Multiple Sclerosis, Relapsing-Remitting
Conditions
Keywords
Multiple Sclerosis, Relapsing-Remitting, Interferon-β, Rebif®, Minocycline
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).
Detailed description
Interferon beta-1a is the approved standard therapy in RRMS. The beneficial effects of minocycline in the experimental autoimmune encephalomyelitis (EAE) model and its possible inhibitory effect on the degradation of IFN beta-1a suggest that minocycline treatment may have beneficial effects in MS as add-on therapy in subjects who are on treatment with IFN beta-1a. Adjuvant treatment with minocycline is easy to administer, well tolerated and relatively inexpensive. This is a multicentric, double blind, placebo controlled, randomized, parallel group study. Eligible subjects already started with IFN beta-1a (Rebif®) will be randomized 1:1 for treatment with either minocycline 2\*100 mg daily as add-on therapy or placebo. The subjects will be examined clinically at baseline and after 12, 24, 48, 72 and 96 weeks. Laboratory tests (hematology and clinical chemistry) will be performed at baseline and 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 will be performed in a limited number of subjects in selected centers. OBJECTIVES Primary Objective: The effect of minocycline versus placebo in subjects receiving treatment with IFN beta-1a on the time to the first documented relapse Secondary Objectives: * To estimate the effect of minocycline versus placebo in subjects receiving treatment with IFN beta-1a on the mean number of documented relapses per subject up to year 2 * To estimate, in a limited number of 120 subjects at pre-selected sites, the effect of minocycline versus placebo in subjects receiving treatment with IFN beta-1a on the number of new or enlarging lesions on T2-weighted MRI, changes in brain volume measured on MRI Tertiary Objectives: * Time to onset of disability progression sustained over at least 6 months based on change from baseline in EDSS in subjects with RRMS who recently started treatment with IFN beta-1a. (Disability progression is defined as an increase of: 1.0 point on the EDSS if EDSS was \>= 1.0 at baseline; and 1.5 point on the EDSS if EDSS was 0.0 at baseline) * Time to sustained progression by 2 points in 1 Functional System or 1 point in 2 Functional Systems * The total number of reported relapses (documented and undocumented). An undocumented relapse is defined as the appearance of new symptoms or worsening of an old symptom, in the absence of fever, over at least 24 hours that could be attributed to MS activity, preceded by stability or improvement for at least 30 days * The requirement for treatment with glucocorticoids due to relapses * The time to first relapse * The number of relapse-free (documented and undocumented relapses) subjects without progression * The disease activity measured on the integrated disability status scale (IDSS) * The number of subjects with a permanent loss of disability of 1.0 score on the EDSS, confirmed at 2 consecutive visits with an interval of 6 months * The total area of MS lesions on T1 and T2-weighted MRI * Analyze the safety with respect to the combination of Rebif® and minocycline * Rate of dose reduction of IFN beta-1a (Rebif®) * Relapse severity based on the EDSS and IDSS * Immunological analyses in a limited number of subjects (MRI subgroup) * Frequency of increase of liver enzymes according to World Health Organization (WHO) II criteria
Interventions
DRUGMinocycline
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.
