Minocycline as Add-on to Interferon-Beta-1a (Rebif®) in RRMS (Recycline) - Full Text View

Sponsor:	EMD Serono
Information provided by:	EMD Serono
ClinicalTrials.gov Identifier:	NCT00381459

Purpose

A Multi-centre, Double Blind, Randomised, Placebo Controlled, Parallel Group Trial Investigating Minocycline versus placebo as add-on therapy in patients who are on treatment with Interferon-beta-1a 44mcg tiw (Rebif®) for the Treatment of Relapsing-Remitting Multiple Sclerosis

Condition	Intervention	Phase
Relapsing-Remitting Multiple Sclerosis	Drug: Minocycline Other: Placebo	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	A Multi-Centre, Double Blind, Randomised, Placebo Controlled, Parallel Group Trial Investigating Minocycline Versus Placebo as Add-on Therapy in Patients Who Are on Treatment With Interferon-Beta-1a 44mcg Tiw (Rebif®) for the Treatment of Relapsing-Remitting Multiple Sclerosis

Resource links provided by NLM:

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Minocycline Minocycline hydrochloride Interferon beta Interferon-beta Interferon beta 1a Interferons

U.S. FDA Resources

Further study details as provided by EMD Serono:

Primary Outcome Measures:

The time to the first documented MS relapse [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

The mean number of relapses per patient up to year 2. And in a limited number of 120 patients: The number of new or enlarging lesions on T2 weighted MRI. Changes in brain volume measured on MRI. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	320
Study Start Date:	March 2006
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: Minocycline 100mg bid (twice daily)
2: Placebo Comparator	Other: Placebo Placebo 100mg bid (twice daily)

Detailed Description:

Study design Minocycline, a tetracycline derivative, has shown immunomodulatory properties. In smaller clinical trials in patients with multiple sclerosis treatment with minocycline reduced MRI measured disease activity.

This is a multi-centre, double blind, placebo controlled, randomised, parallel group study. Eligible patients already started with IFN-beta-1a (Rebif®) will be randomised for treatment with either minocycline 200 mg daily as add-on therapy or placebo. The patients will be examined clinically at baseline and after 12, 24, 48, 72 and 96 weeks. Laboratory tests will be performed at baseline, after 4, 8, 12, 24, 36, 48, 60, 72, 84 and 96 weeks (At 4, 8, 36, 60 and 84 weeks only an additional liver enzyme test will be scheduled). The MRI (T1-weighted and T2-weighted) before treatment and after 96 weeks and immunological studies before treatment and after 48 weeks are performed in a limited number of patients in selected centers.

Patients with definite relapsing-remitting multiple sclerosis who have never received treatment with interferons or glatiramer acetate and have only recently been started on IFN-beta-1a (Rebif®) for 3 months (± 1 month), who meet all the eligibility criteria. The patients will be recruited from the outpatient clinics of the participating neurological departments among patients who recently started treatment with interferon-beta-1a. It is estimated that 340 patients with RRMS and treated with Rebif 44 mcg tiw for 3 (± 1 month) will be screened to provide 320 enrolled subjects. Subjects will be recruited from approximately 47 centres in the 4 Nordic countries in France and Switzerland. MRI and Immunological testing will only be performed in around 120 patients in 10-13 selected centers.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

The patient must give written informed consent prior to any trial related activities. Trial related activities are any procedures that would not have been performed during normal management of the patient.
Have stable disease without relapses in the last 30 days.
Is between the age of 18 and 55 years (both included).
Suffers from definite relapsing-remitting MS according to Poser criteria (CDMS or LSDMS) or definite MS according to McDonald criteria.
Has started treatment with Rebif 44 3 months ago (± 1 month).
Has a disability equivalent to an EDSS of 5.5 or less.
Has shown clinical activity defined as at least one documented relapse within the last year.
The patient must be prepared to and considered able to follow the protocol during the whole trial period and to attend the planned visits, even if the treatment has to be withdrawn.

Exclusion Criteria:

Any condition that might give rise to similar symptoms as MS.
Has received any other immunomodulatory or immunosuppressive treatment than Rebif six months prior to inclusion into the trial.
Has received mitoxantrone or total lymphoid radiation at any time.
Has received treatment with glucocorticoids or ACTH later than one month prior to inclusion into the trial.
Has experienced a relapse within one month prior to inclusion into the trial.
Has suffered from major depression.
Alcohol or drug dependency.
Has cardiac insufficiency, cardiomyopathy, significant cardiac dysrhythmia, unstable or advanced ischemic heart disease (NYHA III or IV), or significant hypertension (BP > 180/110 mmHg).
Has renal insufficiency defined as serum creatinine > 1.5 times the upper normal reference limit.
ALAT and ASAT (or either one if only one of the two is measured) more than 2 times the normal upper reference limit.
Leucopoenia < 2500 per microl or thrombopenia < 100000 per microl.
Any medical illness requiring treatment with systemic corticosteroids.
Any systemic disease that can influence the patient's safety and compliance, or the evaluation of the disability.
Women who are pregnant or breastfeeding or who plan to become pregnant during the study.
Known or suspected allergy to minocycline or other tetracyclines. Participation in any other studies, involving other investigational products, within 30 days prior to participating in this trial.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00381459

Contacts

Contact: Medical Information Office - Denmark

+45 35 25 3550

Locations

Denmark
Research Site	Recruiting
Copenhagen, Denmark
Contact +45 35 25 35 50
Finland
Research Site	Recruiting
Helsinki, Finland
Contact +358 9 867 87063
France
Research Site	Recruiting
Lyon, France
Contact +33 437 53 22 19
Norway
Research Site	Recruiting
Oslo, Norway
Contact +47 679 03 590
Sweden
Research Site	Recruiting
Stockholm, Sweden
Contact +46 85 62 44 500
Switzerland
Research Site	Recruiting
Zug, Switzerland
Contact +41 41 729 22 24

Sponsors and Collaborators

EMD Serono

Investigators

Study Director:

David Bénée Olsen, MD

Serono Nordic AB, Merck Serono International S.A., an affiliate of Merck KGaA, Darmstadt, Germany

More Information

Additional Information:

Full FDA approved prescribing information can be found here This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Serono Nordic AB, Merck Serono International S.A., an affiliate of Merck KGaA, Darmstadt, Germany ( David Bénée Olsen, MD, International Project Leader )
Study ID Numbers:	26588
Study First Received:	September 26, 2006
Last Updated:	March 21, 2009
ClinicalTrials.gov Identifier:	NCT00381459 History of Changes
Health Authority:	Sweden: Regional Ethical Review Board

Additional relevant MeSH terms:

Anti-Infective Agents
Minocycline
Autoimmune Diseases
Immunologic Factors
Demyelinating Diseases
Immune System Diseases
Antineoplastic Agents
Physiological Effects of Drugs
Nervous System Diseases
Adjuvants, Immunologic
Interferon-beta

Sclerosis
Antiviral Agents
Multiple Sclerosis, Relapsing-Remitting
Pharmacologic Actions
Anti-Bacterial Agents
Multiple Sclerosis
Pathologic Processes
Therapeutic Uses
Interferon beta 1a
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System

ClinicalTrials.gov processed this record on February 08, 2010