the disability measurements are stable or improved at any point in time, then ECP will be continued per protocol.. Patients in the ECP arm should have all of their treatments with the CELLEX ® System. Patients randomized to the ECP arm must receive their treatment within 5 days of baseline visit. In the ECP process, UVADEX ® (methoxsalen) Sterile Solution will be injected directly the recirculation bag of the extracorporeal circuit after completion of the buffy coat collection. The dose of UVADEX® (methoxsalen) Sterile Solution will be calculated based on the standard treatment volume formula.

Official Title
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A Randomized, Controlled, Open-Label Study to Evaluate the Efficacy of Extracorporeal Photopheresis (ECP) Versus Corticosteroids in the Treatment of Patients With Secondary Progressive Multiple Sclerosis (SPMS)

Conditions
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Secondary Progressive Multiple Sclerosis

Intervention / Treatment
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* Drug: SoluMedrol
* Device: Extracorporeal Photopheresis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with SPMS based on the Recommended Diagnostic Criteria for MS and clinical course. Demonstrate EDSS scores between 3 to 6.5 at screening. Documented EDSS progression in the 2 years prior to screening of 1 point or greater for patients with an EDSS score less than 6 at baseline, and greater than or equal to 0.5 Documented absence of clinical relapse within 2 years of screening Age ≥ 18 ≤ 75 years Weight > 40≤ 150 kg. Absolute Neutrophil count ≥ 2,000 per μL Hematocrit ≥ 28 % and platelet count > 100,000 per μL (with or without transfusion support) Willingness to use at least 1 reliable method of birth control (e.g. abstinence, oral contraceptives, intrauterine devices, barrier method with spermicide, or surgical sterilization) throughout the study for all men and women of childbearing potential Willingness to participate in all study visits and procedures, as outlined in the informed consent Patients able to give informed consent. Patients must have adequate peripheral venous access to initiate ECP therapy. Exclusion Criteria: Absolute medical contraindication to corticosteroid treatment Absolute medical contraindication to receive ECP Clinical relapse within 2 years of screening Laboratory evidence of any of the following: WBC < 2,000 cells per uL Serum transaminase levels > x 2 UNL HgbA1C > 6% Concurrent diagnosis of a neurological condition or autoimmune disease other than MS Evidence of known infection with human immunodeficiency virus (HIV) or active (not including latent) Hepatitis B (laboratory testing is not required if virus status is already known) Uncontrolled infection requiring treatment at study entry Hypersensitivity or allergy to psoralen (methoxsalen) Hypersensitivity or allergy to both heparin and citrate products (If hypersensitive or allergic to only one of these products, exclusion does not apply) Inability to tolerate fluid changes associated with ECP (e.g. inadequate renal, hepatic, pulmonary and cardiac function leading to enable patient to tolerate extracorporeal volume shifts associated with ECP) Presence of aphakia or photosensitive disease (systemic lupus erythematosis, porphyrias, albinism, etc.) Women who are pregnant and/or lactating. Use of any investigational drug/treatment at the time of enrollment or within the previous 60 days, or five elimination half-lives, or until the expected pharmacodynamic effect has returned to baseline, whichever is longer. Initiation of dalfampridine or change in the dose of dalfampridine within 6 months prior to randomization Treatment with any of the medications or procedures listed below: Glatiramer acetate, interferon-beta, fingolimod, teriflunomide or dimethylfumarate within 3 months prior to randomization Natalizumab within 6 months prior to randomization Cyclophosphamide within 1year prior to randomization Mitoxantrone within 2 years prior to randomization Rituximab, ofatumumab, ocrelizumab, cladribine, daclizumab within 2 years prior Intravenous immunoglobulin within 6 months prior to randomization Plasmapheresis within 1 year prior to randomization Corticosteroids within 3 months prior to screening Inability to undergo MRI scans Contraindication to gadolinium due to past allergic, hypersensitive or adverse reaction or impaired renal function Any other disease or condition which, in the opinion of the investigator, could interfere with participation in the study according to the study protocol, or with the ability of the patients to cooperate and comply with study procedures. Poor venous access Previous history of skin cancer, leukemia/lymphoma/myeloma or bone marrow transplant. History of cataracts Patients taking Coumadin who are unable to switch from oral anticoagulants to enoxaparin.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Corticosteroid arm<br>Patients will receive 1 gram of IV SoluMedrol over 1 hour, once every month for 12 months. | Drug: SoluMedrol<br>* Infusion of drug subcutaneously, once a month.<br>* Other names: Corticosteroids;|
| Experimental: Extracorporeal Photopheresis<br>Patient will receive an Extracorporeal Photopheresis treatment at a set frequency over the course of 1 year. The treatment takes about 2-3 hours per session to complete. The treatment schedule is as follows: ECP will be administered according to the following schedule: Study Arm: Weeks 1-8: 3 times per week Weeks 9-16: Twice per week Weeks 17-36: Treatment on two consecutive days every 2 weeks (or optionally, one treatment per week) Weeks 37-43: Once every 2 weeks Weeks 44-52: Once every 4 Weeks | Device: Extracorporeal Photopheresis<br>* This intervention is the placement of up to two IV's to extract your blood as a set volume, separate out the white cells and return the red cells to your body. Then the white cells are treated with a drug called UVADEX (methoxsalen), excited by a UV light and returned to your body. Once IV is to withdraw your blood and the other is to return your blood to your body.<br>* Other names: Therakos;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiple Sclerosis Functional Composite (MSFC) Z-score and Expanded Disability Status Scale (EDSS) | MSFC score is a composite score calculated from 3 tests: 1) Timed 25-Foot walk (leg function); 2) 9-Hole Peg Test (arm function); and 3) Paced Auditory Serial Addition Test (cognitive function). The results are combined to create a single score (the MSFC Z-Score) to measure performance and change over time in subjects with MS. MSFC Z-score = {Z arm + Z leg + Z cognitive} / 3.0. A positive score indicates that, on average, an individual performed better than the reference population and a negative score indicates that, on average, an individual performed worse than the reference population. The Expanded Disability Status Scale (EDSS) is used to quantify disability due to symptoms of MS and to track changes in disability status over time. Scores range from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). Scores are determined by performing a neurological exam and given in increments of 0.5. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunological Parameters in Relation to SPMS | Changes in immunological parameters that occur following initiation of ECP or corticosteroids and any relevant correlation with clinical outcomes | 2 year |