Clinical trial NCT01624714: Study of Alemtuzumab in Treatment Refractory MS Subjects/Alemtuzumab Naive & Alemtuzumab Experienced Subjects
Official title: Phase I Trial Monitoring Efficacy and Safety in Treatment of Alemtuzumab Naive Subjects and Data Collecting and Monitoring of Alemtuzumab Experienced Subjects With Refractory Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Multiple Sclerosis
Keywords: Treatment Refractory
Lead sponsor: Advanced Neurosciences Institute
Sponsor class: OTHER
First posted: 2012-06-21
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to treat prospectively documented clinic patients with treatment-refractory multiple sclerosis that are naïve to alemtuzumab. Alemtuzumab shows efficacy and rate of serious adverse events (SAEs) which is equivalent or better than standard of care treatment strategies used previously for treatment-refractory multiple sclerosis.

Detailed description: Hypothesis Alemtuzumab manifests efficacy (e.g. improved MS Severity score, and treatment stability in relapse rate and Expanded Disability Status Scale \[EDSS\] progression) and serious adverse events (SAEs) equivalent or better than standard of care treatment strategies used prior to treatment for treatment-refractory multiple sclerosis.

Objectives Treat prospectively documented clinic patients treatment-refractory multiple sclerosis that are naïve to alemtuzumab.

Obtain retrospective disability, relapse, and adverse events in alemtuzumab-experienced subjects previously treated outside of clinical trial settings for treatment-refractory MS.

Obtain prospective safety and efficacy data for multiple sclerosis symptoms, disability, and adverse effects following the use of alemtuzumab for treatment-refractory MS in a population with exposures to prior cytotoxic and monoclonal antibody therapy.

Transition alemtuzumab-experienced clinic patients into a clinical trial setting for additional treatment with alemtuzumab as needed for refractory MS.

Coprimary outcomes will be: change in EDSS and converted EDSS to MS Severity scale.

Secondary outcomes: changes in annualized relapse rate, days of high dose corticosteroids, MRI-based cerebral volumes and burden of disease (in selected subjects), serious adverse events, and corticosteroid use. A questionnaire will be used to assess patient satisfaction with alemtuzumab as compared to prior therapies.

Safety outcomes will be assessed and tabulated.

Eligibility criteria: Inclusion Criteria:

* This trial treats subjects with relapsing variants of MS, including relapsing-remitting, progressive-relapsing, transitional, or secondary progressive MS, not amenable to other aggressive therapy, prior relapses, EDSS 2.5-7.0 inclusive. Most will have generally moderate to severe disability at EDSS \>3 (EDSS 2.5-3 if significant cognitive complaints or MRI activity). Alemtuzumab experienced subjects at any EDSS level previously treated with alemtuzumab outside of a clinical trial are also eligible.

Inclusion Criteria for Alemtuzumab Experienced Subjects:

* All clinic patients who have been treated with alemtuzumab with our clinic method will be offered participation in the study, and may leave the study if desired after collection of data. Subjects wishing to sign informed consent but who have moved out of the region and are unable to be seen personally may be interviewed by telephone and included in the database after signing informed consent.

Exclusion Criteria:

* Subjects are excluded if they have purely slowly progressive or definite primary progressive MS (e.g. slowly progressive corticosteroid unresponsive myelopathy) with no documented recent relapses, advanced age (over 75 years), legal minor status, or a recognized contraindication to alemtuzumab (active infection, malignancy (other than considered surgical cures by oncologist or basal cell carcinoma), uncontrolled bleeding disorder, planned pregnancy in immediate future or unwillingness to use contraception, or if they are in another alemtuzumab clinical trial.
* Prior autoimmunity which is in remission or controlled will be considered at the investigator's discretion.
* Our clinic experience is that prior Grave's disease is not a contraindication to alemtuzumab therapy.
* We have not previously excluded patients from alemtuzumab on the basis of any humoral immune marker (e.g. anti-thyroid), and therefore do not plan to perform such testing in screening.

Primary outcomes:
measure: Change in Neurostatus Expanded Disability Status Scale
timeFrame: Baseline and every 6 months over 5 years
measure: Change in MS Severity Scale
timeFrame: Baseline and every 6 months for 5 years
Secondary outcomes:
measure: Change in annualized relapse rate
timeFrame: Every 6 months during study
measure: Number of treatment days with high dose corticosteroids
timeFrame: Every 6 months during study
measure: Rate of serious adverse events
timeFrame: Duration of study
measure: MRI-based cerebral volumes and burden of disease (in selected subjects)
timeFrame: Baseline and yearly X 5 years
Other outcomes:
Locations:
city: Franklin
country: United States
facility: Advanced Neurosciences Institute
state: Tennessee
Study officials:
affiliation: Advanced Neurosciences Institute (ANI)
name: Samuel F Hunter, MD
role: PRINCIPAL_INVESTIGATOR
References: