Phase IV Study, Betaseron Versus Copaxone for Relapsing Remitting or CIS Forms of MS Using Triple Dose Gad 3 T MRI (BECOME)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Stuart D Cook MD, University of Medicine and Dentistry New Jersey
ClinicalTrials.gov Identifier:
NCT00176592
First received: September 13, 2005
Last updated: September 25, 2013
Last verified: September 2013
  Purpose

This is the first comparison of efficacy of Betaseron and Copaxone for treatment of relapsing forms of MS.


Condition Intervention Phase
Multiple Sclerosis
Drug: Betaseron
Drug: Copaxone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase IV, Rater-blinded, Randomized Study, Comparing 250 mg of Betaseron With 20 mg of Copaxone in Patients With the Relapsing-remitting(RR) or CIS Forms of ms Using 3 Tesla(3T) Magnetic Resonance Imaging (MRI) With Triple-dose Gadolinium

Resource links provided by NLM:


Further study details as provided by Rutgers, The State University of New Jersey:

Primary Outcome Measures:
  • The primary outcome measure is the number of "combined active" lesions by monthly MRI at the conclusion of the study. [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The number of enhancing lesions. [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
  • The number of new lesions on long TR. [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
  • The number of "combined active" disease free patients. [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]

Enrollment: 93
Study Start Date: January 2003
Estimated Study Completion Date: January 2016
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Betaseron
Betaseron 250 micrograms SQ every other day
Drug: Betaseron
Betaseron 250 micrograms injected SQ every other day
Other Names:
  • Betaseron 250 mcg SQ every other day
  • Intaferon beta 1 b
Active Comparator: Copaxone
20 mg daily SQ
Drug: Copaxone
Copaxone 20 mg injected SQ every day (glatiramer acetate)
Other Name: Copaxone 20 mg injected SQ every day (glatiramer acetate)

Detailed Description:

We propose to perform a head to head comparison of Interferon beta and Copaxone for treatment of patients with CIS and RR forms of MS using acute changes on MRI as primary outcome. The study will be performed at the two clinical practice sites of the Multiple Sclerosis Center at University of Medicine and Dentistry New Jersey-New Jersey Medical School, One of the two FDA approved preparations of higher dose interferon beta (Betaseron) will be compared at standard dose every other day (QOD) 250 ug subcutaneously(SQ) with Copaxone at 20mg SQ daily (QD) in 70 to 80 patients. Although the current approved plan is to perform monthly MRIs for 1 year followed by another MRI at 2 years, the protocol has been changed to continue performing monthly MRIs during the second year of the study for all patients who complete their first year and up to January 31, 2006 when the study will end. The study uses brain imaging with 3 Tesla MRI with triple dose Gadolinium for primary and secondary outcomes and several clinical and cognitive measures for secondary outcomes. The sample size was estimated to detect a 40-50% difference in the number of active MS lesions by MRI between the two arms at 1 year follow up, consistent with the primary outcome measure. The primary outcome measure is the number of "combined-active" lesions by monthly MRI at the conclusion of the study, which includes contrast enhancing lesions and non-enhancing lesions on long Time repetition (TR) scans that have appeared since the most recent examination. Several secondary MRI outcome measures are studied in addition to the number of enhancing lesions and the number of new lesions on long TR images. We will examine the number of patients who remain "combined-active disease-free" for the duration of the study and the number of "combined-active disease-free" scans. Apart from these traditional methods of analysis by a reader who will be blinded to patient clinical status and therapy, objective volumetric analysis will be carried out. Making use of both automated and manual techniques, we will determine the overall burden of disease (the volume of lesions on long TR scans), the burden of active disease (the volume of brain enhancement) and the burden of chronic disease (the volume of lesions that are markedly hypointense on T1). Another MRI outcome measures will be detection of diffusion anisotropy differences, MR spectroscopy, and magnetization transfer ratio as summarized in Appendix 5. These new techniques have shown promise for detecting disease that cannot be detected with conventional MRI (13, 37).

