Glatiramer Acetate for Multiple Sclerosis With Autoimmune Comorbidities

This study has been completed.
Sponsor:
Collaborator:
Teva Pharmaceuticals USA
Information provided by (Responsible Party):
University of Southern California
ClinicalTrials.gov Identifier:
NCT01456416
First received: August 19, 2011
Last updated: April 2, 2013
Last verified: April 2013
  Purpose

The incidence of autoimmune conditions is at least 2-3 times higher in Multiple Sclerosis population than in general population. These MS patients category response unfavorably to the Interferon. The investigators suggest that autoimmune co morbidity can serve as a biological marker predicting good response to GA.


Condition Phase
Relapsing Remitting Multiple Sclerosis
Phase 4

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pilot Study for Evaluation of Glatiramer Acetate in RRMS Patients With Comorbid Autoimmune Conditions

Resource links provided by NLM:


Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • Change from Baseline in Clinical Global Impression Scale (CGI-1). [ Time Frame: Comparison of CGI-1 score pre- and post-treatment.at 6 months. ] [ Designated as safety issue: Yes ]
    The primary objective is to determine whether daily GA injections do not aggravate comorbid autoimmune conditions.


Secondary Outcome Measures:
  • Secondary objectives include Visual Analog Scale (VAS). [ Time Frame: Secondary objective will be done at Baseline, Mo 3, Mo 6. ] [ Designated as safety issue: Yes ]
    Comparison of VAS data pre- and post-treatment (Baseline, Mo 3, Mo 6).

  • Secondary objectives include Expanded Disability Status Scale (EDSS) [ Time Frame: Secondary objective will be done at Baseline, Mo 3, Mo 6. ] [ Designated as safety issue: Yes ]
    Comparison of EDSS score pre- and post-treatment (Baseline, Mo 3, Mo 6).

  • Secondary objectives include concomitant medication review. [ Time Frame: Secondary objective will be done at Baseline, Mo 3, Mo 6. ] [ Designated as safety issue: Yes ]
    Comparison/review of Concomitant Medications used for co-morbid condition treatment (Baseline, Mo 3, Mo 6).


Enrollment: 10
Study Start Date: September 2011
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
Glatiramer Acetate
GA administered SQ daily in MS patients who met all Inclusion-Exclusion Criteria and were approved by their Health Care Plans for GA treatment.

Detailed Description:

Multiple Sclerosis (MS) is an auto-immune neurodegenerative disease that affects more than 400,000 individuals in the United States, and 2.5 million worldwide (www.nationalmssociety.org). The main pathogenic mechanism in MS involves an inflammatory condition that damages the myelin of the central nervous system (CNS), resulting in axonal damage and neurological impairment, often leading to severe disability. MS is one of the most common causes of neurological disability in young and middle-aged adult individuals, and as such has a tremendous physical, psychological and social impact on patients' lives. MS is a complex disease diagnosed by McDonald criteria with different clinical and pathological phenotypes. Several forms of MS have been described: Relapsing-Remitting (RRMS), Secondary-Progressive MS (SPMS), Progressive-Relapsing MS (PRMS), and Primary-Progressive MS (PPMS).

Glatiramer Acetate (GA) and Beta-Interferons (β-IFNs) are well established first-line immunomodulating treatment options for relapsing remitting multiple sclerosis (RRMS) with excellent safety profiles. The mechanisms of action of GA and IFNs are different. It is well known that in general Disease-Modifying Treatments (DMTs) reduce relapse rate in more than half of the multiple sclerosis (MS) patients who receive DMT, while having little if any effect on the rest. It has been speculated that the response to beta-interferons or GA may have genetic basis. As Axtell RC et al. indicated the experimental autoimmune encephalomyeilits (EAE) in mouse caused by TH1 cells generally respond well to interferon-beta, while EAE caused by TH17 cells get worse with interferon-beta.

Autoimmune disease is an extreme situation where the autoimmune response overshoots and goes out of control. The other extreme is a degenerative disorder, where the autoimmune response is not strong enough for effective protection, and degeneration therefore continues. GA being an immunomodulator may provide both properly regulated immune suppression (in the case of autoimmune disease) and properly regulated immune activation (in the case of the neurodegenerative disease).

Autoimmune conditions cluster in families with high risk for multiple sclerosis than in general population which suggests that the disease might arise on a background of a generalized susceptibility to autoimmunity. Occurrence of psoriasis, autoimmune thyroiditis, vasculitis, rheumatoid arthritis, scleroderma, lupus are seen more commonly in MS patients. Many of these patients initially get started on beta-IFNs, and usually do not do well on them. According to Investigator's and the USC MS Comprehensive Care Center experience, autoimmune co-morbidity associated with MS can serve as a biological marker predicting good response to GA and unfavorable response to the IFNs.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

All Subjects meeting inclusion/exclusion criteria.

Criteria

Inclusion Criteria:

  • Clinically definite multiple sclerosis defined by McDonald Criteria.
  • Between 18-60 years of age.
  • Subject must able to understand and sign the IRB- approved informed consent form prior to the performance of any study-specific procedures and is willing to comply with the required scheduling and assessments of the protocol.
  • Subjects who are women of childbearing potential, must have a negative serum pregnancy test at the screening visit, and must be willing to practice a reliable birth-control method.
  • Subjects must have officially diagnosed and documented co-morbid, other than MS, autoimmune condition (psoriasis, vasculitis, thyroiditis or rheumatoid arthritis).
  • At the time of enrollment patients were on beta IFN (Avonex, Betaseron or Rebif) treatment for at least 3 months.

Exclusion Criteria:

  • Women who are either pregnant or breastfeeding, and women of child-bearing potential (defined as not surgically sterile or at least two years postmenopausal) who are not using one of the following birth control methods: tubal ligation, implantable contraception device, oral, patch, injectable or transdermal contraceptive, barrier method or sexual activity restricted to vasectomized partner.
  • Any clinically significant general health conditions that may interfere with the trial participation.
  • Subject has a history of drug or alcohol abuse within the past year.
  • Subject had corticosteroid treatment within last 90 days.
  • Subject started new medication within last 30 days.
  • Subject is a participant in another research project.
  • Subject has contraindications for GA treatment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01456416

Locations
United States, California
USC MS Comprehensive Care Center & Research Group
Los Angeles, California, United States, 90033
Sponsors and Collaborators
University of Southern California
Teva Pharmaceuticals USA
Investigators
Principal Investigator: Regina Berkovich, M.D.Ph.D LAC+USC
  More Information

No publications provided

Responsible Party: University of Southern California
ClinicalTrials.gov Identifier: NCT01456416     History of Changes
Other Study ID Numbers: GAforMS with AutoimmuneComor
Study First Received: August 19, 2011
Last Updated: April 2, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Southern California:
RRMS
Multiple Sclerosis
Glatiramer Acetate
Autoimmune Comorbidities
Psoriasis
Autoimmune Thyroiditis
Vasculitis
Rheumatoid Arthritis

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Copolymer 1
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents

ClinicalTrials.gov processed this record on October 01, 2014