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

NCT02296346 | Terminated Results DMC

• 1 other identifier: HUM00083301
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Secondary Progressive Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Immunological Parameters in Relation to SPMS

  2 year

Study Arms (2)

Corticosteroid arm

ACTIVE COMPARATOR

Patients will receive 1 gram of IV SoluMedrol over 1 hour, once every month for 12 months.

Drug: SoluMedrol

Extracorporeal Photopheresis

EXPERIMENTAL

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

Interventions

SoluMedrol DRUG

Infusion of drug subcutaneously, once a month.

Also known as: Corticosteroids

Corticosteroid arm

Extracorporeal Photopheresis DEVICE

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.

Also known as: ECP, Cellex machine, Therakos

Extracorporeal Photopheresis

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• University of Utah: lead
• Mallinckrodt: collaborator

Study Sites (1)

University of Michigan Health Systems

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Interventions

Methylprednisolone Hemisuccinate; Adrenal Cortex Hormones; Photopheresis

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Methylprednisolone; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; PUVA Therapy; Ultraviolet Therapy; Phototherapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative

Limitations and Caveats

Analysis of the data in this study was severely limited by the high dropout rate and low enrollment numbers. Given that only 2/13 participants completed the study, we do not have enough outcome data to complete a meaningful analysis.

Results Point of Contact

• Title: Dr. Daniel Couriel
• Organization: Huntsman Cancer Institute, University of Utah

dan.couriel@hci.utah.edu

801-213-3082

Study Officials

• Benjamin Segal, MD

  University of Michigan, Director of Multiple Sclerosis Center

  PRINCIPAL INVESTIGATOR

• Daniel Couriel, MD

  University of Utah, Huntsman Cancer Institute, Internal Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: November 18, 2014
• First Posted: November 20, 2014
• Study Start: October 1, 2014
• Primary Completion: June 13, 2017
• Study Completion: May 10, 2018
• Last Updated: August 14, 2019
• Results First Posted: August 14, 2019

Record last verified: 2019-08

Locations

US (1)