Alternative Treatment Paradigm for Natalizumab Trial

NCT01710228 | Withdrawn Phase 2 DMC

• 1 other identifier: STU092011-077
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis (MS)

Keywords

MS; Natalizumab; copaxone

Outcome Measures

Primary Outcomes (1)

• annualized relapse rate

  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.

  1 YEAR

Secondary Outcomes (1)

• restoration of immune homeostasis - evaluated by regular brain MRI with contrast at baseline, month6 and month 12 of the study

  1 YEAR

Study Arms (2)

Methylprednisolone placebo

PLACEBO COMPARATOR

subjects will be randomized 1:1 to receive either: 1. Methylprednisolone placebo or 2. Methylprednisolone

Drug: methylprednisolone

methylprednisolone

EXPERIMENTAL

subjects will be randomized 1:1 to receive either: 1. Methylprednisolone placebo or 2. Methylprednisolone

Drug: methylprednisolone

Interventions

methylprednisolone DRUG

192 MG FOR 5 CONSECUTIVE DAYS EVERY 4 WEEKS FOR 10 MONTHS

Methylprednisolone placebo; methylprednisolone

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18 and 60 years, inclusive.
• Diagnosis of relapsing forms of MS using revised McDonald Criteria 11.
• Patients who have not failed GA therapy.
• 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).
• No more than two relapses in the 12 months prior to initiating natalizumab therapy.
• A minimum of 9 doses of natalizumab prior to randomization.
• Disease controlled under natalizumab treatment demonstrated by the absence of relapses (no relapse in the 9 months prior to randomization)
• 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

You may not qualify if:

• Known hypersensitivity to GA.
• 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.
• Patients who were treated with GA before natalizumab therapy and failed GA therapy.
• Subjects with any history of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS).
• Active hepatitis B or hepatitis C infection or evidence of cirrhosis.
• HIV positivity.
• Uncontrolled diabetes mellitus defined as HbA1c \> 8% and/or requiring intensive management.
• Uncontrolled viral, fungal, or bacterial infection (excluding asymptomatic bacteriuria).
• Any condition that, in the opinion of the investigators, would jeopardize the ability of the subject to tolerate treatment with GA.
• 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.
• Positive pregnancy test or inability or unwillingness to use effective means of birth control. Effective birth control is defined as:
• Refraining from all acts of vaginal intercourse (abstinence),
• Consistent use of birth control pills,
• Injectable birth control methods (®Depo-Provera, ®Norplant),
• Tubal sterilization or male partner who has undergone vasectomy,

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Teva Branded Pharmaceutical Products R&D, Inc.: collaborator
• The University of Texas Health Science Center, Houston: collaborator
• University of Alabama at Birmingham: collaborator
• Charite University, Berlin, Germany: collaborator

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Methylprednisolone

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Olaf Stuve, MD PhD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2012
• First Posted: October 19, 2012
• Study Start: July 1, 2013
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 29, 2016

Record last verified: 2016-12

Locations

US (1)