A Study to Test if Fremanezumab Reduces Pain in Patients With Interstitial Cystitis-Bladder Pain Syndrome
Primary Purpose
Interstitial Cystitis
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
fremanezumab
Sponsored by
About this trial
This is an interventional treatment trial for Interstitial Cystitis focused on measuring Interstitial cystitis-bladder pain syndrome (IC-BPS)
Eligibility Criteria
Inclusion Criteria:
- has a diagnosis of IC-BPS according to the American Urological Association endorsed criteria for a duration of ≥6 months to ≤15 years
- has IC-BPS with moderate to severe bladder pain and urinary frequency
- has urinary frequency of ≥8 voids/day
- has had a cystoscopy within 6months before screening with report indicating absence of Hunner lesion(s). A patient who has not had a cystoscopy within 6months may undergo cystoscopy, at the physician's discretion, and be rescreened for study entry.
- has persistent symptoms despite an adequate trial of 3 months of dietary counseling and modification
- has a body mass index within 18.5 to 39 kg/m2 and a body weight ≥99 lbs.
- has non-pharmacologic interventions (such as physical therapy, pelvic floor massage, acupuncture, naturopathy, new initiation of mindfulness exercises, or cognitive behavioral therapy) that are unchanged for a minimum of 30 days before the screening visit
if of childbearing potential, must meet any of the following criteria:
- Patients must use 1 form of highly effective contraception with their partners during the entire study period and for 5 months after the last dose of the IMP
- Sexual abstinence is only considered a highly effective method if defined as refraining from heterosexual intercourse in the defined period. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a study, and withdrawal are not acceptable methods of contraception.
- Patients of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-HCG) pregnancy test at the screening visit (confirmed by urine dipstick β-HCG pregnancy test at baseline)
NOTE- Additional criteria apply; please contact the investigator for more information
Exclusion Criteria:
- has any of the following confounding conditions: bladder stones, lower ureteric stones, vaginal candidiasis for which treatment was completed less than 30 days before the screening visit, urethral diverticulum, incomplete bladder emptying, overactive bladder (ie, urinary urgency associated with urinary incontinence or fear of incontinence), radiation cystitis, tuberculosis cystitis, vaginitis, neurogenic bladder, or any other condition/disease which, in the opinion of the investigator, could compromise subject safety or confound the collection or interpretation of study results
is receiving any of the following treatments:
- intravesical therapy of any kind, corticosteroid therapy, cyclosporine, or anti-tumor necrosis factor-α inhibitors within 2 months before the screening visit (visit 1)
- cyclophosphamide or ketamine at any time
- mAbs targeting the CGRP pathway (including erenumab, eptinezumab, galcanezumab, or fremanezumab) at any time; if the subject has participated in a clinical study with any of these mAbs, it has to be confirmed that the subject received placebo in order to be eligible for this study
- has a known history of previous urinary diversion procedure with or without bladder removal or bladder augmentation
- has a known history of a cystoscopy with bladder biopsy, hydrodistention, or fulguration or triamcinolone injection ≤3 months before the screening visit
- was diagnosed with and/or treated for chronic migraine, defined as headaches occurring on ≥15 days/28-day period at any time over the past 3 months
- is receiving prophylactic treatment for migraine disorders
- has a known history of hypersensitivity reactions to injected proteins, including mAbs and animal venoms, or a history of Stevens-Johnson syndrome/toxic epidermal necrolysis syndrome
- has a lifetime known history of any psychotic and/or bipolar disorder
NOTE- Additional criteria apply; please contact the investigator for more information
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
fremanezumab
Arm Description
Two doses, each dose consists of 4 injections with prefilled syringes
Outcomes
Primary Outcome Measures
change from baseline in weekly average of the daily worst pain scores over the past 24 hours as measured on the PI-NRS
Pain Intensity-Numerical Rating Scale (PI-NRS) - An 11-point scale that measures pain from 0 to 10 (0=no pain; 10=worst possible pain)
Secondary Outcome Measures
change from baseline in the weekly average of the daily average pain PI-NRS score
The Pain Intensity-Numerical Rating Scale (PI-NRS) is an 11-point scale that measures pain from 0 to 10 (0=no pain; 10=worst possible pain)
Change from baselines in frequency of voids over the past 24 hours and change in average void volume.
Patient's Global Impression of Change (PGIC)
Improvement is recorded on a 7-point scale, with 1 indicating very much improved, 4 indicating no change, and 7 indicating very much worse
change from baseline in the BPIC-SS assessed over the most recent past 7 days
Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS) an 8-item questionnaire. Scores may range from 0 to 38 (0=no symptoms, 38=most severe symptoms)
change from baseline in the (GUPI) Questionnaire assessed over the most recent past 7 days
Genitourinary Pain Index (GUPI) Questionnaire. The GUPI has 10 pain items (total pain subscale score 0 to 23), 2 urinary symptom items (total urinary subscale score 0 to 10), and 3 QOL items (total QOL subscale score: 0 to 12).
percent of patients who do not complete treatment due to all causes
number of adverse events during the study
Incidence of abnormal clinical laboratory test results (serum chemistry)
Incidence of abnormal hematology laboratory test results
Incidence of abnormal coagulation laboratory test results.
