Please select the eligibility criteria that correspond to the clinical trial below.
Title: Pilot Study Evaluating the Efficacy of Certolizumab Pegol for Interstitial Cystitis
Brief Summary: A Randomized, Double-blind, Placebo Controlled Trial of Certolizumab Pegol in Women with Refractory Interstitial Cystitis/Bladder Pain Syndrome


Options:
A: 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.
B: Inclusion Criteria:

* Subject's signs, symptoms and diagnostic work-up are in accordance with the international society for the study of bladder pain syndrome (ESSIC) definition for bladder pain syndrome/interstitial cystitis (BPS/IC): pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by at least 1 other urinary symptom such as persistent urge to void or frequency, for at least 6 months in absence of urinary infection or other obvious pathology or identifiable causes. There is documented proof of the diagnosis BPS/IC that has been entered into the subject's records at least 2 months prior to Visit 1/Screening.
* Subject has a score of ≥ 4 and ≤ 9 for pain as assessed by scoring the average pain of the week preceding Visit 1/Screening, using an 11-point NRS (0-10).
* Subject has an estimated voiding frequency of ≥ 8 and ≤ 30 voids per 24 hours.
* Subject has a score of ≥ 7 on the interstitial cystitis symptom index (ICSI) questionnaire.
* Subject must either:

  * Be of nonchildbearing potential:
  * Postmenopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to screening, or
  * Documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy)
  * Or, if of childbearing potential,
  * Agree not to try to become pregnant during the study and for 5 half-lives (i.e., 70 days) after the final study drug administration at Visit 5/Week 8, and
  * Have a negative urine pregnancy test at Visit 1/Screening, and
  * If heterosexually active, agree to consistently use 1 form of highly effective birth control starting at screening and throughout the study period and for 5 half-lives (i.e., 70 days) after the final study drug administration at Visit 5/Week 8.
* Subject must agree not to breastfeed starting at screening and throughout the study period, and for 5 half-lives (i.e., 70 days) after the final study drug administration at Visit 5/Week 8.
* Subject must agree not to donate ova starting at screening and throughout the study period, and for 5 half-lives (i.e., 70 days) after the final study drug administration at Visit 5/Week 8.
* Subject must be willing and able to comply with study requirements (e.g., complete questionnaires and diaries, able to read and attend all required study visits).
* Subject agrees not to participate in another interventional study while participating in the present study (i.e., between Visit 1/Screening and Visit 7/Week 18).
* Subject has undergone at least 2 different therapies for BPS/IC with unsatisfactory results, prior to study entry.
* Subject has at least moderate pain as reflected by an average MDP of ≥ 4.0 and ≤ 9.0. The average MDP is the average of daily assessments of MDP in the week prior to the visit with at least 5 recordings. Additionally, the MDP recordings must not differ over 4 points between consecutive days.
* Subject has a mean voiding frequency of ≥ 8.0 and ≤ 30.0 per 24 hours as assessed with the 3 day electronic micturition diary in the week prior to the visit.
* Subject is confirmed to be willing to comply and has shown to be compliant with all study requirements during the run-in period.

Exclusion Criteria:

* Subject has osteoarthritis or has a history of rapidly progressive osteoarthritis.
* Subject has a score of ≥ 30 on the Pain Catastrophizing Scale (PCS).
* Subject has a score of \> 12 on the HADS-D (Hospital Anxiety and Depression Scale - Depression subscale).
* Subject has significant pelvic floor pain or spasm which is considered the main cause of the chronic pelvic/bladder pain as concluded by the investigator based on the pelvic floor examination.
* Subject has undergone a fulguration or excision of a Hunner's lesion any time prior to the screening visit.
* Subject has recently undergone or started treatment for BPS/IC as specified below:

  * subject has undergone a cystoscopy with hydrodistension or Botox injections in the bladder within 6 months prior to the screening visit.
  * subject has received non-pharmacological interventions for BPS/IC (including but not limited to electric stimulation therapy or acupuncture therapy) within 3 months prior to the screening visit.
  * subject has received any intravesical pharmacological treatment for BPS/IC (including but not limited to heparin or dimethyl sulfoxide) within 4 weeks prior to the screening visit
  * subject had an initiation, discontinuation, or variation in the dose and/or frequency of antimuscarinics, mirabegron, antidepressants (including amitriptyline), anticonvulsants, benzodiazepines, skeletal muscle relaxants, nonsteroidal anti-inflammatory drugs, non-opioid analgesics, pentosan polysulphate sodium, homeopathic medication and/or herbal therapies during the last 4 weeks prior to the screening visit.
  * subject has had changes in non-pharmacological treatment for BPS/IC (e.g., diet or physical therapy) during the last 4 weeks prior to the screening visit.
* Subject has bladder pathology as specified below:

