Multiple Sclerosis
Conditions
Brief summary
The MRI study is designed to identify possible mechanisms by which alemtuzumab acts to protect the brain from inflammation and how it may enhance repair through remyelination.
Detailed description
To identify specific changes in T cell subsets and functions in Relapsing Remitting Multiple Sclerosis.
Interventions
DRUGAlemtuzumab
10 mg/ml alemtuzumab intravenous infusion, sterile clear, colorless solution. dosage: 2 cycles. Month 0 dosed over 5 consecutive days: month 12 dosed over 3 consecutive days.
Sponsors
Genzyme, a Sanofi Company
University of Chicago
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1. Signed, informed consent form (ICF) 2. Age 18 to 50 years old (inclusive) as of signing the ICF 3. Diagnosis of MS per update of McDonald criteria, and cranial MRI scan demonstrating white matter lesions attributable to MS within 10 years of screening 4. Onset of MS symptoms (as determined by a neurologist) within 15 years of screening 5. EDSS score 0.0 to 5.0 (inclusive) 6. \>=2 MS attacks (first episode or relapse) occurring in the 24 months prior to screening, with \>=1 attack in the 12 months prior to screening, with objective neurological signs confirmed by a physician 7. Subjects previously enrolled and randomized to interferon beta 1a in the CARE-MS 323 and 324 studies, and who will be treated with Alemtuzumab through the CARE-MS extension study will be eligible to participate in the immunology and MRI studies of this protocol.
Exclusion criteria
1. Received prior therapy for MS other than corticosteroids within 28 days of screening; e.g., interferons, IV immunoglobulin, and glatiramer acetate 2. Exposure to natalizumab within 6 months of screening 3. Any prior exposure to mitoxantrone, mycophenolate mofetil, azathioprine, cladribine, cyclophosphamide, cyclosporine A, methotrexate, rituximab, or any other immunosuppressive agent other than systemic corticosteroid treatment 4. Has any progressive form of MS 5. History of malignancy (exception for basal cell skin carcinoma) 6. Previous hypersensitivity reaction to other immunoglobulin product 7. Intolerance of pulsed corticosteroids, especially a history of steroid psychosis 8. CD4+, CD8+, or CD19+ (i.e., absolute CD3+CD4+, CD3+CD8+, or CD19+/mm3) count \<LLN at Screening; if abnormal cell count(s) return to within normal limits, eligibility may be reassessed 9. Seropositivity for human immunodeficiency virus (HIV) 10. Significant autoimmune disease (e.g, immune cytopenias, rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders; vasculitis; inflammatory bowel disease; severe psoriasis) 11. Presence of anti-thyroid stimulating hormone (TSH) receptor (TSHR) antibodies 12. Active infection, e.g, deep-tissue infection, that the Investigator considers sufficiently serious to preclude study participation 13. Latent tuberculosis unless effective anti-tuberculosis therapy has been completed, or active tuberculosis. Patients will be assessed for this risk based on a screening questionnaire. 14. Infection with hepatitis B virus or hepatitis C virus 15. Of childbearing potential with a positive serum pregnancy test 16. Unwilling to agree to use a reliable and acceptable contraceptive method throughout the study period 17. Major psychiatric disorder that is not adequately controlled by treatment 18. Epileptic seizures that are not adequately controlled by treatment 19. Major systemic disease or other illness that would, in the opinion of the Investigator, compromise patient safety or interfere with the interpretation of study results 20. Medical, psychiatric, cognitive, or other conditions that, in the Investigator's opinion, compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study 21. Confirmed platelet count \< the lower limit of normal (LLN) of the evaluating laboratory at Screening or documented at \<100,000/uL within the past year on a sample without clumping 22. Prior history of invasive fungal infections 23. Cervical high risk human papillomavirus (HPV) positivity or abnormal cervical cytology other than abnormal squamous cells of undetermined significance (ASCUS). The patient may be eligible after the condition has been effectively treated (eg, follow-up HPV test is negative or cervical abnormality has been treated). 24. Seropositive for Trypanosoma cruzi or the Human T-lymphotropic virus type I or type II (HTLV-I/II) (testing required in endemic regions only) 25. Any other illness or infection (latent or active) that, in the Investigator's opinion, could be exacerbated by alemtuzumab treatment 26. Any hepatic or renal function value grade 2 or higher at Screening, with the exception of hyperbilirubinemia due to Gilbert's syndrome. See Table below, drawn from the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v3.0 (CTCAE), published 09 August 2006
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diffusion and Myelin Fraction Water Changes on Magnetic Resonance Imaging (MRI) | Baseline to Month 24 | Changes in normal appearing white matter from baseline through month 24. The MRI is designed to identify possible mechanisms by which alemtuzumab acts to protect the brain from inflammation and how it may enhance repair through remyelination. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alemtuzumab Single arm, single cohort study, all subjects will be dosed with alemtuzumab.
Alemtuzumab: 10 mg/ml alemtuzumab intravenous infusion, sterile clear, colorless solution. dosage: 2 cycles. Month 0 dosed over 5 consecutive days: month 12 dosed over 3 consecutive days. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | poor MRI quality | 1 |
Baseline characteristics
| Characteristic | Alemtuzumab |
|---|---|
| Age, Continuous | 32.6 years STANDARD_DEVIATION 7.7 |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Diffusion and Myelin Fraction Water Changes on Magnetic Resonance Imaging (MRI)
Changes in normal appearing white matter from baseline through month 24. The MRI is designed to identify possible mechanisms by which alemtuzumab acts to protect the brain from inflammation and how it may enhance repair through remyelination.
Time frame: Baseline to Month 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alemtuzumab | Diffusion and Myelin Fraction Water Changes on Magnetic Resonance Imaging (MRI) | -2.06 percent Change | Standard Deviation 0.01 |