A Phase 2a, Randomized, Double-blind, Placebo-controlled, Parallel-group, Proof of Concept Study to Investigate Efficacy, Safety, Pharmacodynamics and Pharmacokinetics of ASP6294 in the Treatment of Female Subjects With Bladder Pain Syndrome/Interstitial Cystitis
A Phase 2a, Randomized, Double-blind, Placebo-controlled, Parallel-group, Proof of Concept Study to Investigate Efficacy, Safety, Pharmacodynamics and Pharmacokinetics of ASP6294 in the Treatment of Female Subjects With Bladder Pain Syndrome/Interstitial Cystitis
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.
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:
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 bladder pathology as specified below:
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.