In addition to MRI, several clinical and cognitive outcome measures will be used for secondary analysis. These include the number and severity of relapses measured by different methods, and change in disability measured by the Expanded Disability Status Scale (EDSS), the Neurological Rating Scale, and the Multiple Sclerosis Functional Composite (MSFC). The cognitive measures will be the subject's neurocognitive function measured by standard neurocognitive examination obtained by a licensed neuropsychologist and the Cognitive Stability Index (CSI), a novel Internet-based test of cognitive function in addition to the Paced Auditory Serial Addition Test (PASAT),which is a component of the MSFC.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

Patients must meet all of the following criteria at the time of the baseline visit in order to enter the trial:

  • Be Between 18 and 55 years of age, at baseline.
  • Be capable of informed consent in English prior to any study related procedures.Spanish speaking patients who do not read English well can give written informed consent if a relative or friend fluent in both English and Spanish has translated the consent and any questions the patient may have.
  • Be available and willing to complete all study assessments.
  • Presently meet one of the two following forms of multiple sclerosis:

    1. Relapsing-remitting ms plus evidence of recent disease activity as shown by the development of one or more clinical and/or MRI lesions during the 6 months prior to entry into the study.
    2. A CIS consistent with central nervous system (CNS) demyelination confirmed on ophthalmologic or neurological examination with onset within 6 months prior to study entry. Also:a- evidence of dissemination in space, there should be two or more brain MRI lesions ≥ 3 mm in size at least one of which should be ovoid and/or periventricular in location; and b- As evidence of dissemination in time, if the CIS is acute (≤1 month) there should be one or more non-enhancing lesion or if the CIS is not acute (older than 1 month) the MRI should show one or more enhancing lesions.

      • At baseline, have an EDSS between 0-5.5.
  • Females of childbearing potential must agree to practice adequate contraception methods. All females must have negative pregnancy test results at screening and a negative urine pregnancy test at baseline.
  • Screening laboratory results that confirm adequate bone marrow, renal, and hepatic function.

Exclusion criteria

Patients were not permitted into the study if they met any of the following criteria:

  • Onset of a relapse between screening and Study Day 1.
  • Present evidence or history of any conditions that could affect the CNS or interfere with the MRI results or any other evaluation in the study.
  • Possess any of the standard metallic devices or foreign bodies that are contraindications for MRI.
  • Patient weight and or size unable to fit in the 3T MRI scanner.
  • Pregnancy, as denoted by a positive serum pregnancy test at screening visit or a positive urine pregnancy test at the baseline visit. Subjects who are breast-feeding are also excluded.
  • Have a known allergy or hypersensitivity to Gadolinium-chelates, human proteins including albumin and interferons, or Glatiramer Acetate or Mannitol.
  • Uncontrolled, clinically significant heart diseases, such as dysrhythmias, angina, or uncompensated congestive heart failure. History of or current unstable medical conditions that could be deemed clinically significant.
  • Intolerance or any contraindication to acetaminophen, ibuprofen, or steroids.
  • Inability, in the opinion of the principal investigator or staff, to be compliant with protocol requirements for the duration of the study.
  • Participation in any clinical trial within the past six months
  • History or present evidence of addictions.
  • Have active peptic ulcer disease.
  • Inability to have subcutaneous injections administered.
  • Medical, psychiatric or other conditions that compromise the patient's ability to understand the study procedures.
  • Claustrophobia.
  • Uncontrolled head movements.
  • Treatment with any of the following in the indicated time frames: Any of the Interferons for > 6 months· Glatiramer acetate (Copaxone) for > 6 months.No prior use allowed of Total lymphoid irradiation, Anti-lymphocyte monoclonal antibody (e.g.(Campath-1H) .Mitoxantrone,cyclophosphamide, Azathioprine, intravenous immunoglobulin (IVIG), cyclosporine within 6 months before the screening visit·Any investigational drug 21 days before screening visit·Systemic corticosteroids·ACTH from screening visit through Study Day
  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: NCT00176592

Locations
United States, New Jersey
New Jersey Medical School
Newark, New Jersey, United States, 07103
Sponsors and Collaborators
University of Medicine and Dentistry of New Jersey
Investigators
Principal Investigator: Stuart D Cook, MD MD
  More Information

No publications provided

Responsible Party: Stuart D Cook MD, Director of multiples sclerosis treatment and diagnosis center, University of Medicine and Dentistry New Jersey
ClinicalTrials.gov Identifier: NCT00176592     History of Changes
Other Study ID Numbers: BECOME, 0120020167
Study First Received: September 13, 2005
Last Updated: September 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Rutgers, The State University of New Jersey:
Multiple Sclerosis
Brain
Betaseron
Copaxone
MRI

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

ClinicalTrials.gov processed this record on September 18, 2014