Clinical trial NCT03282318: A Study to Investigate Efficacy, Safety, Pharmacodynamics and Pharmacokinetics of ASP6294 in the Treatment of Female Subjects With Bladder Pain Syndrome/Interstitial Cystitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Pain Syndrome
Interstitial Cystitis
Keywords: Bladder Pain Syndrome
Interstitial Cystitis
ASP6294
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2017-09-13
Enrollment: 119
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change from Baseline in Average Mean Daily Pain (MDP) Score at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change from Baseline in Average Worst Daily Pain (WDP) Score at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Mean Voiding Frequency per 24 hours at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Mean Number of Level 3 or 4 Urgency Episodes (Based on Patient Perception of Intensity of Urgency Scale [PPIUS]) per 24 hours at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS) Total Score at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in BPIC-SS Worst Bladder Pain (Question 8) Score at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants With Moderately Improved or Better Grade on the Global Response Assessment (GRA) at Week 12
timeFrame: Week 12
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Site BE32001
city: Plzen
country: Czechia
facility: Site CZ42002
city: Duisburg
country: Germany
facility: Site DE49003
city: Duisburg
country: Germany
facility: Site DE49007
city: Holzminden
country: Germany
facility: Site DE49001
city: Markkleeberg
country: Germany
facility: Site DE49005
city: Budapest
country: Hungary
facility: Site HU36002
city: Csongrad
country: Hungary
facility: Site HU36001
city: Daugavpils
country: Latvia
facility: Site LV37103
city: Riga
country: Latvia
facility: Site LV37101
city: Riga
country: Latvia
facility: Site LV37102
city: Riga
country: Latvia
facility: Site LV37105
city: Sneek
country: Netherlands
facility: Site NL31007
city: Lodz
country: Poland
facility: Site PL48009
city: Szczecin
country: Poland
facility: Site PL48002
city: Warszawa
country: Poland
facility: Site PL48010
city: Wroclaw
country: Poland
facility: Site PL48007
city: St. Petersburg
country: Russian Federation
facility: Site RU70001
city: St. Petersburg
country: Russian Federation
facility: Site RU70002
city: St. Petersburg
country: Russian Federation
facility: Site RU70003
city: St. Petersburg
country: Russian Federation
facility: Site RU70006
city: St. Petersburg
country: Russian Federation
facility: Site RU70008
city: Barcelona
country: Spain
facility: Site ES34001
city: Madrid
country: Spain
facility: Site ES34008
city: Malaga
country: Spain
facility: Site ES34002
city: Valencia
country: Spain
facility: Site ES34007
city: Manchester
country: United Kingdom
facility: Site GB44002
city: Plymouth
country: United Kingdom
facility: Site GB44006
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Project Physician
role: STUDY_DIRECTOR
References:
citation: Imamura M, Scott NW, Wallace SA, Ogah JA, Ford AA, Dubos YA, Brazzelli M. Interventions for treating people with symptoms of bladder pain syndrome: a network meta-analysis. Cochrane Database Syst Rev. 2020 Jul 30;7(7):CD013325. doi: 10.1002/14651858.CD013325.pub2.