a study to investigate efficacy, safety, pharmacodynamics and pharmacokinetics of asp6294 in the treatment of female subjects with bladder pain syndrome/interstitial cystitis

Conditions: Bladder Pain Syndrome; Interstitial Cystitis

Summary: the purpose of this study is to investigate efficacy, safety and tolerability of asp6294 in female participants with bladder pain syndrome/interstitial cystitis (bps/ic). this study will also investigate the pharmacokinetics (pk) and pharmacodynamics (pd) of asp6294 in female participants with bps/ic.


Eligibility criteria:
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.

Keywords: bladder pain syndrome interstitial cystitis asp6294