DRUGPlacebo
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.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* 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)
Exclusion criteria
* Subjects with any condition that might give rise to similar symptoms as MS * Subjects who have received any other immunomodulatory or immunosuppressive treatment 6 months prior to inclusion into the trial (the obligatory pre-study 3 months \[+/- 1 month\] period of Rebif® treatment not included) * Subjects who have received mitoxantrone or total lymphoid radiation at any time * Subjects who have received treatment with glucocorticoids or adrenocorticotropic hormone (ACTH) later than 1 month prior to inclusion into the trial * Subjects who have experienced a relapse within 1 month prior to inclusion into the trial * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced First Documented Relapse | Baseline up to 96 weeks (+/- 1 week) or early termination (ET) | 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 \[MS\]). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Documented Relapses | Baseline up to 96 weeks (+/- 1 week) or ET | 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 was \>=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 EDSS which assesses disability in 8 functional systems with overall score ranging from 0 (normal) to 10 (death due to MS). |
| Number of New or Enlarging Lesions on Time Constant 2 (T2) Weighted Magnetic Resonance Imaging (MRI) | Final visit (96 weeks [+/- 1 week]) or ET | Inflammatory disease activity was assessed by MRI measurement of the number of new or enlarging T2 lesions. |
| Changes in Brain Volume Measured on Magnetic Resonance Imaging (MRI) | Screening , final visit (96 weeks [+/- 1 week]) or ET | Changes in brain volume were measured as the brain parenchymal fraction using MRI scans. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Relapse Count | Week 48 (+/- 1 week) or ET | A relapse was 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. |
| Number of Relapse Free Participants Without Progression | Baseline up to 96 weeks (+/- 1 week) or ET | Analysis based on documented relapses (relapse: development of new/exacerbation of existing neurological symptoms, persisting for \>48 hrs and with previous period for \>30 days with stable/improving condition; relapse documented by exacerbation \>=1 point increase in 2 functional systems/2 points increase in 1 functional system, or \>=0.5 point increase on EDSS which assesses disability in 8 functional systems with overall score ranging from 0 \[normal\] to 10 \[death due to MS\]) and overall relapses (documented and undocumented relapses); undocumented relapses only fulfilled condition for relapse. |
| Number of Participants With Onset of Disability Progression | Baseline up to 96 weeks (+/- 1 week) or ET | Disability progression was defined as an increase, compared to baseline evaluation of \>= 1.0 points on EDSS if EDSS was \>= 1.0 at baseline or \>=1.5 point on EDSS if EDSS was 0.0 at baseline. EDSS assesses disability in 8 functional systems with overall score ranging from 0 (normal) to 10 (death due to MS). |
| Relapse Severity Based on Expanded Disability Status Scale (EDSS) | 96 weeks (+/- 1 week) or ET | EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. EDSS progression was defined as increase by at least 1 point if last value of EDSS was equal to 5.5 and by at least 0.5 points if last EDSS was more than 5.5. |
| Number of Participants With Total Number of Reported Relapses (Documented and Undocumented Relapses) | Baseline up to 96 weeks (+/- 1 week) or ET | Documented relapses (relapse: development of new/exacerbation of existing neurological symptoms, persisting for \>48 hrs and with previous period for \>30 days with stable/improving condition; relapse documented by exacerbation \>=1 point increase in 2 functional systems/2 points increase in 1 functional system, or \>=0.5 point increase on EDSS which assesses disability in 8 functional systems with overall score ranging from 0 \[normal\] to 10 \[death due to MS\]) and undocumented relapses only fulfilled condition for relapse. |
| Number of Time Constant 2 (T2) Active Lesions | Week 48 up to Week 96 (+/- 1 week) or ET | Inflammatory disease activity was assessed by MRI measurement of the number of T2 active lesions. |
| Percentage of Time Constant 2 (T2) Active Scans Per Participant | Baseline up to 96 weeks (+/- 1 week) or ET | Inflammatory disease activity was assessed by MRI measurement of the percentage of T2 active scans. |
| Burden of Disease | Baseline up to 96 weeks (+/- 1 week) or ET | The burden of disease (BOD) is the total area of MS lesions (abnormal plaques) in the brain measured on Time Constant 1 (T1) or T2 weighted MRI. |
Countries
Denmark
Participant flow
Pre-assignment details
One out of 305 participants was randomized by mistake and did not receive study medication.
