Pilot Study Evaluating the Efficacy of Certolizumab Pegol for Interstitial Cystitis

Interstitial cystitis (IC) is a chronic disabling bladder syndrome characterized by urinary
frequency, nocturia, urinary urgency, and pain or discomfort with bladder filling. There is
no cure for IC and the treatment options are suboptimal. Patients with IC report significant
negative effects on their physical and mental quality of life. The etiology of IC is unknown.
Certain aspects of IC suggest that autoimmunity may play a role in initiating or sustaining
the chronic inflammatory response. Bladder biopsies of patients with IC demonstrate an
increase number of mast cells. Mast cell activation with the release of tumor necrosis factor
(TNF) may mediate this bladder inflammation. Cimzia (certolizumab pegol) is a medication that
blocks the effect of TNF. Cimzia (certolizumab pegol) is FDA approved for the treatment of
rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and Crohn's disease. These
diseases are similar to IC. In this study, the hypothesis being tested is that Cimzia
(certolizumab pegol) will show efficacy in improving the symptoms of patients with IC.

Inclusion Criteria:

1. A diagnosis of IC/BPS defined based on AUA guidelines as the following: an unpleasant
sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder,
associated with lower urinary tract symptoms of more than 6 months duration, in the
absence of infection or identifiable causes, documented history or patient reported.

2. Only those patients with moderate to severe IC/BPS will be included in the study.

3. Able to provide informed consent to participate in the study and comply with study
requirements

4. Able to provide written authorization for use and release of health and research study
information

5. Written documentation of being provided California's Experimental Subject's Bill of
Rights

6. Females ≥18 and ≤ 65 years of age previously diagnosed with interstitial cystitis/
bladder pain syndrome (IC/BPS) for a duration of greater than 6 months

7. Female patients of child-bearing potential must have a negative serum pregnancy test
at Screening and use birth control while in the study.

8. O'Leary-Sant Interstitial Cystitis Symptom and Problem Indexes (OSPI) score ≥ 18

9. No history of any cancer.

10. No bacterial cystitis in previous 1 month

11. No active herpes in previous 3 months

12. Never treated with cyclophosphamide

13. No neurogenic bladder dysfunction (due to a spinal cord injury, stroke, Parkinson's
disease, multiple sclerosis, spina bifida or diabetic cystopathy)

14. Absence of bladder, ureteral or urethral calculi for previous 3 months

Exclusion criteria:

1. Symptoms are relieved at one month reevaluation visit after receiving IC/BPS behavior
modification advice at screening visit.

2. Symptoms are relieved by antimicrobials, antibiotics, or other medications for IC/BPS

3. Pregnant women, lactating mothers, nursing mothers, women suspected of being pregnant
and woman who plan to be pregnant during the course of the clinical trial

4. Males

5. Patients with inadequate renal, hepatic, or cardiac function

6. Patients with history of gross hematuria within 2 years.

7. Patients with the following medical history: Lower urinary tract anatomical anomaly,
pelvic radiotherapy, or active genital herpes

8. Patients with a history of tuberculosis (TB), recent exposure to TB, or recent travel
to TB endemic regions. Patients should have a recent negative PPD (or negative CXR)
prior to receiving treatment.

9. Patients who have undergone cystoscopy under anesthesia with bladder biopsy,
hydrodistension, or fulguration of Hunner's ulcer within 3 months

10. Patients taking the following treatments for interstitial cystitis at Screening:
Intravesical BCG, corticosteroid therapy, cyclosporine, or TNF-alpha inhibitors.

11. Patients with a history of receiving live vaccine including Flumist® influenza vaccine
in the past 3 months.

12. Patients with a history of allergic or anaphylactic reaction to a therapeutic or
diagnostic monoclonal antibody or IgG-fusion protein.

13. Patients with a history of alcohol, analgesic or drug abuse within 2 years of
Screening.

14. Patients with a history of any cancer.

15. Patients with a history of active Hepatitis B, Hepatitis C, or Human Immunodeficiency
Virus (HIV) infection, or who are known carriers (Hepatitis B).

16. Patients with a history of invasive fungal infections, recent travel to regions
endemic for the following invasive fungal infections: San Joaquin Fever,
aspergillosis, histoplasmosis, candidiasis, coccidiodomycosis, blastomycosis, and
pneumocystosis.

17. Patients with a history of diabetes mellitus.

18. Patients with a history of a neurologic disease included but not limited to central
demyelinating diseases, including multiple sclerosis; and a history of peripheral
demyelinating disease, including Guillain-Barre syndrome.

19. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or
investigational product administration or may interfere with the interpretation of
study results and, in the judgment of the Investigator, would make the patient
inappropriate for entry into this study.