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)

ISRCTN	ISRCTN87885087
DOI	https://doi.org/10.1186/ISRCTN87885087
ClinicalTrials.gov number	NCT00050778
Secondary identifying numbers	CAMMS 223-A1

Submission date: 23/05/2003
Registration date: 27/05/2003
Last edited: 22/03/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Musculoskeletal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Amanda Cox
Scientific

Department of Neurology
3rd Floor, Box 165
Addenbrookes Hospital
Hills Road
Cambridge
CB2 2QQ
United Kingdom

Email	alc1000@medschl.cam.ac.uk

Study information

Study design	Randomised open-label three-arm study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
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)
Study objectives	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(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	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 study start date	01/12/2002
Completion date	01/12/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	334
Key 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)
Key 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
Date of first enrolment	01/12/2002
Date of final enrolment	01/12/2009

Locations

Countries of recruitment

Croatia
England
Poland
Russian Federation
United Kingdom
United States of America

Study participating centre

Addenbrookes Hospital

Cambridge
CB2 2QQ
United Kingdom

Sponsor information

ILEX Oncology, Inc. (USA)
Industry

4545 Horizon Hill Blvd
San Antonio
Texas
78229-2263
United States of America

"ROR"	https://ror.org/027vj4x92

Funders

Funder type

Industry

ILEX Oncology Inc. (USA) - funding study at all participating centres

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Peer reviewed?	Patient-facing?
Basic results			No	No
Results article	results	23/10/2008	Yes	No
Results article	results	01/04/2011	Yes	No
Results article	results	08/12/2011	Yes	No
Results article	results	01/01/2014	Yes	No

Editorial Notes

22/03/2016: added link to results - basic reporting.