Multiple Sclerosis
Conditions
Brief summary
The purpose of this trial is to evaluate the effects of Rebif® 44 mcg subcutaneous (sc) three times a week (tiw) on a) remyelination/demyelination, b) lesion and brain volume, c) central nervous system (CNS) iron deposition, and d) immune status in subjects with relapsing-remitting multiple sclerosis (RRMS) RRMS via several MRI techniques.
Interventions
DRUGRebif
44 mcg tiw
Sponsors
EMD Serono
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male and female subjects, 18-65 years of age, inclusive, at the time of informed consent signature 2. RRMS diagnosed according to the McDonald criteria, treatment naïve or currently using any of the FDA-approved DMDs (excluding natalizumab (Tysabri®), mitoxantrone or Rebif®) 3. Have a disease duration of up to twenty years 4. Be willing and able to comply with the study procedures for the duration of the trial 5. Have given written informed consent and signed Health Insurance Portability and Accountability Act (HIPAA) Authorization before any study- related activities are carried out 6. Female subjects must not be either pregnant or breast-feeding and must lack childbearing potential, as defined by either: The following inclusion criteria must be fulfilled by the Healthy Control subjects: 1. Male and female subjects, 18-65 years of age, inclusive, at the time of informed consent signature 2. Be willing and able to comply with the study procedures for the duration of the trial 3. Have given written informed consent and signed Health Insurance Portability and Accountability Act (HIPAA) Authorization before any study- related activities are carried out 4. Female subjects must not be either pregnant or breast-feeding and must lack childbearing potential, as defined by either:
Exclusion criteria
1. Have received treatment within three months prior to Screening with interferon-beta-1a (Rebif®), IVIG or plasmapheresis 2. Have received treatment within thirty days prior to screening with immunosuppressant agents (e.g. including but not limited to mitoxantrone, cyclophosphamide, cladribine, fludarabine, cyclosporine or total body irradiation) or any other concomitant immunomodulatory therapies (e.g., azathioprine, methotrexate, CellCept®, natalizumab, alemtuzumab/Campath and other immunomodulators/monoclonal agents) 3. Have had a relapse within thirty days prior to the Screening Visit 4. Have received steroid treatment within thirty days prior to the initial MRI scan date at Study Day 1 5. Have inadequate liver function, defined by a alanine aminotransferase (ALT) \> 2.5x upper limit of normal (ULN), or alkaline phosphatase \> 2.5x ULN, or total bilirubin \> 1.5x ULN 6. Have inadequate bone marrow reserve, defined as a total white blood cell count \< 3.0x 109/L, platelet count \< 75x109/L, hemoglobin \< 100g/L 7. Have complete transverse myelitis or simultaneous-onset bilateral optic neuritis 8. Have a history of alcohol or drug abuse 9. Have thyroid dysfunction 10. Have moderate to severe renal impairment 11. Have a major medical or psychiatric illness that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the study protocol 12. Have a history of seizures not adequately controlled by treatment 13. Have serious or acute cardiac disease, such as uncontrolled dysrhythmias, uncontrolled angina pectoris, cardiomyopathy, or uncontrolled congestive heart failure 14. Have, in the opinion of the investigator, any visual, physical or cognitive impairment that would preclude the subject from complying with the study protocol 15. Have a known hypersensitivity or allergy to interferon-beta or any of the excipients 16. Have received an investigational drug or experimental procedure within the past thirty days 17. Are pregnant or attempting to conceive The following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Volume (in Millimeters Cubed) of Normal Appearing Brain Tissue (NABT) With Increasing (Indicative of Remyelination) Voxel-wise Magnetization Transfer Ratio (VW-MTR) From Baseline to 6 Months | Baseline to Month 6 | To characterize the effect of Rebif on remyelination using VW-MTR dynamic mapping of NABT in subjects ith RRMS over 6 months of treatment compared to a group of healthy Control (HC). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Volume (in Millimeters Cubed) of Normal Appearing Brain Tissue (NABT) With Decreasing (Indicative of Demyelination) Voxel-wise Magnetization Transfer Ratio (VW-MTR)From Baseline to 6 Months | Baseline to Month 6 | To characterize the effect of Rebif on demyelination using VW-MTR dynamic mapping of NABT in subjects ith RRMS over 6 months of treatment compared to a group of healthy Control (HC). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time to First Clinical Relapse | Months | Time to First Clinical Relapse |
