A Study to Investigate Efficacy, Safety, Pharmacodynamics and Pharmacokinetics of ASP6294 in the Treatment of Female Subjects With Bladder Pain Syndrome/Interstitial Cystitis

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.