Contact information
Type
Scientific
Primary contact
Dr Amanda Cox
ORCID ID
Contact details
Department of Neurology
3rd Floor
Box 165
Addenbrookes Hospital
Hills Road
Cambridge
CB2 2QQ
United Kingdom
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alc1000@medschl.cam.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00050778
Protocol/serial number
CAMMS 223-A1
Study information
Scientific title
A phase II, randomised, open-label, three-arm study comparing low-and high-dose Campath® (MabCampath®) and high-dose Rebif® in patients with early, active relapsing-remitting Multiple Sclerosis (MS)
Acronym
Study hypothesis
To compare low-and high-dose Campath® and high-dose Rebif® in patients with early, active relapsing-remitting Multiple Sclerosis (MS) who have not been previously treated with immunotherapies other than steroids.
Ethics approval
Not provided at time of registration
Study design
Randomised open-label three-arm study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Relapsing-remitting multiple sclerosis
Intervention
Patients will be randomised to receive lower- or higher-dose Campath® or Rebif® as controlled by the Interactive Voice Response System (IVRS) for all study sites. Randomisation will be accomplished by utilising the minimisation (adaptive randomisation) method described by Pocock and Simon, using a randomisation probability parameter of 0.80.
Patients will be allocated to treatment arm according to a set of pre-defined variables that will ensure a balanced population among the three treatment arms. The process of minimisation is superior to conventional randomisation in that optimal balance can be achieved over a larger number of variables than can otherwise occur through conventional stratified randomisation. The system will be tested and validated according to standard life cycle development process guidelines.
This randomisation methodology will ensure balance among treatment arms with respect to the following baseline factors:
1. Study centre
2. Sex
3. Age:
3.1. Less than 30
3.2. Greater than 30
4. Baseline EDSS score:
4.1. Less than 2.0
4.2. Greater than or equal to 2
Intervention type
Drug
Phase
Phase II
Drug names
Campath®, Rebif®
Primary outcome measure
1. Time to sustained accumulation of disability (SAD)
2. Relapse rate
Secondary outcome measures
1. Proportion of patients who are relapse free at 3 years after initial treatment
2. MRI T1 to determine rate of cerebral atrophy (decrease in cerebral volume) as seen on MRI brain scan as measured by the Losseff technique at 3 years after initial treatment
3. Change in MRI T2 lesion volume at 3 years after initial treatment
Overall trial start date
01/12/2002
Overall trial end date
01/12/2009
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Signed, written informed consent
2. Male or non-pregnant, non-lactating female patients, 18 to 50 years of age (inclusive)
3. Diagnosis of MS per McDonald's update of the Poser criteria, including cranial Magnetic Resonance Imaging (MRI) consistent with those criteria
4. Onset of first symptoms within 3 years prior to screening
5. Expanded Disability Status Scale (EDSS) score 0.0 - 3.0 (inclusive) at the screening and baseline visits
6. At least two clinical episodes of MS in the 2 years prior to study entry (i.e., the initial event if within 2 years of study entry plus greater than or equal to one relapse, or greater than or equal to two relapses if the initial event was between 2 and 3 years prior to study entry)
7. In addition to the clinical criteria (3 to 6 above), greater than or equal to one enhancing lesion on any one of the up to four screening gadolinium-enhanced MRI brain scans during a maximum 3-month run-in period (inclusive of the Month 0 baseline scan)
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
334
Participant exclusion criteria
1. Previous immunotherapy for MS other than steroids, including treatment with interferons, intravenous immunoglobulin, glatiramer acetate, and mitoxantrone
2. Personal history of thyroid autoimmune disease
3. Personal history of clinically significant autoimmune disease (e.g., inflammatory bowel disease, diabetes, lupus, severe asthma)
4. History of thyroid carcinoma (previous thyroid adenoma is acceptable and is not to be considered an exclusion criterion)
5. History of malignancy (except for basal cell skin carcinoma in which situation the patient is eligible only if disease-free for more or equal to 5 years)
6. Any disability acquired from trauma or another illness that, in the opinion of the investigator, could interfere with evaluation of disability due to MS
7. Previous treatment with Campath®
8. History of anaphylaxis following exposure to humanized monoclonal antibodies
9. Inability to undergo MRI with gadolinium administration
10. Female patients with childbearing potential with a positive serum pregnancy test at screening or baseline. (NB: Serum pregnancy testing will be performed on each occasion)
11. Male and female patients who do not agree to use effective contraceptive method(s) during the study
12. Impaired renal function (i.e., serum creatinine larger or equal to 2 times the institutional Upper Limit of Normal [ULN])
13. Untreated Major Depressive Disorder (MDD)
14. Epileptic seizures that are not adequately controlled by treatment
15. Suicidal ideation
16. Major systemic disease or other illness that would, in the opinion of the investigator, compromise patient safety or interfere with the interpretation of study results
17. Abnormal CD4 count or significantly abnormal thyroid function; presence of anti-Thyroid Stimulating Hormone (TSH) receptor antibodies; known seropositivity for Human Immunodeficiency Virus (HIV)
18. Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
19. Presence of a monoclonal paraprotein
20. Patients who, in the opinion of the investigator, have any form of MS other than relapsing-remitting
21. Patients currently participating in a clinical trial of an experimental or unapproved/unlicensed therapy
Recruitment start date
01/12/2002
Recruitment end date
01/12/2009
Locations
Countries of recruitment
Croatia, Poland, Russian Federation, United Kingdom, United States of America
Trial participating centre
Addenbrookes Hospital
Cambridge
CB2 2QQ
United Kingdom
Funders
Funder type
Industry
Funder name
ILEX Oncology Inc. (USA) - funding study at all participating centres
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
See https://clinicaltrials.gov/ct2/show/results/NCT00050778
Publication list
2008 results in: http://www.ncbi.nlm.nih.gov/pubmed/18946064
2011 results in: http://www.ncbi.nlm.nih.gov/pubmed/21397567
2011 results in: http://www.ncbi.nlm.nih.gov/pubmed/21960587
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24170099
Publication citations
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Results
Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK, Alemtuzumab vs. interferon beta-1a in early multiple sclerosis, N. Engl. J. Med., 2008, 359, 17, 1786-1801, doi: 10.1056/NEJMoa0802670.
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Results
Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Bass AD, Wynn DR, Margolin DH, Lake SL, Moran S, Palmer J, Smith MS, Compston DA, Alemtuzumab versus interferon β-1a in early relapsing-remitting multiple sclerosis: post-hoc and subset analyses of clinical efficacy outcomes., Lancet Neurol, 2011, 10, 4, 338-348, doi: 10.1016/S1474-4422(11)70020-5.
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Results
Cuker A, Coles AJ, Sullivan H, Fox E, Goldberg M, Oyuela P, Purvis A, Beardsley DS, Margolin DH, A distinctive form of immune thrombocytopenia in a phase 2 study of alemtuzumab for the treatment of relapsing-remitting multiple sclerosis., Blood, 2011, 118, 24, 6299-6305, doi: 10.1182/blood-2011-08-371138.
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Results
Daniels GH, Vladic A, Brinar V, Zavalishin I, Valente W, Oyuela P, Palmer J, Margolin DH, Hollenstein J, Alemtuzumab-related thyroid dysfunction in a phase 2 trial of patients with relapsing-remitting multiple sclerosis., J. Clin. Endocrinol. Metab., 2014, 99, 1, 80-89, doi: 10.1210/jc.2013-2201.