Multiple SclerosisPhase 4BECOMENCT00176592
Phase IV Study, Betaseron Versus Copaxone for Relapsing Remitting or CIS Forms of MS Using Triple Dose Gad 3 T MRI
A Phase 4 study testing Betaseron and Copaxone in people with Multiple Sclerosis, run by University of Medicine and Dentistry of New Jersey at 1 site in United States.
Trial summary
This is the first comparison of efficacy of Betaseron and Copaxone for treatment of relapsing forms of MS. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Betaseron and Copaxone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2003to Jan 2007
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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:
- 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.
Show all 10Show fewer
- 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.
Who cannot join
- 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.
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
This is the first comparison of efficacy of Betaseron and Copaxone for treatment of relapsing forms of MS.
Read the 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.
- Conditions
- Multiple Sclerosis
- Being tested
- Betaseron, Copaxone
- Keywords
- Multiple Sclerosis, Brain, Betaseron, Copaxone, MRI
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BetaseronDrug
Also called Betaseron 250 mcg SQ every other day, Intaferon beta 1 b
Betaseron 250 micrograms injected SQ every other day
CopaxoneDrug
Also called Copaxone 20 mg injected SQ every day (glatiramer acetate)
Copaxone 20 mg injected SQ every day (glatiramer acetate)
| Study group | Role | What they receive |
|---|---|---|
| Betaseron | Active comparator | Betaseron 250 micrograms SQ every other day and Triple-Dose Gadolinium at each MRI Receives: Drug: Betaseron |
| Copaxone | Active comparator | Copaxone 20 mg daily SQ and Triple-Dose Gadolinium at each MRI Receives: Drug: Copaxone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 2 years
Secondary outcomes (2)
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.
Measured: 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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study startJan 2003
- Primary completionJan 2007
- Study completionJan 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Medicine and Dentistry of New Jersey
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Suhayl Dhib-Jalbut, MD, Rutgers, The State University of New Jersey
- Investigators
- Stuart D Cook, MD, Principal investigator, MD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00176592
- Sponsor's protocol ID
- 0120020167
- Other IDs
- 0120020167
- Acronym
- BECOME
- Status last verified
- Oct 2021
- First submitted
- 13 Sep 2005
- Last updated
- 16 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
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.
PubMed 19279320Cadavid 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.
PubMed 19687024Maranzano 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.
PubMed 28724581
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00176592
- Acronym / sponsor ID
- BECOME / 0120020167
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Brain, Betaseron, Copaxone, MRI
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- University of Medicine and Dentistry of New JerseyUniversity, hospital or other
- Study start
- Jan 2003
- Primary completion
- Jan 2007 (actual)
- Study completion
- Jan 2007 (actual)
- First posted
- 15 Sep 2005 (estimated)
- Results
- Posted 16 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is the first comparison of efficacy of Betaseron and Copaxone for treatment of relapsing forms of MS.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Betaseron | Active comparator | Drug: BetaseronBetaseron 250 micrograms SQ every other day and Triple-Dose Gadolinium at each MRI |
| Copaxone | Active comparator | Drug: CopaxoneCopaxone 20 mg daily SQ and Triple-Dose Gadolinium at each MRI |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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:
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BetaseronAlso: Betaseron 250 mcg SQ every other day, Intaferon beta 1 bBetaseron 250 micrograms injected SQ every other day | Drug | Betaseron |
| CopaxoneAlso: Copaxone 20 mg injected SQ every day (glatiramer acetate)Copaxone 20 mg injected SQ every day (glatiramer acetate) | Drug | Copaxone |
Primary outcome
The Primary Outcome Measure is the Number of "Combined Active Lesions" (CAL) by Monthly MRI at the Conclusion of the Study.
Time frame: 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.
2 secondary outcomes
The Number of Enhancing Lesions.
Time frame: up to 2 years
The Number of MRI Disease Free Patients.
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19279320Cadavid 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.
- Results publication: PubMed 19687024Cadavid 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.
- Derived from this study: PubMed 28724581Maranzano 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stuart D Cook, MD principal investigator
MD
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Betaseron and Copaxone in people with Multiple Sclerosis, run by University of Medicine and Dentistry of New Jersey at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Primary Outcome Measure is the Number of "Combined Active Lesions" (CAL) by Monthly MRI at the Conclusion of the Study. (time frame: up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00176592, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Nov 2021.