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

• Sponsor: University of Medicine and Dentistry of New Jersey (Other)
• Overall Status: Completed
• CT.gov ID: NCT00176592
• Collaborator: (none)
• Enrollment: 75
• Location: 1
• Arms: 2
• Duration (Months): 48
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Betaseron; Drug: Copaxone	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (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
• Study Start Date: Jan 1, 2003
• Actual Primary Completion Date: Jan 1, 2007
• Actual Study Completion Date: Jan 1, 2007

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

1. The Primary Outcome Measure is the Number of "Combined Active Lesions" (CAL) by Monthly MRI at the Conclusion of the Study. [up to 2 years]

   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.

Secondary Outcome Measures

1. The Number of Enhancing Lesions. [up to 2 years]

   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.

2. The Number of MRI Disease Free Patients. [1 year]

   The 1 year MRI results were used to determine the quantity of disease free patients per contrast type.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Suhayl Dhib-Jalbut, MD, Professor and Chair, Department of Neurology, NJMS & RWJMS, Rutgers, The State University of New Jersey
• ClinicalTrials.gov Identifier: NCT00176592
• Other Study ID Numbers: 0120020167; 0120020167
• First Posted: Sep 15, 2005
• Last Update Posted: Nov 16, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Suhayl Dhib-Jalbut, MD, Professor and Chair, Department of Neurology, NJMS & RWJMS, Rutgers, The State University of New Jersey: Multiple Sclerosis; Brain; Betaseron; Copaxone; MRI
• Additional relevant MeSH terms: Multiple Sclerosis; Sclerosis; Glatiramer Acetate; Interferon beta-1b; (T,G)-A-L

Study Results

Participant Flow

Arm/Group Title	Betaseron	Copaxone
Arm/Group Description	Betaseron 250 micrograms SQ every other day Betaseron: Betaseron 250 micrograms injected SQ every other day	20 mg daily SQ Copaxone: Copaxone 20 mg injected SQ every day (glatiramer acetate)
Period Title: Overall Study
STARTED	36	39
Followed for 1 Year	35	35
Followed for 2 Years	29	35
COMPLETED	36	39
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Betaseron	Copaxone	Total
Arm/Group Description	Betaseron 250 micrograms SQ every other day Betaseron: Betaseron 250 micrograms injected SQ every other day	20 mg daily SQ Copaxone: Copaxone 20 mg injected SQ every day (glatiramer acetate)	Total of all reporting groups
Overall Participants	36	39	75
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	36 100%	39 100%	75 100%
>=65 years	0 0%	0 0%	0 0%
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	36	36	36
Sex: Female, Male (Count of Participants)
Female	27 75%	25 64.1%	52 69.3%
Male	9 25%	14 35.9%	23 30.7%
Region of Enrollment (participants) [Number]
United States	36 100%	39 100%	75 100%

Outcome Measures

1. Primary Outcome

Title	The Primary Outcome Measure is the Number of "Combined Active Lesions" (CAL) by Monthly MRI at the Conclusion of the Study.
Description	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.
Time Frame	up to 2 years

Outcome Measure Data

Analysis Population Description

Randomization was stratified by the presence or absence of enhancement. Analysis was intention to treat.

Arm/Group Title	Betaseron	Copaxone
Arm/Group Description	Betaseron 250 micrograms SQ every other day Betaseron: Betaseron 250 micrograms injected SQ every other day	20 mg daily SQ Copaxone: Copaxone 20 mg injected SQ every day (glatiramer acetate)
Measure Participants	36	39
Measure Combined Active Lesions	1688	1053
Mean (Standard Deviation) [Average number of lesions per scan]	0.63 (2.76)	0.58 (2.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Betaseron, Copaxone
	Comments	This includes p value for rank sum test treatment comparison. This includes p value for rank sum test treatment comparison of intention to treat study population.
	Type of Statistical Test	Superiority
	Comments	This includes p value for rank sum test treatment comparison. This includes p value for rank sum test treatment comparison of intention to treat study population.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.05
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	The Number of Enhancing Lesions.
Description	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.
Time Frame	up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Betaseron	Copaxone
Arm/Group Description	Betaseron 250 micrograms SQ every other day Betaseron: Betaseron 250 micrograms injected SQ every other day	20 mg daily SQ Copaxone: Copaxone 20 mg injected SQ every day (glatiramer acetate)
Measure Participants	31	30
Measure Enhancing Lesion	1531	973
Number [New Enhancing Lesion]	878	626

3. Secondary Outcome

Title	The Number of MRI Disease Free Patients.
Description	The 1 year MRI results were used to determine the quantity of disease free patients per contrast type.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Betaseron	Copaxone
Arm/Group Description	Betaseron 250 micrograms SQ every other day Betaseron: Betaseron 250 micrograms injected SQ every other day	20 mg daily SQ Copaxone: Copaxone 20 mg injected SQ every day (glatiramer acetate)
Measure Participants	36	39
The number of relapse-free patients at the completion of the study.	19 52.8%	28 71.8%
Free of combined active lesions, namely the combination of enhancing lesions plus new T2 lesions.	7 19.4%	10 25.6%

Adverse Events

Time Frame	Adverse events in the form of symptoms were gathered over the duration of the study (24 months).
Adverse Event Reporting Description	Adverse events were recorded spontaneously and upon questioning by nurse at MRI for the hour of the MRI. Additional events were recorded at follow up visit within three months of MRI. Additional lab results were studied at follow up visit within three months of MRI. Finally, lab results and clinical adverse events were studied at three interim analyses by data monitoring committee.
Arm/Group Title	Betaseron		Copaxone
Arm/Group Description	Betaseron 250 micrograms SQ every other day Betaseron: Betaseron 250 micrograms injected SQ every other day		20 mg daily SQ Copaxone: Copaxone 20 mg injected SQ every day (glatiramer acetate)
All Cause Mortality
	Betaseron		Copaxone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Betaseron		Copaxone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/36 (19.4%)		7/39 (17.9%)
Blood and lymphatic system disorders
Venous Thromboembolism	0/36 (0%)	0	1/39 (2.6%)	2
Ear and labyrinth disorders
Loss of Hearing	1/36 (2.8%)	1	0/39 (0%)	0
Balance Impairment	0/36 (0%)	0	1/39 (2.6%)	1
Endocrine disorders
Pancreatitis	1/36 (2.8%)	3	0/39 (0%)	0
Gastrointestinal disorders
Gastroenteritis	1/36 (2.8%)	1	0/39 (0%)	0
Gastritis	0/36 (0%)	0	1/39 (2.6%)	1
General disorders
Pain	1/36 (2.8%)	1	0/39 (0%)	0
Injury, poisoning and procedural complications
Pain near IV Site	0/36 (0%)	0	1/39 (2.6%)	1
Nervous system disorders
Myelitis	0/36 (0%)	0	1/39 (2.6%)	1
Pregnancy, puerperium and perinatal conditions
Pregnancy	2/36 (5.6%)	2	1/39 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Malignant Nodule in Lung	0/36 (0%)	0	1/39 (2.6%)	1
Vascular disorders
Aneurysm	1/36 (2.8%)	1	0/39 (0%)	0
Other (Not Including Serious) Adverse Events
	Betaseron		Copaxone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/36 (5.6%)		7/39 (17.9%)
General disorders
Pain/Burning at Injection Site	1/36 (2.8%)	1	2/39 (5.1%)	2
Headache/Dizziness	0/36 (0%)	0	2/39 (5.1%)	2
Pain	1/36 (2.8%)	1	3/39 (7.7%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.