<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04447729</url>
  </required_header>
  <id_info>
    <org_study_id>TV48125-CNS-20022</org_study_id>
    <nct_id>NCT04447729</nct_id>
  </id_info>
  <brief_title>A Study to Test if Fremanezumab Reduces Pain in Patients With Interstitial Cystitis-Bladder Pain Syndrome</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Teva Branded Pharmaceutical Products R&amp;D, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Teva Branded Pharmaceutical Products R&amp;D, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of the study is to evaluate the efficacy of fremanezumab in reducing&#xD;
      pain in patients with interstitial cystitis-bladder pain syndrome (IC-BPS).&#xD;
&#xD;
      A secondary efficacy objective of the study is to evaluate the effect of fremanezumab on&#xD;
      other efficacy measures, including pain, voiding frequency, urinary symptoms, and quality of&#xD;
      life.&#xD;
&#xD;
      And another secondary objective of the study is to evaluate the safety and tolerability of&#xD;
      fremanezumab administered subcutaneously in adult patients with IC-BPS.&#xD;
&#xD;
      The planned active study period is 8 weeks; the entire planned study duration for each&#xD;
      patient is 13 weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Withdrawn due to logistic reasons&#xD;
  </why_stopped>
  <start_date type="Anticipated">October 15, 2020</start_date>
  <completion_date type="Anticipated">February 10, 2022</completion_date>
  <primary_completion_date type="Anticipated">February 10, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>change from baseline in weekly average of the daily worst pain scores over the past 24 hours as measured on the PI-NRS</measure>
    <time_frame>Baseline to weeks 4 and 8</time_frame>
    <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)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>change from baseline in the weekly average of the daily average pain PI-NRS score</measure>
    <time_frame>Baseline, Week 4, and 8</time_frame>
    <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)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baselines in frequency of voids over the past 24 hours and change in average void volume.</measure>
    <time_frame>Baseline, Week 4, and 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient's Global Impression of Change (PGIC)</measure>
    <time_frame>Week 4 and 8</time_frame>
    <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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change from baseline in the BPIC-SS assessed over the most recent past 7 days</measure>
    <time_frame>Baseline, Week 4, and 8</time_frame>
    <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)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change from baseline in the (GUPI) Questionnaire assessed over the most recent past 7 days</measure>
    <time_frame>Baseline, Week 4, and 8</time_frame>
    <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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>percent of patients who do not complete treatment due to all causes</measure>
    <time_frame>8 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>number of adverse events during the study</measure>
    <time_frame>8 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of abnormal clinical laboratory test results (serum chemistry)</measure>
    <time_frame>Baseline - Week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of abnormal hematology laboratory test results</measure>
    <time_frame>Baseline - Week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of abnormal coagulation laboratory test results.</measure>
    <time_frame>Baseline - Week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of abnormal urinalysis laboratory test results.</measure>
    <time_frame>Baseline - Week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of abnormal vital signs</measure>
    <time_frame>Baseline - Week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>clinically significant changes in physical examination</measure>
    <time_frame>Baseline - Week 8</time_frame>
    <description>including body weight</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of abnormal standard 12-lead electrocardiogram (ECG) findings</measure>
    <time_frame>Baseline - Week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>local tolerability at the injection site</measure>
    <time_frame>Week 1 and Week 4</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>number of hypersensitivity/anaphylaxis reactions</measure>
    <time_frame>Baseline - Week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>percent of patients who do not complete the treatment due to adverse events</measure>
    <time_frame>Baseline - Week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>anxiety and depression as measured by the HADS</measure>
    <time_frame>Baseline - Week 8</time_frame>
