Alemtuzumab on Surrogate Markers of Disease Activity and Repair Using Advanced MRI Measures in Subjects With Relapsing Remitting Multiple Sclerosis

• Sponsor: University of Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT01395316
• Collaborator: Genzyme, a Sanofi Company (Industry)
• Enrollment: 8
• Arm: 1
• Duration (Months): 73

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Alemtuzumab	Phase 4

Detailed Description

To identify specific changes in T cell subsets and functions in Relapsing Remitting Multiple Sclerosis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Alemtuzumab on Surrogate Markers of Disease Activity and Repair Using Advanced MRI Measures in Subjects With Relapsing Remitting Multiple Sclerosis
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Jul 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alemtuzumab Single arm, single cohort study, all subjects will be dosed with alemtuzumab.	Drug: 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.; Other Names: CamPath MabPath

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• University of Chicago
• Genzyme, a Sanofi Company

Investigators

• Principal Investigator: Adil Javed, MD, University of Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT01395316
• Other Study ID Numbers: 10-490B
• First Posted: Jul 15, 2011
• Last Update Posted: Dec 7, 2018
• Last Verified: Nov 1, 2018

• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Alemtuzumab

Study Results

Participant Flow

Arm/Group Title	Alemtuzumab
Arm/Group Description	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.
Period Title: Overall Study
STARTED	8
COMPLETED	5
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Alemtuzumab
Arm/Group Description	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.
Overall Participants	8
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.6 (7.7)
Sex: Female, Male (Count of Participants)
Female	5 62.5%
Male	3 37.5%

Outcome Measures

1. Primary Outcome

Title	Diffusion and Myelin Fraction Water Changes on Magnetic Resonance Imaging (MRI)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alemtuzumab
Arm/Group Description	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.
Measure Participants	5
Mean (Standard Deviation) [percent Change]	-2.06 (0.01)

Adverse Events

Arm/Group Title	Alemtuzumab
Arm/Group Description	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.
All Cause Mortality
	Alemtuzumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Alemtuzumab
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Other (Not Including Serious) Adverse Events
	Alemtuzumab
	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)
Endocrine disorders
Hypothyroidism	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.