| Clinical Relapses | Over 6 months | Clinical Relapses |
Countries
United States
Participant flow
Recruitment details
Recruitment took place at the clinic - June 16, 2010 through July 6, 2011
Pre-assignment details
Relapsing Remitting Multiple Sclerosis (RRMS)Participants could not have received treatment within 3 months prior to Screening with interferon-beta-1a (Rebif®), IVIG or plasmapheresis
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 RRMS Patients Rebif 44 mcg sc tiw | 23 |
| Arm 2 Healthy Control Healthy Control | 15 |
| Total | 38 |
Baseline characteristics
| Characteristic | Arm 2 Healthy Control | Arm 1 RRMS Patients | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 23 Participants | 38 Participants |
| Age, Continuous | 36.7 years STANDARD_DEVIATION 10.31 | 39.9 years STANDARD_DEVIATION 10.17 | 38.6 years STANDARD_DEVIATION 10.21 |
| Region of Enrollment United States | 15 participants | 23 participants | 38 participants |
| Sex: Female, Male Female | 8 Participants | 14 Participants | 22 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 23 | 8 / 15 |
| serious Total, serious adverse events | 2 / 23 | 0 / 15 |
Outcome results
Primary
Change in Volume (in Millimeters Cubed) of Normal Appearing Brain Tissue (NABT) With Increasing (Indicative of Remyelination) Voxel-wise Magnetization Transfer Ratio (VW-MTR) From Baseline to 6 Months
To characterize the effect of Rebif on remyelination using VW-MTR dynamic mapping of NABT in subjects ith RRMS over 6 months of treatment compared to a group of healthy Control (HC).
Time frame: Baseline to Month 6
Population: The analysis were run on the Intent-to-Treat (ITT) set defined as all RRMS subjects with at least one injection of Rebif and all HC who signed the informed consent form. Missing data were not imputed.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Arm 1 RRMS Patients | Change in Volume (in Millimeters Cubed) of Normal Appearing Brain Tissue (NABT) With Increasing (Indicative of Remyelination) Voxel-wise Magnetization Transfer Ratio (VW-MTR) From Baseline to 6 Months | 1206.1 mm^3 | Full Range 4081.621 |
| Arm 2 Healthy Control | Change in Volume (in Millimeters Cubed) of Normal Appearing Brain Tissue (NABT) With Increasing (Indicative of Remyelination) Voxel-wise Magnetization Transfer Ratio (VW-MTR) From Baseline to 6 Months | 342 mm^3 | Full Range 291.89 |
p-value: 0.061Wilcoxon (Mann-Whitney)
Secondary
Change in Volume (in Millimeters Cubed) of Normal Appearing Brain Tissue (NABT) With Decreasing (Indicative of Demyelination) Voxel-wise Magnetization Transfer Ratio (VW-MTR)From Baseline to 6 Months
To characterize the effect of Rebif on demyelination using VW-MTR dynamic mapping of NABT in subjects ith RRMS over 6 months of treatment compared to a group of healthy Control (HC).
Time frame: Baseline to Month 6
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Arm 1 RRMS Patients | Change in Volume (in Millimeters Cubed) of Normal Appearing Brain Tissue (NABT) With Decreasing (Indicative of Demyelination) Voxel-wise Magnetization Transfer Ratio (VW-MTR)From Baseline to 6 Months | 941.99 mm^3 | Full Range 1262.565 |
| Arm 2 Healthy Control | Change in Volume (in Millimeters Cubed) of Normal Appearing Brain Tissue (NABT) With Decreasing (Indicative of Demyelination) Voxel-wise Magnetization Transfer Ratio (VW-MTR)From Baseline to 6 Months | 297 mm^3 | Full Range 311.269 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Other Pre-specified
Clinical Relapses
Clinical Relapses
Time frame: Over 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 RRMS Patients | Clinical Relapses | 0.3 relapses per participant | Standard Deviation 0.88 |
Other Pre-specified
Time to First Clinical Relapse
Time to First Clinical Relapse
Time frame: Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 RRMS Patients | Time to First Clinical Relapse | 2.5 months | Standard Deviation 1.88 |