Participants by arm
| Arm | Count |
|---|---|
| Rebif®+ Minocycline Participants who self-administered Rebif® (interferon beta-1 alpha \[IFN beta-1a\]) 44 microgram (mcg) as subcutaneous (sc) injection thrice weekly also received minocycline 100 milligram (mg) tablet twice daily as an add-on therapy in accordance with clinical practice for 96 weeks. | 149 |
| Rebif® + Placebo Participants who self-administered Rebif® (IFN beta-1a) 44 mcg as sc injection thrice weekly also received placebo tablets twice daily for 96 weeks. | 155 |
| Total | 304 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 47 | 31 |
| Overall Study | Lack of Efficacy | 2 | 12 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Other | 11 | 14 |
| Overall Study | Planning to become pregnant/pregnancy | 1 | 0 |
| Overall Study | Protocol Violation | 3 | 5 |
| Overall Study | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | Rebif®+ Minocycline | Rebif® + Placebo | Total |
|---|---|---|---|
| Age, Continuous | 36.2 years STANDARD_DEVIATION 8.8 | 37.7 years STANDARD_DEVIATION 8.6 | 37.0 years STANDARD_DEVIATION 8.7 |
| Sex: Female, Male Female | 96 Participants | 102 Participants | 198 Participants |
| Sex: Female, Male Male | 53 Participants | 53 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 51 / 149 | 35 / 155 |
| serious Total, serious adverse events | 11 / 149 | 21 / 155 |
Outcome results
Primary
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 \[MS\]).
Time frame: Baseline up to 96 weeks (+/- 1 week) or early termination (ET)
Population: The Intention to Treat (ITT) population included all the participants who were randomized and received study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rebif®+ Minocycline | Number of Participants Who Experienced First Documented Relapse | 32 participants |
| Rebif® + Placebo | Number of Participants Who Experienced First Documented Relapse | 39 participants |
Secondary
Changes in Brain Volume Measured on Magnetic Resonance Imaging (MRI)
Changes in brain volume were measured as the brain parenchymal fraction using MRI scans.
Time frame: Screening , final visit (96 weeks [+/- 1 week]) or ET
Population: Sub-group of ITT population included limited number of participants at pre-selected sites selected on basis of availability of MRI scanning facilities and the willingness of the site to participate.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rebif®+ Minocycline | Changes in Brain Volume Measured on Magnetic Resonance Imaging (MRI) | -2997.4 cubic millimeter (mm^3) | Standard Deviation 25799.3 |
| Rebif® + Placebo | Changes in Brain Volume Measured on Magnetic Resonance Imaging (MRI) | 5834.9 cubic millimeter (mm^3) | Standard Deviation 20809.4 |
Secondary
Number of New or Enlarging Lesions on Time Constant 2 (T2) Weighted Magnetic Resonance Imaging (MRI)
Inflammatory disease activity was assessed by MRI measurement of the number of new or enlarging T2 lesions.
Time frame: Final visit (96 weeks [+/- 1 week]) or ET
Population: Sub-group of ITT population included limited number of participants at pre-selected sites selected on basis of availability of MRI scanning facilities and the willingness of the site to participate.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rebif®+ Minocycline | Number of New or Enlarging Lesions on Time Constant 2 (T2) Weighted Magnetic Resonance Imaging (MRI) | 3.0 lesions | Standard Deviation 3.3 |
| Rebif® + Placebo | Number of New or Enlarging Lesions on Time Constant 2 (T2) Weighted Magnetic Resonance Imaging (MRI) | 3.0 lesions | Standard Deviation 4.6 |
Secondary
Number of Participants With Documented Relapses
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 was \>=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 EDSS which assesses disability in 8 functional systems with overall score ranging from 0 (normal) to 10 (death due to MS).
