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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02296346
Recruitment Status : Terminated (Low enrollment/PI relocated. New site couldn't reach agreement with manufacturer)
First Posted : November 20, 2014
Results First Posted : August 14, 2019
Last Update Posted : August 14, 2019
Sponsor:
Collaborator:
Mallinckrodt
Information provided by (Responsible Party):
Daniel Couriel, University of Utah

Tracking Information
First Submitted Date  ICMJE November 18, 2014
First Posted Date  ICMJE November 20, 2014
Results First Submitted Date  ICMJE May 20, 2019
Results First Posted Date  ICMJE August 14, 2019
Last Update Posted Date August 14, 2019
Actual Study Start Date  ICMJE October 2014
Actual Primary Completion Date June 13, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 8, 2019)
Multiple Sclerosis Functional Composite (MSFC) Z-score and Expanded Disability Status Scale (EDSS) [ Time Frame: 1 year ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 19, 2014)
To evaluate the effect of ECP compared to IVMP on accumulation of disability (composite of components of MSFC score) at 1 year (52 weeks) in individuals with secondary progressive multiple sclerosis (SPMS [ Time Frame: 1 year ]
To evaluate the effect of ECP compared to IVMP on accumulation of disability at 1 year (52 weeks) in individuals with secondary progressive multiple sclerosis (SPMS). Disability will be assessed using a composite measure that takes into account changes in the EDSS and components of the MSFC score.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 8, 2019)
Immunological Parameters in Relation to SPMS [ Time Frame: 2 year ]
Changes in immunological parameters that occur following initiation of ECP or corticosteroids and any relevant correlation with clinical outcomes
Original Secondary Outcome Measures  ICMJE
 (submitted: November 19, 2014)
Immunological parameters in relation to SPMS [ Time Frame: 2 year ]
• To determine whether changes in immunological parameters that occur following initiation of ECP or corticosteroids correlate with clinical outcomes
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Open-Label Study to Evaluate the Efficacy of ECP in Secondary Progressive Multiple Sclerosis
Official Title  ICMJE 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)
Brief Summary 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

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Secondary Progressive Multiple Sclerosis
Intervention  ICMJE
  • Drug: SoluMedrol
    Infusion of drug subcutaneously, once a month.
    Other Name: Corticosteroids
  • Device: Extracorporeal Photopheresis
    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.
    Other Names:
    • ECP
    • Cellex machine
    • Therakos
Study Arms  ICMJE
  • Active Comparator: Corticosteroid arm
    Patients will receive 1 gram of IV SoluMedrol over 1 hour, once every month for 12 months.
    Intervention: Drug: SoluMedrol
  • Experimental: Extracorporeal Photopheresis

    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

    Intervention: Device: Extracorporeal Photopheresis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 8, 2019)
13
Original Estimated Enrollment  ICMJE
 (submitted: November 19, 2014)
66
Actual Study Completion Date  ICMJE May 10, 2018
Actual Primary Completion Date June 13, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02296346
Other Study ID Numbers  ICMJE HUM00083301
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Daniel Couriel, University of Utah
Study Sponsor  ICMJE University of Utah
Collaborators  ICMJE Mallinckrodt
Investigators  ICMJE
Principal Investigator: Benjamin Segal, MD University of Michigan, Director of Multiple Sclerosis Center
Principal Investigator: Daniel Couriel, MD University of Utah, Huntsman Cancer Institute, Internal Medicine
PRS Account University of Utah
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP