Minocycline as add-on to Interferon Beta-1a [IFN Beta-1a] (Rebif®) in Relapsing-Remitting Multiple Sclerosis [RRMS]

NCT01134627 | Terminated Phase 2 Results DMC

• 2 other identifiers: IMP 265882005-004289-18
• Study Type: interventional
• Target: 305
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicentric, double-blind, placebo-controlled, randomized, parallel group study to estimate the effect of minocycline as add-on to interferon beta-1a (IFN beta-1a) in subjects with relapsing-remitting multiple sclerosis (RRMS).

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

Multiple Sclerosis, Relapsing-Remitting; Interferon-β; Rebif®; Minocycline

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Experienced First Documented Relapse

  Documented relapse: development of new/exacerbation of existing neurological symptoms, persisting for \>48 hrs and with previous period for \>30 days with stable/improving condition. Exacerbation = at least (\>=)1 point increase in 2 functional systems/2 points increase in 1 system,either in pyramidal, cerebral, brain-stem, sensory, bowel and bladder, visual, cerebral or other functional system or \>=0.5 point increase on expanded disability status scale (EDSS) which assesses disability in 8 functional systems with overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis \[MS\]).

  Baseline up to 96 weeks (+/- 1 week) or early termination (ET)

Secondary Outcomes (3)

• Number of Participants With Documented Relapses

  Baseline up to 96 weeks (+/- 1 week) or ET

• Number of New or Enlarging Lesions on Time Constant 2 (T2) Weighted Magnetic Resonance Imaging (MRI)

  Final visit (96 weeks [+/- 1 week]) or ET

• Changes in Brain Volume Measured on Magnetic Resonance Imaging (MRI)

  Screening , final visit (96 weeks [+/- 1 week]) or ET

Other Outcomes (8)

• Number of Participants With Onset of Disability Progression

  Baseline up to 96 weeks (+/- 1 week) or ET

• Number of Time Constant 2 (T2) Active Lesions

  Week 48 up to Week 96 (+/- 1 week) or ET

• Percentage of Time Constant 2 (T2) Active Scans Per Participant

  Baseline up to 96 weeks (+/- 1 week) or ET

Study Arms (2)

Minocycline group

EXPERIMENTAL

Drug: Minocycline

Placebo Group

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Minocycline DRUG

Participants who are self-administering Rebif® (IFN beta-1a) 44 microgram (mcg) as subcutaneous (sc) injection thrice weekly will also receive minocycline 100 milligram (mg) tablet twice daily as an add-on therapy in accordance with clinical practice for 96 weeks.

Minocycline group

Placebo DRUG

Participants who are self-administering Rebif® (IFN beta-1a) 44 mcg as sc injection thrice weekly will also receive placebo tablets twice daily for 96 weeks.

Placebo Group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects who have given 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 subject
• Subjects with stable disease without relapses in the last 30 days
• Subjects aged between 18 and 55 years (both included)
• Subjects who suffer from definite RRMS according to Poser criteria (clinical definite multiple sclerosis \[CDMS\] or laboratory supported definite multiple sclerosis \[LSDMS\]) or definite MS according to McDonald criteria
• Subjects who have started treatment with Rebif® 44 mcg 3 months ago (+/- 1 month) including the titration phase
• Subjects who have a disability equivalent to an EDSS of 5.5 or less
• Subjects who have shown clinical activity defined as at least 1 documented relapse within the last year (A documented relapse is defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, persisting for more than 48 hours and with a previous period for more than 30 days with a stable or an improving condition. The exacerbation must be equivalent to an increase of at least 1 point in 2 functional systems or to an increase of 2 points in 1 system, either in the pyramidal, cerebellar, brain-stem, sensory, bowel and bladder, visual, cerebral or other functional system or an increase of at least half a point on the EDSS. Changes in bowel and bladder or cerebral functions should not solely be responsible for documentation of a relapse. The relapses must have been evaluated by a neurologist, retrospectively if necessary)
• Subjects 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
• Female subjects must either: be post-menopausal or surgically sterilized; or use a hormonal contraceptive or intra-uterine device (only following contraceptives are allowed: birth control pills, intra-uterine device, depot injection of gestagen, subdermal implant, hormonal vaginal ring and transdermal depot patches); or be sexually inactive for the duration of the study, and be neither pregnant nor breast-feeding (confirmation that the subject is not pregnant must be established by a negative serum human chorionic gonadotropin (hCG) pregnancy test within 28 days of Study Day 1 and a negative urine pregnancy test on Study Day 1. A pregnancy test is not required if the subject is post-menopausal or surgically sterilized)

You may not qualify if:

• Subjects with any condition that might give rise to similar symptoms as MS
• Subjects who have received mitoxantrone or total lymphoid radiation at any time
• Subjects who have suffered from major depression
• Subjects with alcohol or drug dependency
• Subjects with cardiac insufficiency, cardiomyopathy, significant cardiac dysrhythmias, unstable or advanced ischemic heart disease (New York Heart Association \[NYHA\] grade III or IV), or significant hypertension (Blood Pressure \> 180/110 millimeter of mercury \[mmHg\])
• Subjects with renal insufficiency defined as serum creatinine \> 1.5 times the upper normal reference limit
• Subjects with alanine aminotransferase (ALAT) and asparagine aminotransferase (ASAT) (or either 1 if only 1 of the 2 is measured) levels more than 2 times the normal upper reference limit.
• Subjects with leucopoenia \< 2500 per microliter (microL) or thrombopenia \< 100000 per microL
• Subjects with any medical illness requiring treatment with systemic corticosteroids
• Subjects with any systemic disease that can influence the subject's safety and compliance, or the evaluation of the disability
• Female subjects who are pregnant or breastfeeding or who plan to become pregnant during the study
• Subjects with known or suspected allergy to minocycline or other tetracyclines
• Subjects who have participated in any other studies, involving other investigational products, within 30 days prior to participating in this trial

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Scleroseklinikken afsnit 2082

Copenhagen, 2100, Denmark

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; cyclopia sequence

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Per Soelberg Sørensen, Professor

  Rigshospitalet,Blegdamsvej 9, 2100 København Ø, Scleroseklinikken afsnit 2082

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2010
• First Posted: June 2, 2010
• Study Start: February 1, 2006
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: December 27, 2013
• Results First Posted: September 5, 2012

Record last verified: 2013-12

Locations

DK (1)