Time frame: Baseline up to 96 weeks (+/- 1 week) or ET
Population: ITT population included all the participants who were randomized and received study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rebif®+ Minocycline | Number of Participants With Documented Relapses | 1 | 27 participants |
| Rebif®+ Minocycline | Number of Participants With Documented Relapses | 3 | 2 participants |
| Rebif®+ Minocycline | Number of Participants With Documented Relapses | 2 | 2 participants |
| Rebif®+ Minocycline | Number of Participants With Documented Relapses | 4 | 1 participants |
| Rebif®+ Minocycline | Number of Participants With Documented Relapses | 0 | 117 participants |
| Rebif® + Placebo | Number of Participants With Documented Relapses | 4 | 1 participants |
| Rebif® + Placebo | Number of Participants With Documented Relapses | 0 | 116 participants |
| Rebif® + Placebo | Number of Participants With Documented Relapses | 1 | 29 participants |
| Rebif® + Placebo | Number of Participants With Documented Relapses | 2 | 9 participants |
| Rebif® + Placebo | Number of Participants With Documented Relapses | 3 | 0 participants |
Other Pre-specified
Burden of Disease
The burden of disease (BOD) is the total area of MS lesions (abnormal plaques) in the brain measured on Time Constant 1 (T1) or T2 weighted MRI.
Time frame: Baseline up to 96 weeks (+/- 1 week) or ET
Population: Sub-group of ITT population included limited number of participants at pre-selected sites selected on basis of availability of MRI scanning facilities and the willingness of the site to participate.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rebif®+ Minocycline | Burden of Disease | Total area of lesions on T1 weighted MRI | 1599.4 square millimeter (mm^2) | Standard Deviation 3196.3 |
| Rebif®+ Minocycline | Burden of Disease | Total area of lesions on T2 weighted MRI | 4813.9 square millimeter (mm^2) | Standard Deviation 8385.5 |
| Rebif® + Placebo | Burden of Disease | Total area of lesions on T1 weighted MRI | 1716.8 square millimeter (mm^2) | Standard Deviation 2145.5 |
| Rebif® + Placebo | Burden of Disease | Total area of lesions on T2 weighted MRI | 5717.3 square millimeter (mm^2) | Standard Deviation 6587 |
Other Pre-specified
Number of Participants With Onset of Disability Progression
Disability progression was defined as an increase, compared to baseline evaluation of \>= 1.0 points on EDSS if EDSS was \>= 1.0 at baseline or \>=1.5 point on EDSS if EDSS was 0.0 at baseline. EDSS assesses disability in 8 functional systems with overall score ranging from 0 (normal) to 10 (death due to MS).
Time frame: Baseline up to 96 weeks (+/- 1 week) or ET
Population: ITT population included all the participants who were randomized and received study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rebif®+ Minocycline | Number of Participants With Onset of Disability Progression | 6 participants |
| Rebif® + Placebo | Number of Participants With Onset of Disability Progression | 3 participants |
Other Pre-specified
Number of Participants With Total Number of Reported Relapses (Documented and Undocumented Relapses)
Documented relapses (relapse: development of new/exacerbation of existing neurological symptoms, persisting for \>48 hrs and with previous period for \>30 days with stable/improving condition; relapse documented by exacerbation \>=1 point increase in 2 functional systems/2 points increase in 1 functional system, or \>=0.5 point increase on EDSS which assesses disability in 8 functional systems with overall score ranging from 0 \[normal\] to 10 \[death due to MS\]) and undocumented relapses only fulfilled condition for relapse.
