Clinical Trial Result Information

Protocol number
WX18411

Title of Study
An optional continuation of double-blind treatment for patients who have achieved good symptom control with stable prednisone dosing and who have completed Protocol WX17798 (a prospective, randomized, double-blind, placebo-controlled, parallel group, multicenter, 36-week trial to assess the efficacy and safety of adjunct mycophenolate mofetil (MMF) to maintain or improve symptom control with reduced corticosteroids in patients with myasthenia gravis).

Sponsor
Hoffmann-La Roche

Company division
Pharmaceutical

Product name
CellCept

Generic name
mycophenolate mofetil

Therapeutic area
Myasthenia Gravis generalised

Clinical study summary
This study was a continuation of double-blind treatment with CellCept (mycophenolate mofetil) or placebo according to treatment assigned for Protocol WX17798. Visit 12 of Protocol WX17798 coincided with Visit 1 of this study. Patients returned at intervals for safety assessments, until withdrawal or database lock. During this continuation study, the dose of prednisone and cholinesterase inhibitors could be adjusted as clinically indicated.

Study center(s)
17 centers in France, Germany, Italy, Ukraine, UK and USA.

Phase of development
III

Objectives
To address investigator concerns about post-study treatment of patients who did well on double-blind treatment in Protocol WX17798 by providing the option to continue double-blind treatment until treatment assignment could be unblinded following database lock.

Methodology
Double-blind treatment was continued according to treatment assigned from Protocol WX17798, until the database for WX17798 was locked and unblinded. Patients returned at 8 week intervals for all safety assessments except hematology, until withdrawal or database lock. Hematology safety assessments were conducted at 4 week intervals until week 16, and every 8 weeks thereafter. Duration of individual treatment depended on the interval between completion of Protocol WX17798 and the unblinding of the treatment assignments.

Number of patients (planned/analyzed)
There were 38 randomized patients; 14 randomized to placebo and 24 randomized to CellCept.

Diagnosis and main criteria for inclusion
Diagnosis of myasthenia gravis.
Completed 36 weeks treatment with double-blind CellCept or placebo in Protocol WX17798.
Achieved good symptom control with a stable prednisone dose for the final four weeks of that study.

Test product, dose and mode of administration or test procedure
CellCept (mycophenolate mofetil) 1g po bid.

Duration of treatment
Unspecified - until withdrawal or database lock.

Reference therapy, dose and mode of administration or reference procedure
Placebo po bid

Criteria for evaluation (efficacy, safety)
Efficacy: No efficacy outcomes were measured.
Safety: Clinical laboratory tests, adverse events, physical examinations, vital signs and concomitant medications.

Statistical methods
All patients taking at least one dose of the trial medication and with a follow-up safety assessment were included in the safety analysis.

Summary (efficacy, safety, other results)
CellCept was generally well tolerated in this small study population of 24 CellCept patients and 14 placebo patients. No patients died in the continuation study. The overall incidence of AEs was higher in the placebo group (57.1%, 8 patients) compared with the CellCept group (45.8%, 11 patients). Generally, the increased incidence of infections and diarrhea in the CellCept group was the most noticeable difference between the two treatment groups and this is consistent with the established safety profile of CellCept. The CellCept group also received higher corticosteroid doses compared with the placebo group. Patients in the CellCept group who experienced infections also had a higher incidence of pre-existing medical conditions associated with an increased risk of infection. However, the incidence of treatment related infections in the CellCept group was low (8.3%, 2 patients), as was the incidence of severe infections reported as AEs (12.5%, 3 patients), and infections reported as SAEs (8.3%, 2 patients). The incidence of laboratory abnormalities was low in both treatment groups. No noticeable trends in laboratory abnormalities were seen in either treatment group. No clinically significant differences were observed between the treatment groups with regard to physical examinations, blood pressure, heart rate and ECG assessments.
It is difficult to draw any conclusions regarding the comparative safety data for the continuation study. The small number of patients entering the continuation study from the core study, the variation of treatment durations in the continuation study, and the entry of patients into the continuation study on the basis of their post-randomization safety experiences, amongst other factors, biases any inferences that could be made about long-term safety.
Overall however, the safety profile of CellCept in the Continuation Study WX18411 is broadly consistent with the Core Study WX17798 data, and the published data on CellCept. In particular, the rate of infections and diarrhea seen in this study appear to be consistent with the published data. The addition of CellCept to concomitant corticosteroid and anticholinesterase therapy did not result in any new safety concerns.

Conclusions
CellCept treatment was generally well tolerated in this small long-term safety study with exposure to CellCept up to 92 weeks. AEs that occurred with CellCept treatment in this study were consistent with the known safety profile of CellCept.

Date of report
9/10/2007

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