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Alternative Treatment Paradigm for Natalizumab Trial (ATP)

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ClinicalTrials.gov Identifier: NCT01710228
Recruitment Status : Withdrawn (sponsor stopped)
First Posted : October 19, 2012
Last Update Posted : December 29, 2016
Sponsor:
Collaborators:
Teva Pharmaceutical Industries
The University of Texas Health Science Center, Houston
University of Alabama at Birmingham
Charite University, Berlin, Germany
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center

Brief Summary:

This study is being done to determine the difference between natalizumab therapy followed by two different withdrawal strategies using Glatiramer Acetate (GA) treatment paradigms in preventing clinical relapses and other markers of disease activity in patients diagnosed with Multiple Sclerosis (MS).

We hypothesize that GA plus corticosteroids versus GA alone will prevent or reduce the re-occurrence of MS disease activity after discontinuation of natalizumab over a 12 month period. We further hypothesize that natalizumab therapy followed by GA treatment allows the reconstitution of the peripheral and CNS immune homeostasis.

Primary objective:

The primary endpoint will be the annualized relapse rate over the post randomization months as well as estimates of change over the natalizumab therapy period over the entire 12 months.

Secondary objectives:

To determine if and how long it takes for restoration of immune homeostasis under GA therapy following discontinuation of natalizumab.


Condition or disease Intervention/treatment Phase
Multiple Sclerosis (MS) Drug: methylprednisolone Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Alternative Treatment Paradigm for Natalizumab Trial
Study Start Date : July 2013
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2013


Arm Intervention/treatment
Placebo Comparator: Methylprednisolone placebo

subjects will be randomized 1:1 to receive either:

  1. Methylprednisolone placebo or
  2. Methylprednisolone
Drug: methylprednisolone
192 MG FOR 5 CONSECUTIVE DAYS EVERY 4 WEEKS FOR 10 MONTHS

Experimental: methylprednisolone

subjects will be randomized 1:1 to receive either:

  1. Methylprednisolone placebo or
  2. Methylprednisolone
Drug: methylprednisolone
192 MG FOR 5 CONSECUTIVE DAYS EVERY 4 WEEKS FOR 10 MONTHS




Primary Outcome Measures :
  1. annualized relapse rate [ Time Frame: 1 YEAR ]
    The primary endpoint will be the annualized relapse rate over the post randomization months as well as estimates of change over the natalizumab therapy period over the entire 12 months.


Secondary Outcome Measures :
  1. restoration of immune homeostasis - evaluated by regular brain MRI with contrast at baseline, month6 and month 12 of the study [ Time Frame: 1 YEAR ]
    To determine if and how long it takes for restoration of immune homeostasis under GA therapy following discontinuation of natalizumab. To determine if and how long it takes for restoration of immune homeostasis under GA therapy following discontinuation of natalizumab. The study will evaluate the cellular composition in peripheral blood in patients with relapsing forms of MS receiving natalizumab followed by GA therapy at 0, 3, 6, 9, and 12 months post treatment conversion. MP or PL will be added at month 3 and the impact of MP on restoration will be assessed by regular brain MRI imaging with contrast



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age between 18 and 60 years, inclusive.
  2. Diagnosis of relapsing forms of MS using revised McDonald Criteria 11.
  3. Patients who have not failed GA therapy.
  4. EDSS 0 - 5.5 (Functional system changes in cerebral (or mental) functions and in bowel and bladder functions not used in determining EDSS for protocol eligibility).
  5. No more than two relapses in the 12 months prior to initiating natalizumab therapy.
  6. A minimum of 9 doses of natalizumab prior to randomization.
  7. Disease controlled under natalizumab treatment demonstrated by the absence of relapses (no relapse in the 9 months prior to randomization)
  8. Understood and signed written informed consent, obtained prior to the study subject undergoing any study-related procedure, including screening tests.

Enrollment of patients in the TOUCHTM program at United States of America study sites as long as required: According to guidelines established by the Department of Health & Human Services, natalizumab is currently only available under a special restricted distribution program called TOUCHTM within the United States

Exclusion Criteria:

  1. Known hypersensitivity to GA.
  2. Initiation of new immunosuppressant treatment after the subject becomes protocol-eligible (except for corticosteroids) or enrollment in a concurrent trial unless an exception is granted following consideration by the MS Review Panel.
  3. Patients who were treated with GA before natalizumab therapy and failed GA therapy.
  4. Subjects with any history of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS).
  5. Active hepatitis B or hepatitis C infection or evidence of cirrhosis.
  6. HIV positivity.
  7. Uncontrolled diabetes mellitus defined as HbA1c > 8% and/or requiring intensive management.
  8. Uncontrolled viral, fungal, or bacterial infection (excluding asymptomatic bacteriuria).
  9. Any condition that, in the opinion of the investigators, would jeopardize the ability of the subject to tolerate treatment with GA.
  10. Prior history of malignancy, except localized basal cell or squamous skin cancer. Other malignancies for which the subject is judged to be cured by the administered therapy, such as head and neck cancer, or breast cancer, will be considered on an individual basis by the Study's MS review panel.
  11. Positive pregnancy test or inability or unwillingness to use effective means of birth control. Effective birth control is defined as:

    1. Refraining from all acts of vaginal intercourse (abstinence),
    2. Consistent use of birth control pills,
    3. Injectable birth control methods (®Depo-Provera, ®Norplant),
    4. Tubal sterilization or male partner who has undergone vasectomy,
    5. Placement of an IUD (intrauterine device)
    6. Use, with every act of intercourse, of a diaphragm with contraceptive jelly and/or condoms with contraceptive foam.
  12. Presence of metallic objects implanted in the body that would preclude the ability of the subject to safely have MRI exams.
  13. Psychiatric illness, mental deficiency, or cognitive dysfunction making compliance with treatment or informed consent impossible.

    -


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01710228


Locations
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United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Teva Pharmaceutical Industries
The University of Texas Health Science Center, Houston
University of Alabama at Birmingham
Charite University, Berlin, Germany
Investigators
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Principal Investigator: Olaf Stuve, MD PhD University of Texas Southwestern Medical Center

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Responsible Party: University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01710228     History of Changes
Other Study ID Numbers: STU092011-077
First Posted: October 19, 2012    Key Record Dates
Last Update Posted: December 29, 2016
Last Verified: December 2016
Keywords provided by University of Texas Southwestern Medical Center:
MS
Natalizumab
copaxone
Additional relevant MeSH terms:
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Multiple Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Natalizumab
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors