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

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

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

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Betaseron; Drug: Copaxone

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.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • New Jersey Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Betaseron; Betaseron 250 micrograms SQ every other day and Triple-Dose Gadolinium at each MRI	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; Copaxone 20 mg daily SQ and Triple-Dose Gadolinium at each MRI	Drug: Copaxone; Copaxone 20 mg injected SQ every day (glatiramer acetate); Other Names: Copaxone 20 mg injected SQ every day (glatiramer acetate)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Primary Outcome Measure is the Number of "Combined Active Lesions" (CAL) by Monthly MRI at the Conclusion of the Study.	Results are per patient mean number of lesions per scan. Results are per patient mean number of lesions per elapsed month. Contrasts types are: IFN 1b interferon beta 1b and GA glatiramer acetate.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Enhancing Lesions.	The first part of the secondary outcome measure is the total number of enhancing lesions per patient per treatment arm. The second part of the secondary outcome is the total number of new enhancing lesions per patient per treatment arm.	up to 2 years
The Number of MRI Disease Free Patients.	The 1 year MRI results were used to determine the quantity of disease free patients per contrast type.	1 year

Collaborators and Investigators

• Sponsor: University of Medicine and Dentistry of New Jersey
• Investigators: Principal Investigator: Stuart D Cook, MD, MD

Publications and helpful links

General Publications

• Cadavid D, Wolansky LJ, Skurnick J, Lincoln J, Cheriyan J, Szczepanowski K, Kamin SS, Pachner AR, Halper J, Cook SD. Efficacy of treatment of MS with IFNbeta-1b or glatiramer acetate by monthly brain MRI in the BECOME study. Neurology. 2009 Jun 9;72(23):1976-83. doi: 10.1212/01.wnl.0000345970.73354.17. Epub 2009 Mar 11.
• Cadavid D, Cheriyan J, Skurnick J, Lincoln JA, Wolansky LJ, Cook SD. New acute and chronic black holes in patients with multiple sclerosis randomised to interferon beta-1b or glatiramer acetate. J Neurol Neurosurg Psychiatry. 2009 Dec;80(12):1337-43. doi: 10.1136/jnnp.2008.171090. Epub 2009 Aug 16.
• Maranzano J, Rudko DA, Nakamura K, Cook S, Cadavid D, Wolansky L, Arnold DL, Narayanan S. MRI evidence of acute inflammation in leukocortical lesions of patients with early multiple sclerosis. Neurology. 2017 Aug 15;89(7):714-721. doi: 10.1212/WNL.0000000000004227. Epub 2017 Jul 19.

Study record dates

Study Major Dates

• Study Start: January 1, 2003
• Primary Completion (Actual): January 1, 2007
• Study Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 15, 2005

Study Record Updates

• Last Update Posted (Actual): November 16, 2021
• Last Update Submitted That Met QC Criteria: October 18, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: MRI; Multiple Sclerosis; Brain; Copaxone; Betaseron
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Adjuvants, Immunologic; Interferon beta-1b; Glatiramer Acetate; (T,G)-A-L
• Other Study ID Numbers: 0120020167 (Other Identifier: Rutgers)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No