Time frame: Baseline up to 96 weeks (+/- 1 week) or ET
Population: ITT population included all the participants who were randomized and received study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rebif®+ Minocycline | Number of Participants With Total Number of Reported Relapses (Documented and Undocumented Relapses) | 0 | 107 participants |
| Rebif®+ Minocycline | Number of Participants With Total Number of Reported Relapses (Documented and Undocumented Relapses) | 1 | 30 participants |
| Rebif®+ Minocycline | Number of Participants With Total Number of Reported Relapses (Documented and Undocumented Relapses) | 2 | 6 participants |
| Rebif®+ Minocycline | Number of Participants With Total Number of Reported Relapses (Documented and Undocumented Relapses) | 3 | 4 participants |
| Rebif®+ Minocycline | Number of Participants With Total Number of Reported Relapses (Documented and Undocumented Relapses) | 4 | 1 participants |
| Rebif®+ Minocycline | Number of Participants With Total Number of Reported Relapses (Documented and Undocumented Relapses) | 5 | 1 participants |
| Rebif® + Placebo | Number of Participants With Total Number of Reported Relapses (Documented and Undocumented Relapses) | 4 | 0 participants |
| Rebif® + Placebo | Number of Participants With Total Number of Reported Relapses (Documented and Undocumented Relapses) | 0 | 96 participants |
| Rebif® + Placebo | Number of Participants With Total Number of Reported Relapses (Documented and Undocumented Relapses) | 3 | 3 participants |
| Rebif® + Placebo | Number of Participants With Total Number of Reported Relapses (Documented and Undocumented Relapses) | 1 | 38 participants |
| Rebif® + Placebo | Number of Participants With Total Number of Reported Relapses (Documented and Undocumented Relapses) | 5 | 1 participants |
| Rebif® + Placebo | Number of Participants With Total Number of Reported Relapses (Documented and Undocumented Relapses) | 2 | 17 participants |
Other Pre-specified
Number of Relapse Free Participants Without Progression
Analysis based on documented relapses (relapse: development of new/exacerbation of existing neurological symptoms, persisting for \>48 hrs and with previous period for \>30 days with stable/improving condition; relapse documented by exacerbation \>=1 point increase in 2 functional systems/2 points increase in 1 functional system, or \>=0.5 point increase on EDSS which assesses disability in 8 functional systems with overall score ranging from 0 \[normal\] to 10 \[death due to MS\]) and overall relapses (documented and undocumented relapses); undocumented relapses only fulfilled condition for relapse.
Time frame: Baseline up to 96 weeks (+/- 1 week) or ET
Population: ITT population included all the participants who were randomized and received study medication. Number of participants analyzed N included those participants who were evaluated for this particular measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rebif®+ Minocycline | Number of Relapse Free Participants Without Progression | Relapse free participants (documented relapse) | 105 participants |
| Rebif®+ Minocycline | Number of Relapse Free Participants Without Progression | Relapse free participants (overall relapse) | 96 participants |
| Rebif® + Placebo | Number of Relapse Free Participants Without Progression | Relapse free participants (documented relapse) | 108 participants |
| Rebif® + Placebo | Number of Relapse Free Participants Without Progression | Relapse free participants (overall relapse) | 89 participants |
Other Pre-specified
Number of Time Constant 2 (T2) Active Lesions
Inflammatory disease activity was assessed by MRI measurement of the number of T2 active lesions.
Time frame: Week 48 up to Week 96 (+/- 1 week) or ET
Population: Data was not analyzed due to insufficient number of participants available for the analysis of this measure and the study was prematurely terminated.
Other Pre-specified
Percentage of Time Constant 2 (T2) Active Scans Per Participant
Inflammatory disease activity was assessed by MRI measurement of the percentage of T2 active scans.
Time frame: Baseline up to 96 weeks (+/- 1 week) or ET
Population: Data was not analyzed due to insufficient number of participants available for the analysis of this measure and the study was prematurely terminated.
Other Pre-specified
Relapse Count
A relapse was 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.
Time frame: Week 48 (+/- 1 week) or ET
Population: Data was not analyzed due to insufficient number of participants available for the analysis of the measure and the study was prematurely terminated.
Other Pre-specified
Relapse Severity Based on Expanded Disability Status Scale (EDSS)
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. EDSS progression was defined as increase by at least 1 point if last value of EDSS was equal to 5.5 and by at least 0.5 points if last EDSS was more than 5.5.
Time frame: 96 weeks (+/- 1 week) or ET
Population: ITT population included all the participants who were randomized to study medication. Number of participants analyzed N included those participants who were evaluated for this particular measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rebif®+ Minocycline | Relapse Severity Based on Expanded Disability Status Scale (EDSS) | 1.90 Units on a scale | Standard Deviation 1.38 |
| Rebif® + Placebo | Relapse Severity Based on Expanded Disability Status Scale (EDSS) | 2.02 Units on a scale | Standard Deviation 1.42 |