A Randomized Multicenter Double-Blind Clinical Trial to Evaluate the Efficacy and Safety of Mycophenolate Mofetil (CellCept) for the Treatment of Refractory Interstitial Cystitis (IC) (ICCRN RCT #2)

General Description

The ICCRN RCT2 study was a randomized, double-blind, placebo-controlled clinical trial that investigated the safety and effectiveness of the immunosuppressant CellCept (Mycophenolate Mofetil) in treating refractory interstitial cystitis (IC). Interstitial Cystitis (IC) is a bladder syndrome characterized as painful, debilitating and chronic, with no widely effective treatment. Characteristic symptoms include pain with bladder filling, and marked urinary frequency (to relieve pain). The presentation of symptoms can be quite variable among patients, suggesting that IC is a multi-factorial syndrome with several proposed etiologies, some of which may be interrelated. If the etiology of IC/PBS is in part due to an induced autoimmune/inflammatory disorder, immunosuppressant therapy is a reasonable consideration for a treatment trial.

Eligible participants were randomized to either CellCept or matching placebo in a 2:1 ratio. All subjects were treated and followed for a period of up to 16 weeks after randomization, including 12 weeks of study treatment and 4 weeks post-treatment. Participants completed the Global Response Assessment (GRA) following treatment. Laboratory values (complete blood counts, liver enzymes) and physical symptoms were closely monitored for adverse events at regular intervals throughout the study. The study was halted prematurely as a result of a combination of factors including a black box warning issued by the Food and Drug Administration, slow recruitment and a decreased efficacy of the drug compared to placebo (interim efficacy analysis requested by the Data and Safety Monitoring Board)
The results of this limited study did not confirm or refute the hypothesis that immunosuppressive therapy may be beneficial to at least a subgroup of patients with IC.

Objectives

The primary objective of the ICCRN RCT2 study was to evaluate the efficacy and safety of CellCept (mycophenolate mofetil) in treating patients with treatment refractory interstitial cystitis (IC). Secondary objectives included investigating the association between clinical subgroups, characterized by differences in baseline characteristics (such as presence of ulcers, duration of symptoms, significant co-morbid diseases, serological abnormalities) and efficacy of CellCept.

Outcome Measure

The primary efficacy outcome measure was a patient-reported Global Response Assessment (GRA) at 12 weeks. Secondary measures obtained at baseline and 12 weeks included a 24-hour voiding diary, ratings of pain and frequency on a 10-point scale, and responses to a series of validated symptom questionnaires.

Criteria

Participants over the age of 18 who fulfilled the following criteria were enrolled:

(a) persistent symptoms of both urinary frequency and pain rated at least 4 on a scale of 0 to 10,

(b) failure of at least 24 weeks of active treatment with a minimum of 3 standard forms of therapy or combination of therapies for IC/PBS,

(c) a cystoscopic diagnosis of IC/PBS in the past with the findings of glomerulations and/or ulcerations, and

(d) a screening cystoscopy within the 24 weeks prior to entry, to check for unevaluated pathology.

Additional exclusion criteria are documented in the study protocol.

Outcome

The study was halted prematurely after interim assessment and found that MMF demonstrated efficacy similar to placebo in treating symptoms of refractory IC. However, it noted that the results of the study did not confirm or refute the hypothesis that immunosuppressive therapy may be beneficial to at least a subgroup of patients with IC.