    <description>Hospital Anxiety and Depression Scale (HADS): Scale for both anxiety and depression scored separately: 8-10 Mild, 11-14 Moderate, 15-21 Severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>suicidal ideation and behavior as measured by the C-SSRS</measure>
    <time_frame>Baseline - Week 8</time_frame>
    <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.&#xD;
The most severe type of ideation (i.e., 1-5 with 1 being the least severe and 5 being the most severe.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Interstitial Cystitis</condition>
  <arm_group>
    <arm_group_label>fremanezumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two doses, each dose consists of 4 injections with prefilled syringes</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>fremanezumab</intervention_name>
    <description>Two doses, each dose consists of 4 injections with prefilled syringes</description>
    <arm_group_label>fremanezumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  has a diagnosis of IC-BPS according to the American Urological Association endorsed&#xD;
             criteria for a duration of ≥6 months to ≤15 years&#xD;
&#xD;
          -  has IC-BPS with moderate to severe bladder pain and urinary frequency&#xD;
&#xD;
          -  has urinary frequency of ≥8 voids/day&#xD;
&#xD;
          -  has had a cystoscopy within 6months before screening with report indicating absence of&#xD;
             Hunner lesion(s). A patient who has not had a cystoscopy within 6months may undergo&#xD;
             cystoscopy, at the physician's discretion, and be rescreened for study entry.&#xD;
&#xD;
          -  has persistent symptoms despite an adequate trial of 3 months of dietary counseling&#xD;
             and modification&#xD;
&#xD;
          -  has a body mass index within 18.5 to 39 kg/m2 and a body weight ≥99 lbs.&#xD;
&#xD;
          -  has non-pharmacologic interventions (such as physical therapy, pelvic floor massage,&#xD;
             acupuncture, naturopathy, new initiation of mindfulness exercises, or cognitive&#xD;
             behavioral therapy) that are unchanged for a minimum of 30 days before the screening&#xD;
             visit&#xD;
&#xD;
          -  if of childbearing potential, must meet any of the following criteria:&#xD;
&#xD;
               -  Patients must use 1 form of highly effective contraception with their partners&#xD;
                  during the entire study period and for 5 months after the last dose of the IMP&#xD;
&#xD;
               -  Sexual abstinence is only considered a highly effective method if defined as&#xD;
                  refraining from heterosexual intercourse in the defined period. The reliability&#xD;
                  of sexual abstinence needs to be evaluated in relation to the duration of the&#xD;
                  clinical study and the preferred and usual lifestyle of the patient. Periodic&#xD;
                  abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods),&#xD;
                  declaration of abstinence for the duration of a study, and withdrawal are not&#xD;
                  acceptable methods of contraception.&#xD;
&#xD;
               -  Patients of childbearing potential must have a negative serum beta-human&#xD;
                  chorionic gonadotropin (β-HCG) pregnancy test at the screening visit (confirmed&#xD;
                  by urine dipstick β-HCG pregnancy test at baseline)&#xD;
&#xD;
        NOTE- Additional criteria apply; please contact the investigator for more information&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  has any of the following confounding conditions: bladder stones, lower ureteric&#xD;
             stones, vaginal candidiasis for which treatment was completed less than 30 days before&#xD;
             the screening visit, urethral diverticulum, incomplete bladder emptying, overactive&#xD;
             bladder (ie, urinary urgency associated with urinary incontinence or fear of&#xD;
             incontinence), radiation cystitis, tuberculosis cystitis, vaginitis, neurogenic&#xD;
             bladder, or any other condition/disease which, in the opinion of the investigator,&#xD;
             could compromise subject safety or confound the collection or interpretation of study&#xD;
             results&#xD;
&#xD;
          -  is receiving any of the following treatments:&#xD;
&#xD;
               -  intravesical therapy of any kind, corticosteroid therapy, cyclosporine, or&#xD;
                  anti-tumor necrosis factor-α inhibitors within 2 months before the screening&#xD;
                  visit (visit 1)&#xD;
&#xD;
               -  cyclophosphamide or ketamine at any time&#xD;
&#xD;
               -  mAbs targeting the CGRP pathway (including erenumab, eptinezumab, galcanezumab,&#xD;
                  or fremanezumab) at any time; if the subject has participated in a clinical study&#xD;
                  with any of these mAbs, it has to be confirmed that the subject received placebo&#xD;
                  in order to be eligible for this study&#xD;
&#xD;
