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

Condition(s) targeted: Relapsing-Remitting Multiple Sclerosis

Intervention: Minocycline (Drug); Placebo (Other)

Phase: Phase 2

Status: Recruiting

Sponsored by: EMD Serono

Official(s) and/or principal investigator(s):
David Bénée Olsen, MD, Study Director, Affiliation: Serono Nordic AB, Merck Serono International S.A., an affiliate of Merck KGaA, Darmstadt, Germany

Overall contact:
Medical Information Office - Denmark, Phone: +45 35 25 3550

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

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

Study design: Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: The time to the first documented MS relapse

Secondary outcome: 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.

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.

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

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.

Medical Information Office - Denmark, Phone: +45 35 25 3550

Research Site, Copenhagen, Denmark; Recruiting
Phone: +45 35 25 35 50

Research Site, Helsinki, Finland; Recruiting
Phone: +358 9 867 87063

Research Site, Lyon, France; Recruiting
Phone: +33 437 53 22 19

Research Site, Oslo, Norway; Recruiting
Phone: +47 679 03 590

Research Site, Stockholm, Sweden; Recruiting
Phone: +46 85 62 44 500

Research Site, Zug, Switzerland; Recruiting
Phone: +41 41 729 22 24

Full FDA approved prescribing information can be found here

Starting date: March 2006
Last updated: March 21, 2009