Incidence of abnormal urinalysis laboratory test results.
Incidence of abnormal vital signs
clinically significant changes in physical examination
including body weight
Incidence of abnormal standard 12-lead electrocardiogram (ECG) findings
local tolerability at the injection site
Injection sites will be assessed for erythema, induration, ecchymosis, and pain immediately (ie, within 20 minutes ±5 minutes) and 1 hour (±15 minutes) after IMP administration.
number of hypersensitivity/anaphylaxis reactions
percent of patients who do not complete the treatment due to adverse events
anxiety and depression as measured by the HADS
Hospital Anxiety and Depression Scale (HADS): Scale for both anxiety and depression scored separately: 8-10 Mild, 11-14 Moderate, 15-21 Severe
suicidal ideation and behavior as measured by the C-SSRS
The Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Questions included the presence of the following: a wish to be dead; nonspecific active suicidal thoughts; actual suicide attempt; non-suicidal self-injurious behavior; interrupted attempt; aborted attempt; suicidal behavior; preparatory suicidal acts or behavior; and completed suicide.
The most severe type of ideation (i.e., 1-5 with 1 being the least severe and 5 being the most severe.
Full Information
NCT ID
NCT04447729
First Posted
June 10, 2020
Last Updated
November 5, 2021
Sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04447729
Brief Title
A Study to Test if Fremanezumab Reduces Pain in Patients With Interstitial Cystitis-Bladder Pain Syndrome
Official Title
A Multicenter, Open-label Pilot Study of the Efficacy and Safety of Fremanezumab for Treatment of Female Patients With Interstitial Cystitis-Bladder Pain Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Withdrawn due to logistic reasons
Study Start Date
October 15, 2020 (Anticipated)
Primary Completion Date
February 10, 2022 (Anticipated)
Study Completion Date
February 10, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective of the study is to evaluate the efficacy of fremanezumab in reducing pain in patients with interstitial cystitis-bladder pain syndrome (IC-BPS).
A secondary efficacy objective of the study is to evaluate the effect of fremanezumab on other efficacy measures, including pain, voiding frequency, urinary symptoms, and quality of life.
And another secondary objective of the study is to evaluate the safety and tolerability of fremanezumab administered subcutaneously in adult patients with IC-BPS.
The planned active study period is 8 weeks; the entire planned study duration for each patient is 13 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Interstitial Cystitis
Keywords
Interstitial cystitis-bladder pain syndrome (IC-BPS)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
fremanezumab
Arm Type
Experimental
Arm Description
Two doses, each dose consists of 4 injections with prefilled syringes
Intervention Type
Drug
Intervention Name(s)
fremanezumab
Intervention Description
Two doses, each dose consists of 4 injections with prefilled syringes
Primary Outcome Measure Information:
Title
change from baseline in weekly average of the daily worst pain scores over the past 24 hours as measured on the PI-NRS
Description
Pain Intensity-Numerical Rating Scale (PI-NRS) - An 11-point scale that measures pain from 0 to 10 (0=no pain; 10=worst possible pain)
Time Frame
Baseline to weeks 4 and 8
Secondary Outcome Measure Information:
Title
change from baseline in the weekly average of the daily average pain PI-NRS score
Description
The Pain Intensity-Numerical Rating Scale (PI-NRS) is an 11-point scale that measures pain from 0 to 10 (0=no pain; 10=worst possible pain)
Time Frame
Baseline, Week 4, and 8
Title
Change from baselines in frequency of voids over the past 24 hours and change in average void volume.
Time Frame
Baseline, Week 4, and 8
Title
Patient's Global Impression of Change (PGIC)
Description
Improvement is recorded on a 7-point scale, with 1 indicating very much improved, 4 indicating no change, and 7 indicating very much worse
Time Frame
Week 4 and 8
Title
change from baseline in the BPIC-SS assessed over the most recent past 7 days
Description
Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS) an 8-item questionnaire. Scores may range from 0 to 38 (0=no symptoms, 38=most severe symptoms)
Time Frame
Baseline, Week 4, and 8
Title
change from baseline in the (GUPI) Questionnaire assessed over the most recent past 7 days
Description
Genitourinary Pain Index (GUPI) Questionnaire. The GUPI has 10 pain items (total pain subscale score 0 to 23), 2 urinary symptom items (total urinary subscale score 0 to 10), and 3 QOL items (total QOL subscale score: 0 to 12).
Time Frame
Baseline, Week 4, and 8
Title
percent of patients who do not complete treatment due to all causes
Time Frame
8 weeks
Title
number of adverse events during the study
Time Frame
8 Weeks
Title
Incidence of abnormal clinical laboratory test results (serum chemistry)
Time Frame
Baseline - Week 8
Title
Incidence of abnormal hematology laboratory test results
Time Frame
Baseline - Week 8
Title
Incidence of abnormal coagulation laboratory test results.
Time Frame
Baseline - Week 8
Title
Incidence of abnormal urinalysis laboratory test results.
