A Study to Test if Fremanezumab Reduces Pain in Patients With Interstitial Cystitis-Bladder Pain Syndrome

A Multicenter, Open-label Pilot Study of the Efficacy and Safety of Fremanezumab for Treatment of Female Patients With Interstitial Cystitis-Bladder Pain Syndrome

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.

Study Overview

• Status: Withdrawn
• Conditions: Interstitial Cystitis
• Intervention / Treatment: Drug: fremanezumab

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: fremanezumab; Two doses, each dose consists of 4 injections with prefilled syringes	Drug: fremanezumab; Two doses, each dose consists of 4 injections with prefilled syringes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Baseline to weeks 4 and 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Baseline, Week 4, and 8
Change from baselines in frequency of voids over the past 24 hours and change in average void volume.		Baseline, Week 4, and 8
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	Week 4 and 8
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)	Baseline, Week 4, and 8
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).	Baseline, Week 4, and 8
percent of patients who do not complete treatment due to all causes		8 weeks
number of adverse events during the study		8 Weeks
Incidence of abnormal clinical laboratory test results (serum chemistry)		Baseline - Week 8
Incidence of abnormal hematology laboratory test results		Baseline - Week 8
Incidence of abnormal coagulation laboratory test results.		Baseline - Week 8
Incidence of abnormal urinalysis laboratory test results.		Baseline - Week 8
Incidence of abnormal vital signs		Baseline - Week 8
clinically significant changes in physical examination	including body weight	Baseline - Week 8
Incidence of abnormal standard 12-lead electrocardiogram (ECG) findings		Baseline - Week 8
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.	Week 1 and Week 4
number of hypersensitivity/anaphylaxis reactions		Baseline - Week 8
percent of patients who do not complete the treatment due to adverse events		Baseline - Week 8
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	Baseline - Week 8
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.	Baseline - Week 8

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 15, 2020
• Primary Completion (Anticipated): February 10, 2022
• Study Completion (Anticipated): February 10, 2022

Study Registration Dates

• First Submitted: June 10, 2020
• First Submitted That Met QC Criteria: June 23, 2020
• First Posted (Actual): June 25, 2020

Study Record Updates

• Last Update Posted (Actual): November 9, 2021
• Last Update Submitted That Met QC Criteria: November 5, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Interstitial cystitis-bladder pain syndrome (IC-BPS)
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Cystitis; Cystitis, Interstitial
• Other Study ID Numbers: TV48125-CNS-20022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No