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

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ClinicalTrials.gov Identifier: NCT03282318
Recruitment Status : Recruiting
First Posted : September 13, 2017
Last Update Posted : November 5, 2018
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )

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.

Condition or disease Intervention/treatment Phase
Bladder Pain Syndrome Interstitial Cystitis Drug: ASP6294 Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 163 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : September 28, 2017
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ASP6294
Participants will receive subcutaneous (SC) administrations of ASP6294 at weeks 0, 4 and 8.
Drug: ASP6294
Subcutaneous (SC) injection

Placebo Comparator: Placebo
Participants will receive SC administrations of Placebo at weeks 0, 4 and 8.
Drug: Placebo
SC injection




Primary Outcome Measures :
  1. Change from baseline in average mean daily pain (MDP) at Visit 6/Week 12 [ Time Frame: Baseline and Week 12 ]
    Participants will record participant's MDP each day in the evening into an e-diary. The MDP is the average pain experienced over the past 24 hours. MDP is measured using the 11-point numerical rating scale (NRS), (0-10) with 0 being no bladder pain and 10 being the worst possible pain.


Secondary Outcome Measures :
  1. Change from baseline in average worst daily pain (WDP) at Visit 6/Week 12 [ Time Frame: Baseline and Week 12 ]
    Participants will record participant's WDP each day in the evening into an e-diary. The WDP is the worst pain experienced over the past 24 hours. WDP is measured using the 11-point numerical rating scale (NRS), (0-10) with 0 being no bladder pain and 10 being the worst possible pain.

  2. Change from baseline in mean voiding frequency at Visit 6/Week 12 [ Time Frame: Baseline and Week 12 ]
    The mean voiding frequency is the mean of the recordings of voiding frequency in the 3 day electronic micturition diary in the week prior to the visit, with at least 2 days recorded in that week.

  3. Change from baseline in mean number of level 3 or 4 urgency episodes (using the PPIUS) per 24 hours as assessed with the 3 day electronic micturition diary within the week preceding the study visit, at Visit 6/Week 12 [ Time Frame: Baseline and Week 12 ]
    The patient perception of intensity of urgency scale (PPIUS) is a 5-point categorical scale and has a range from 0-4. 0 meaning "No urgency, I felt no need to empty my bladder, but did so for other reasons." and 4 meaning "Urge incontinence, I leaked before arriving to the toilet."

  4. Assessment of the Global Response Assessment (GRA) at Visit 6/Week 12 [ Time Frame: Up to Week 12 ]
    The GRA is self-reported and is a 7 grade GRA used to evaluate a participant's clinical condition relative to Baseline. The GRA reads: As compared to when the participant started the study, how would the participant rate the participant's overall symptoms now? The 7 GRA grades are "markedly worse", "moderately worse", "slightly worse", "no change", "slightly improved", "moderately improved" or "markedly improved". A successful GRA response is defined as the scores "moderately improved" or "markedly improved" disease.

  5. Change from baseline in Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS) at Visit 6/Week 12 [ Time Frame: Baseline and Week 12 ]
    The BPIC-SS is a psychometrically validated and reliable questionnaire with 8 questions concerning bladder pain over the previous 7 days. The BPIC-SS addresses urinary symptoms in 5 questions, all rated 0 - 4 (how often urinated because of pain, need to urinate just after previous urination, urination to avoid pain, pressure in the bladder and pain in the bladder), 2 questions address the impact of bladder pain (bothered by frequent urination during daytime and nighttime) and ends with a 0 - 10 NRS on worst pain over the last 7 days with 0 being no bladder pain and 10 being the worst possible pain. The total score will range from 0 to 38 with higher scores representing a worse situation, with a score of 19 or more indicating moderate/severe disease activity. Question 8 from the BPIC-SS is the question on worst bladder pain over the last 7 days on a 0-10 point NRS.

  6. Safety assessed by frequency, nature and severity of Adverse Events (AEs) [ Time Frame: Up to Week 18 ]
    An AE is considered "serious" if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, hospitalization, or medically important event.

  7. Number of participants with laboratory value abnormalities and/or AEs [ Time Frame: Up to Week 18 ]
    Number of participants with potentially clinically significant laboratory values.

  8. Number of participants with vital signs abnormalities and/or AEs [ Time Frame: Up to Week 18 ]
    Number of participants with potentially clinically significant vital sign values.

  9. Safety assessed by 12- lead electrocardiogram (ECG) [ Time Frame: Up to Week 18 ]
    ECGs will be recorded with the participant in the supine position, after the participant has been lying down for approximately 5 minutes. There should be at least 5 minutes between ECG measurements in case a repeat is needed. Any clinically significant adverse changes on the ECG will be reported as an AE.

  10. Safety assessed by sensory testing [ Time Frame: Up to Week 18 ]
    The sensory status will be assessed bilaterally on the participant's first toe, using 3 tests: the vibration test, the light touch test and the pin prick test.

  11. Number of participants with Physical Exam abnormalities and/or AEs/Serious Adverse Events (SAEs) [ Time Frame: Up to Week 18 ]
    Number of participants with potentially clinically significant physical exam values.

  12. Pharmacokinetics assessed by serum level of ASP6294 [ Time Frame: Up to Week 18 ]
    ASP6294 serum levels will be evaluated in blood samples collected.

  13. Pharmacodynamics assessed by serum level of total nerve growth factor (NGF) [ Time Frame: Up to Week 18 ]
    Total NGF serum levels will be evaluated in blood samples collected.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03282318


Contacts
Contact: Clinical Science +31 (0) 71 5455 050 astellas.registration@astellas.com

  Show 48 Study Locations
Sponsors and Collaborators
Astellas Pharma Europe B.V.
Investigators
Study Director: Project Physician Astellas Pharma Europe B.V.

Responsible Party: Astellas Pharma Europe B.V.
ClinicalTrials.gov Identifier: NCT03282318     History of Changes
Other Study ID Numbers: 6294-CL-0101
2016-004138-12 ( EudraCT Number )
First Posted: September 13, 2017    Key Record Dates
Last Update Posted: November 5, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Europe B.V. ):
Bladder Pain Syndrome
Interstitial Cystitis
ASP6294

Additional relevant MeSH terms:
Syndrome
Somatoform Disorders
Cystitis
Cystitis, Interstitial
Disease
Pathologic Processes
Mental Disorders
Urinary Bladder Diseases
Urologic Diseases