Study of Alemtuzumab in Treatment Refractory MS Subjects/Alemtuzumab Naive & Alemtuzumab Experienced Subjects

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Samuel Forrester Hunter, MD, PhD, Advanced Neurosciences Institute
ClinicalTrials.gov Identifier:
NCT01624714
First received: June 18, 2012
Last updated: March 8, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis
Drug: Alemtuzumab
Drug: Alemtuzumab immunotherapy
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Advanced Neurosciences Institute:

Primary Outcome Measures:
  • Change in Neurostatus Expanded Disability Status Scale [ Time Frame: Baseline and every 6 months over 5 years ] [ Designated as safety issue: Yes ]
  • Change in MS Severity Scale [ Time Frame: Baseline and every 6 months for 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change in annualized relapse rate [ Time Frame: Every 6 months during study ] [ Designated as safety issue: Yes ]
  • Number of treatment days with high dose corticosteroids [ Time Frame: Every 6 months during study ] [ Designated as safety issue: Yes ]
  • Rate of serious adverse events [ Time Frame: Duration of study ] [ Designated as safety issue: Yes ]
  • MRI-based cerebral volumes and burden of disease (in selected subjects) [ Time Frame: Baseline and yearly X 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: September 2012
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alemtuzumab Naive
Alemtuzumab Subjects (30) with prior treatment refractoriness and treatment experience EDSS 3.0-7.0 inclusive, without contraindications to alemtuzumab
Drug: Alemtuzumab
alemtuzumab 12 mg IV x 5 daily doses at baseline, alemtuzumab 12 mg IV x 3 daily doses at month 12
Other Names:
  • Campath
  • Lemtrada
Drug: Alemtuzumab immunotherapy
Alemtuzumab 60 mg over 5 days for first annual cycle, then 36 mg over 3 days for subsequent annual cycle, and as needed cycles in subsequent years.
Experimental: Alemtuzumab Experienced
Subjects with treatment refractory MS and prior alemtuzumab therapy (30)
Drug: Alemtuzumab
alemtuzumab 12 mg IV x 5 daily doses at baseline, alemtuzumab 12 mg IV x 3 daily doses at month 12
Other Names:
  • Campath
  • Lemtrada
Drug: Alemtuzumab immunotherapy
Alemtuzumab 60 mg over 5 days for first annual cycle, then 36 mg over 3 days for subsequent annual cycle, and as needed cycles in subsequent years.

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01624714

Locations
United States, Tennessee
Advanced Neurosciences Institute
Franklin, Tennessee, United States, 37064
Sponsors and Collaborators
Samuel Forrester Hunter, MD, PhD
Investigators
Principal Investigator: Samuel F Hunter, MD Advanced Neurosciences Institute (ANI)
  More Information

Additional Information:
No publications provided

Responsible Party: Samuel Forrester Hunter, MD, PhD, President, Advanced Neurosciences Institute
ClinicalTrials.gov Identifier: NCT01624714     History of Changes
Other Study ID Numbers: NPI-004
Study First Received: June 18, 2012
Last Updated: March 8, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration IND115794

Keywords provided by Advanced Neurosciences Institute:
Treatment Refractory

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Alemtuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014