  * a post-void residual (PVR) \>200 mL.
  * subject has a known currently symptomatic urethral diverticulum.
  * subject has genital tract condition or pelvic pathology (e.g., post-partum, post-pelvic surgery, post-hysterectomy) that may complicate diagnosis and the evaluation of pelvic pain and urinary symptoms. Note: A history of a Cesarean section is not a reason for exclusion.
  * subject has a known currently symptomatic bladder or ureteral calculi.
  * subject currently has cystitis (radiation cystitis, Bacillus Calmette-Guérin-induced cystitis, bacterial/tuberculous cystitis, cyclophosphamide cystitis) or has had a documented symptomatic bacterial cystitis within the last 1 month prior to the screening visit. In case of bacterial cystitis (UTI), the subject can be re-screened 1 month after successful treatment.
  * subject has currently clinically significant urinary bladder abnormalities (e.g., bladder mass, bladder stone, bladder diverticulum, small contracted end-stage bladder), except for abnormalities associated with BPS/IC.
  * subject has had any invasive procedures of either the urinary bladder, urethra, ureter or renal pelvis (e.g., transurethral resection of bladder \[including bladder biopsy\], urethral dilatation, endovesicular lithotripsy) within 3 months prior to the screening visit.
  * subject has a known current neurologic disease or a defect affecting urinary bladder function (e.g., neurogenic bladder, systemic or central neurological disease, such as Multiple Sclerosis or Parkinson's disease).
  * subject has a known current lower urinary tract malignancy. In case of positive sediment (micro) hematuria results, local procedures/guidelines will need to be followed to exclude malignancy. Only if hematuria has been present within the last 6 months and malignancy has been adequately ruled out by the investigator according to local diagnostic procedures, the subject does not have to be excluded. Note that if the subject had a (negative) bladder biopsy, the subject can only be re-screened after 3 months following this biopsy. Documentation of all diagnostic outcomes and investigator's decisions need to be available.
* Subject has a known history of, or currently has inflammatory bowel disease (i.e., Crohn's Disease or Ulcerative Colitis) and/or Sjögren Syndrome.
* Subject has a known current severe constipation and/or severe diarrhea, severe active diverticulitis and/or severe gastrointestinal bleeding.
* Subject has a known or suspected hypersensitivity to ASP6294 or any components of the formulation used.
* Subject has been pregnant within 6 months prior to screening assessment or breast feeding within 3 months prior to screening.
* Subject has a known history of an allergic or anaphylactic reaction to biological drugs (e.g., \[monoclonal\] antibodies including tanezumab or fusion proteins).
* Subject has received a biological drug (e.g. \[monoclonal\] antibodies including tanezumab or fusion proteins) during the last 6 months prior to the screening visit.
* Subject has a known history of hepatitis B or C or human immunodeficiency virus (HIV) infection.
* Subject has a known history of or has a currently active or treated sexually transmittable disease (including genital herpes).
* Subject has a known current substance abuse issue (including alcoholism).
* Subject has peripheral neuropathy, or an abnormality has been observed during the sensory testing at Visit 1/Screening.
* Subject has a known currently clinically severe, unstable or uncontrolled renal, hepatic, respiratory, hematological, genitourinary (except BPS/IC), cardiovascular, endocrine, neurological, psychiatric, or other medical illness that may put the subject at safety risk or may mask measures of efficacy.
* Subject has had any malignancy diagnosed within 5 years prior to the screening visit, except for curative treated localized non-melanoma skin cancer (e.g. basal cell or squamous cell carcinoma).
* Subject has a known current psychiatric condition, mental incapacity, language barrier or the inability to read that would impair the subject's successful participation in the study.
* Subject has a body mass index of ≥ 40 kg/m\^2 as sign of morbid obesity.
* Subject has any condition that makes the subject unsuitable for study participation.
* Subject has received investigational therapy (i.e., not yet approved experimental medicine) within 28 days or 5 half-lives, whichever is longer, prior to the screening visit.
* Subject is an employee of the Astellas Group, the Contract Research Organization (CRO) involved, or the investigator site executing the study.
* Results of the Visit 1/Screening blood sample indicate that the subject has active hepatic and/or biliary disease, defined as: liver enzymes aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2 times the upper limit of normal (ULN), or total bilirubin (TBL) \> 1.5 times the ULN.
* Result of the Visit 1/Screening serum pregnancy test is positive.
* Results of the Visit 1/Screening blood/urine samples indicate that the subject has clinically significant abnormal biochemistry, hematology or urinalysis safety laboratory values.
C: Inclusion Criteria:

* Be females, ≥18 and ≤75 years of age, who have consistently had symptoms of bladder pain in addition to urinary urgency and/or urinary frequency for more than 12 months
* Have had the diagnosis of interstitial cystitis for \> 6 months (pain for at least 12 months) but ≤15 years
* Have average daily pain score of at least 5 out of 10 on the 11-point Numerical Rating Scale \[NRS\] pain scale in the 9 days prior to baseline
* Have undergone a cystoscopy and have documented visible signs of bladder bleeding, lesions or glomerulation within the last 36 months prior to baseline.
* Subjects if of child bearing potential, must agree to avoid pregnancy and use medically acceptable method of contraception from screening visit and throughout the study.
* Must be capable of voiding independently

Exclusion Criteria:

* Pelvic floor pain (\>5 out of 10 on the 11-point NRS pain scale following a pelvic pain assessment)
* Have a body mass index \[BMI\] of \<18 kg/m2 or \>39 kg/m2
* Have had a urinary tract infection including bacterial cystitis within the past 30 days.
* Have greater than 1+ hematuria on dipstick test at screening from an unknown cause
* History of previous procedure(s) (augmentation cystoplasty, cystectomy, or cystolysis) that has affected bladder function
D: Inclusion Criteria:

* Male and female adults at least 18 years of age;
* Moderate to severe interstitial cystitis, with a mean pain intensity score above a pre-defined level.

Exclusion Criteria:

* Less than 6 months since onset of interstitial cystitis symptoms;
* History of recurrent urinary tract infections, or genitourinary cancer;
* History of hepatitis B, C or human immunodeficiency virus (HIV);
* Use of certain drugs given into the bladder up to 1 month prior to study entry.

Answer: A