A multi-centre randomised study to evaluate the efficacy of Betaferon-interferon-beta-1b (IFNB-1B) 500 mcg therapy in the induction of tolerance to IFNB in MS patients with neutralising antibodies (NAbs) to IFNB-1a (Rebif) - Betaferon NaB Anergy Study

• Register: EUCTR
• Last refreshed on: 3 April 2012
• Main ID: EUCTR2005-005751-18-GB
• Date of registration: 17/02/2006
• Prospective Registration: Yes
• Primary sponsor: UCL Biomedicine R&D Unit
• Public title: A multi-centre randomised study to evaluate the efficacy of Betaferon-interferon-beta-1b (IFNB-1B) 500 mcg therapy in the induction of tolerance to IFNB in MS patients with neutralising antibodies (NAbs) to IFNB-1a (Rebif) - Betaferon NaB Anergy Study
• Scientific title: A multi-centre randomised study to evaluate the efficacy of Betaferon-interferon-beta-1b (IFNB-1B) 500 mcg therapy in the induction of tolerance to IFNB in MS patients with neutralising antibodies (NAbs) to IFNB-1a (Rebif) - Betaferon NaB Anergy Study
• Date of first enrolment: 07/09/2006
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-005751-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: (Rebif) IFNB-1a

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Confirmed diagnosis of MS according to the McDonald criteria (Appendix 1).
Current treatment with Rebif® (22 or 44) s.c. TIW for at least 6 months or more
Two consecutive positive NAb titres of ?20NU at least 4 weeks apart.
Age over 18 years and less than 65 years.
Expanded Disability Status Scale (EDSS) score not to exceed 6.5.
Women of childbearing potential must agree to practice adequate contraception methods, defined as barrier methods with spermicide, surgical sterilisation of self or male partner, combined oral contraceptives or intrauterine device/system. All female subjects who are not post-menopausal or surgically sterile must have a negative blood pregnancy test at screening.
Must give written informed consent and authorise the release and use of protected health information, as required by local law.
Able and willing to undergo blood sampling at regular intervals as defined by the protocol.
Able to comply with study requirements.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Treatment with other immunosuppressive, immunomodulatory, or experimental treatments within the last 6 months of enrollment in the study, but excluding pulsed intravenous or oral steroids for treatment of MS relapse.
Patients presenting a severe or unstable disorder: poorly controlled diabetes, arterial hypertension, severe cardiac insufficiency, unstable ischemic heart disease, clinically significant laboratory abnormality, or any medical condition which, in the opinion of the chief investigator, would pose additional risk in administering IFNß-1b to the patient.
Presence of chronic or recurrent infection.
Exposure to any other investigational drug within 30 days of enrollment in the study.
History of malignancy unless an exception is granted by the Chief Investigator.
History of human immunodeficiency virus (HIV).
History of drug or alcohol abuse within 6 months prior to enrollment into the study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system of unknown aetiology. It is the commonest cause of disability in young adults. The prevalence in the UK is approximately 125/100,000 of the population with an annual incidence of 6/100,000. Approximately 80,000 individuals are affected with MS in the UK.

Intervention(s)

Trade Name: Rebif 44
Product Name: Rebif 44
Product Code: Interferon beta 1a
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Interferon beta 1a
Current Sponsor code: IFNB-1a
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 44-

Trade Name: Rebif 22
Product Name: Rebif 22
Product Code: Interferon beta 1a
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Interferon beta 1a
Current Sponsor code: IFNB-1a
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 22-

Product Name: Betaferon 500mcg
Product Code: Betaferon 500mcg
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Interferon beta 1b
Current Sponsor code: IFNB-1b
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Main Objective: To assess whether switching MS subjects with NAbs induced by IFNß-1a (Rebif® 22µg or 44µg) to 500mcg IFNß-1b (Betaferon®) re-induces tolerance to IFNß, i.e. causes a higher than expected rate of reversion from NAb-positive to NAb-negative.

Primary end point(s): The primary endpoint is time until confirmed NAb-negative status will be assessed, i.e. two consecutive NAb-negative samples taken 3 months apart. This will be compared between the two randomised groups (those taking interferon-beta-1b (Betaferon®) 500mcg subcutaneously every other day)and those remaining on subcutaneous interferon-beta-1a three times a week therapy (Rebif-22 or Rebif-44). The interferon-beta-1b 500 micrograms subcutaneously every other day (Betaferon) treatment group will also be compared with a historical control group treated with interferon-beta-1a 22 or 44 micrograms subcutaneously three times a week.

Secondary Objective: There are no secondary objectives to the trial.

Secondary ID(s)

QS001