Clinical trial NCT01085318: Rebif Advanced Magnetic Resonance Imaging (MRI) and Immunology Pilot Trial
Official title: A Twenty-four Week, Two Arm, Pilot Trial to Evaluate Remyelination/ Demyelination, Gray Matter Volume and Iron Deposition in the Central Nervous System (CNS) and Immune Status of Subjects With Relapsing-remitting Multiple Sclerosis (RRMS) Treated With Rebif® 44 mcg Subcutaneously (sc) Three Times a Week (Tiw) Compared to a Healthy Control Group
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Sclerosis
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
First posted: 2010-03-11
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


Eligibility criteria: 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 exclusion criteria must be fulfilled by the Healthy Control subjects:

1. Have met any of the above noted criteria

Primary outcomes:
measure: 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
timeFrame: Baseline to Month 6
Secondary outcomes:
measure: 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
timeFrame: Baseline to Month 6
Other outcomes:
measure: Clinical Relapses
timeFrame: Over 6 months
measure: Time to First Clinical Relapse
timeFrame: Months
Locations:
city: Rockland
country: United States
facility: EMD Serono, Inc.
state: Massachusetts
Study officials:
affiliation: EMD Serono
name: Fernando Dangond, MD
role: STUDY_DIRECTOR
References:
citation: Dwyer MG, Zivadinov R, Tao Y, Zhang X, Kennedy C, Bergsland N, Ramasamy DP, Durfee J, Hojnacki D, Weinstock-Guttman B, Hayward B, Dangond F, Markovic-Plese S. Immunological and short-term brain volume changes in relapsing forms of multiple sclerosis treated with interferon beta-1a subcutaneously three times weekly: an open-label two-arm trial. BMC Neurol. 2015 Nov 11;15:232. doi: 10.1186/s12883-015-0488-9.
citation: Zivadinov R, Dwyer MG, Markovic-Plese S, Kennedy C, Bergsland N, Ramasamy DP, Durfee J, Hojnacki D, Hayward B, Dangond F, Weinstock-Guttman B. Effect of treatment with interferon beta-1a on changes in voxel-wise magnetization transfer ratio in normal appearing brain tissue and lesions of patients with relapsing-remitting multiple sclerosis: a 24-week, controlled pilot study. PLoS One. 2014 Mar 13;9(3):e91098. doi: 10.1371/journal.pone.0091098. eCollection 2014.