Time Frame
Baseline - Week 8
Title
Incidence of abnormal vital signs
Time Frame
Baseline - Week 8
Title
clinically significant changes in physical examination
Description
including body weight
Time Frame
Baseline - Week 8
Title
Incidence of abnormal standard 12-lead electrocardiogram (ECG) findings
Time Frame
Baseline - Week 8
Title
local tolerability at the injection site
Description
Injection sites will be assessed for erythema, induration, ecchymosis, and pain immediately (ie, within 20 minutes ±5 minutes) and 1 hour (±15 minutes) after IMP administration.
Time Frame
Week 1 and Week 4
Title
number of hypersensitivity/anaphylaxis reactions
Time Frame
Baseline - Week 8
Title
percent of patients who do not complete the treatment due to adverse events
Time Frame
Baseline - Week 8
Title
anxiety and depression as measured by the HADS
Description
Hospital Anxiety and Depression Scale (HADS): Scale for both anxiety and depression scored separately: 8-10 Mild, 11-14 Moderate, 15-21 Severe
Time Frame
Baseline - Week 8
Title
suicidal ideation and behavior as measured by the C-SSRS
Description
The Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Questions included the presence of the following: a wish to be dead; nonspecific active suicidal thoughts; actual suicide attempt; non-suicidal self-injurious behavior; interrupted attempt; aborted attempt; suicidal behavior; preparatory suicidal acts or behavior; and completed suicide.
The most severe type of ideation (i.e., 1-5 with 1 being the least severe and 5 being the most severe.
Time Frame
Baseline - Week 8
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
has a diagnosis of IC-BPS according to the American Urological Association endorsed criteria for a duration of ≥6 months to ≤15 years
has IC-BPS with moderate to severe bladder pain and urinary frequency
has urinary frequency of ≥8 voids/day
has had a cystoscopy within 6months before screening with report indicating absence of Hunner lesion(s). A patient who has not had a cystoscopy within 6months may undergo cystoscopy, at the physician's discretion, and be rescreened for study entry.
has persistent symptoms despite an adequate trial of 3 months of dietary counseling and modification
has a body mass index within 18.5 to 39 kg/m2 and a body weight ≥99 lbs.
has non-pharmacologic interventions (such as physical therapy, pelvic floor massage, acupuncture, naturopathy, new initiation of mindfulness exercises, or cognitive behavioral therapy) that are unchanged for a minimum of 30 days before the screening visit
if of childbearing potential, must meet any of the following criteria:
Patients must use 1 form of highly effective contraception with their partners during the entire study period and for 5 months after the last dose of the IMP
Sexual abstinence is only considered a highly effective method if defined as refraining from heterosexual intercourse in the defined period. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a study, and withdrawal are not acceptable methods of contraception.
Patients of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-HCG) pregnancy test at the screening visit (confirmed by urine dipstick β-HCG pregnancy test at baseline)
NOTE- Additional criteria apply; please contact the investigator for more information
Exclusion Criteria:
has any of the following confounding conditions: bladder stones, lower ureteric stones, vaginal candidiasis for which treatment was completed less than 30 days before the screening visit, urethral diverticulum, incomplete bladder emptying, overactive bladder (ie, urinary urgency associated with urinary incontinence or fear of incontinence), radiation cystitis, tuberculosis cystitis, vaginitis, neurogenic bladder, or any other condition/disease which, in the opinion of the investigator, could compromise subject safety or confound the collection or interpretation of study results
is receiving any of the following treatments:
intravesical therapy of any kind, corticosteroid therapy, cyclosporine, or anti-tumor necrosis factor-α inhibitors within 2 months before the screening visit (visit 1)
cyclophosphamide or ketamine at any time
mAbs targeting the CGRP pathway (including erenumab, eptinezumab, galcanezumab, or fremanezumab) at any time; if the subject has participated in a clinical study with any of these mAbs, it has to be confirmed that the subject received placebo in order to be eligible for this study
has a known history of previous urinary diversion procedure with or without bladder removal or bladder augmentation
has a known history of a cystoscopy with bladder biopsy, hydrodistention, or fulguration or triamcinolone injection ≤3 months before the screening visit
was diagnosed with and/or treated for chronic migraine, defined as headaches occurring on ≥15 days/28-day period at any time over the past 3 months
is receiving prophylactic treatment for migraine disorders
has a known history of hypersensitivity reactions to injected proteins, including mAbs and animal venoms, or a history of Stevens-Johnson syndrome/toxic epidermal necrolysis syndrome
has a lifetime known history of any psychotic and/or bipolar disorder
NOTE- Additional criteria apply; please contact the investigator for more information
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Teva Medical Expert, MD
Organizational Affiliation
Teva Branded Pharmaceutical Products R&D, Inc.
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the study protocol and the statistical analysis plan. Requests will be reviewed for scientific merit, product approval status, and conflicts of interest. Patient level data will be de-identified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Please email USMedInfo@tevapharm.com to make your request.
Learn more about this trial
A Study to Test if Fremanezumab Reduces Pain in Patients With Interstitial Cystitis-Bladder Pain Syndrome
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