Condition category
Musculoskeletal Diseases
Date applied
23/05/2003
Date assigned
27/05/2003
Last edited
22/03/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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
-
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 measures

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

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

Sponsor information

Organisation

ILEX Oncology, Inc. (USA)

Sponsor details

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

Sponsor type

Industry

Website

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

Results - basic reporting

See https://clinicaltrials.gov/ct2/show/results/NCT00050778

Publication summary

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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

Additional files

Editorial Notes

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