Safety Study of Combination Therapy With Intramuscular Avonex and Oral Cellcept in Patients With Multiple Sclerosis

• ClinicalTrials.gov Identifier: NCT00223301
• Recruitment Status: Completed
• First Posted: September 22, 2005
• Last Update Posted: April 22, 2013
• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: Roche Pharma AG; Biogen
• Information provided by (Responsible Party): Elliot Frohman, University of Texas Southwestern Medical Center

Tracking Information

• First Submitted Date: September 19, 2005
• First Posted Date: September 22, 2005
• Last Update Posted Date: April 22, 2013
• Study Start Date: July 2004
• Actual Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 19, 2005): The primary objective of this safety/mechanistic study is to determine the safety and tolerability of oral Cellcept when used in combination with weekly intramuscular Avonex in early MS. Early MS for this study is defined at a definite diagnosis of less
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 12, 2006)

• To document changes in exacerbation frequency
• To document the incidence of mild, moderate, and severe exacerbations in the treated groups.
• To document changes in the level of sustained disability as measured by the expanded disability status score (EDSS) and ambulation index (AI) as assessed by the Kaplan-Meier methodology.
• To document changes in quality of life measures (MSQOL-54, SF-36, and Beck's Depression Index).
• To assess fatigue with the validated fatigue assessment inventory
• Neuroimmunological studies:At baseline, 6 and 12 months after treatment.
• Pharmacodynamics.
• Genetic Studies.

Original Secondary Outcome Measures (submitted: September 19, 2005)

• 1. To document changes in exacerbation frequency
• 2. To document the incidence of mild, moderate, and severe exacerbations in the treated groups.
• 3. To document changes in the level of sustained disability as measured by the expanded disability status score (EDSS) and ambulation index (AI) as assessed by the Kaplan-Meier methodology.
• 4. To document changes in quality of life measures (MSQOL-54, SF-36, and Beck's Depression Index).
• 5. To assess fatigue with the validated fatigue assessment inventory
• 6. Neuroimmunological studies:At baseline, 6 and 12 months after treatment.
• 7. Pharmacodynamics.
• 8. Genetic Studies.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety Study of Combination Therapy With Intramuscular Avonex and Oral Cellcept in Patients With Multiple Sclerosis
• Official Title: A One-Year Prospective, Randomized, Placebo-Controlled, Double-Blind, Phase II/III Safety Trial of Combination Therapy With IFN Beta-1a (Avonex) and Mycophenolate Mofetil (Cellcept) in Early Multiple Sclerosis

Brief Summary

1. To determine the safety and tolerability of oral Cellcept when used in combination with weekly intramuscular Avonex in early MS.
2. To document changes in exacerbation frequency,
3. To document the incidence of mild, moderate, and severe exacerbations in the treated groups (categorical analysis),
4. To document changes in the level of sustained disability as measured by the expanded disability status score (EDSS) and ambulation index (AI),
5. To document changes in quality of life measures,
6. To assess fatigue with the validated fatigue assessment inventory,
7. Neuroimmunological studies:At baseline, 6 and 12 months after treatment

Detailed Description

Design: Uni-center, double-blind, randomized, placebo-controlled study of Avonex + placebo vs Avonex + Cellcept

Rationale: A number of immunopathogenic mechanisms have been hypothesized to figure prominently in the processes that culminate in the characteristic plaque lesion. These include the role of cytokines, chemokines, excitatory amino acids, free radicals, superoxides, and nitric oxide synthetase products. Recognizing that the disease process in MS involves a cascade of biological events, sets the stage for strategically targeting specific immunopathogenetic steps through rational combination therapy regimens. We now propose a combination clinical trial utilizing Avonex and mycophenolate mofetil (MMF), a novel agent with a broad spectrum of anti- inflammatory mechanisms.

• Study population: MS patients who have been diagnosed with clinically definite, laboratory supported definite, or monosymptomatic MS meeting CHAMPS criteria ref , of either sex, who are between the ages of 21 and 50 inclusive.
• Treatment Groups: 12 patients in each group, ALL patients on Intramuscular Avonex. Cellcept/Placebo will be started at 250mg bid for one week and then escalated by 250mg bid until a target dose of 1000mg bid is achieved and Avonex 30 mcg IM q week

Patients also see an examining physician every three months, have brain MRI scans done every other month and donate WBCs through a procedure called leukapheresis (done every six months).

• Efficacy Parameters/Evaluations: EDSS, PSAT, MSFC and MRI, relapse rate and safety measures
• Safety Parameters/Evaluations: Safety will be assessed by virtue of changes in T2/FLAIR lesions (number and volume) and in gadolinium enhancements (measured at 6 and 12 months after treatment initiation) compared to baseline measurements derived from one pretreatment run- in scan. In addition, a variety of clinical assessments will be performed for the period of 12 months of treatment. We will enroll 12 patients in each group (24 total)

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Double; Primary Purpose: Treatment
• Condition: Multiple Sclerosis
• Intervention: Drug: Mycophenolate Mofetil (cellcept)
• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Enrollment (submitted: September 19, 2005): 24
• Original Enrollment: Same as current
• Actual Study Completion Date: March 2007
• Actual Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Between the ages of 21-45 inclusive
2. Clinically definite, laboratory supported definite relapsing MS of less than or equal to two years in duration or monosymptomatic MS meeting CHAMPS criteria ref .
3. At least one exacerbation in the preceding two years
4. Written informed consent.

Exclusion Criteria:

1. Primary progressive, secondary progressive or progressive relapsing MS.
2. Corticosteroids during the 60 days prior to study entry.
3. Treatment with plasma exchange within 90 days of preenrollment.
4. No prior exposure to total lymphoid irradiation.
5. No prior use of interferons, monoclonal antibodies, glatiramer acetate, methotrexate or other immunomodulatory drugs
6. A clinical relapse within 60 days prior to enrollment.
7. Pregnant/breastfeeding.
8. Patients with major medical illnesses.
9. Cognitive impairment interfering with ability to comply with the protocol.
10. Patients who need to remain on any contraindicated medication.
11. Diabetic
12. Inability to undergo MRI scan
13. On intravenous immunoglobulin protocol
14. HIV+ or RPR+
15. Females of childbearing age who have not undergone a sterilization procedure must be willing to practice effective birth control.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00223301
• Other Study ID Numbers: 1103-716
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Elliot Frohman, University of Texas Southwestern Medical Center
• Study Sponsor: University of Texas Southwestern Medical Center

Collaborators

• Roche Pharma AG
• Biogen

Investigators

• Principal Investigator: Elliot Frohman, MD/PhD; UT Southwestern Medical Center

• PRS Account: University of Texas Southwestern Medical Center
• Verification Date: April 2013