          -  has a known history of previous urinary diversion procedure with or without bladder&#xD;
             removal or bladder augmentation&#xD;
&#xD;
          -  has a known history of a cystoscopy with bladder biopsy, hydrodistention, or&#xD;
             fulguration or triamcinolone injection ≤3 months before the screening visit&#xD;
&#xD;
          -  was diagnosed with and/or treated for chronic migraine, defined as headaches occurring&#xD;
             on ≥15 days/28-day period at any time over the past 3 months&#xD;
&#xD;
          -  is receiving prophylactic treatment for migraine disorders&#xD;
&#xD;
          -  has a known history of hypersensitivity reactions to injected proteins, including mAbs&#xD;
             and animal venoms, or a history of Stevens-Johnson syndrome/toxic epidermal necrolysis&#xD;
             syndrome&#xD;
&#xD;
          -  has a lifetime known history of any psychotic and/or bipolar disorder&#xD;
&#xD;
        NOTE- Additional criteria apply; please contact the investigator for more information&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Teva Medical Expert, MD</last_name>
    <role>Study Director</role>
    <affiliation>Teva Branded Pharmaceutical Products R&amp;D, Inc.</affiliation>
  </overall_official>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>November 5, 2021</last_update_submitted>
  <last_update_submitted_qc>November 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Interstitial cystitis-bladder pain syndrome (IC-BPS)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystitis</mesh_term>
    <mesh_term>Cystitis, Interstitial</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_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.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04447729
org study id: TV48125-CNS-20022
nct id: NCT04447729
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: change from baseline in weekly average of the daily worst pain scores over the past 24 hours as measured on the PI-NRS
time frame: Baseline to weeks 4 and 8
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)
measure: change from baseline in the weekly average of the daily average pain PI-NRS score
time frame: Baseline, Week 4, and 8
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)
measure: 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
measure: Patient's Global Impression of Change (PGIC)
time frame: Week 4 and 8
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
measure: change from baseline in the BPIC-SS assessed over the most recent past 7 days
time frame: Baseline, Week 4, and 8
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)
measure: change from baseline in the (GUPI) Questionnaire assessed over the most recent past 7 days
time frame: Baseline, Week 4, and 8
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).
measure: percent of patients who do not complete treatment due to all causes
time frame: 8 weeks
measure: number of adverse events during the study
time frame: 8 Weeks
measure: Incidence of abnormal clinical laboratory test results (serum chemistry)
time frame: Baseline - Week 8
measure: Incidence of abnormal hematology laboratory test results
time frame: Baseline - Week 8
measure: Incidence of abnormal coagulation laboratory test results.
time frame: Baseline - Week 8
measure: Incidence of abnormal urinalysis laboratory test results.
time frame: Baseline - Week 8
measure: Incidence of abnormal vital signs
time frame: Baseline - Week 8
measure: clinically significant changes in physical examination
time frame: Baseline - Week 8
description: including body weight
measure: Incidence of abnormal standard 12-lead electrocardiogram (ECG) findings
time frame: Baseline - Week 8
measure: local tolerability at the injection site
time frame: Week 1 and Week 4
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.
measure: number of hypersensitivity/anaphylaxis reactions
time frame: Baseline - Week 8
measure: percent of patients who do not complete the treatment due to adverse events
time frame: Baseline - Week 8
measure: anxiety and depression as measured by the HADS
time frame: Baseline - Week 8
description: Hospital Anxiety and Depression Scale (HADS): Scale for both anxiety and depression scored separately: 8-10 Mild, 11-14 Moderate, 15-21 Severe
measure: suicidal ideation and behavior as measured by the C-SSRS
time frame: Baseline - Week 8
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.
arm group label: fremanezumab
arm group type: Experimental
description: Two doses, each dose consists of 4 injections with prefilled syringes
intervention type: Drug
intervention name: fremanezumab
description: Two doses, each dose consists of 4 injections with prefilled syringes
arm group label: fremanezumab
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Teva Medical Expert, MD
role: Study Director
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
responsible party type: Sponsor
mesh term: Cystitis
mesh term: Cystitis, Interstitial
sharing ipd: Yes
ipd 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.