The Safety, Tolerability and Efficacy of LP-10 in Subjects With Refractory Moderate to Severe Hemorrhagic Cystitis

A Multicenter, Dose-Ranging Trial Evaluating the Safety, Tolerability and Efficacy of LP-10 in Subjects With Refractory Moderate to Severe Hemorrhagic Cystitis

The purpose of this study is to assess the safety and tolerability of three doses of LP-10 (intravesical tacrolimus). Twelve subjects meeting the inclusion and exclusion criteria will be enrolled and treated in a prospective and multi-center trial with LP-10. The proposed trial will recruit 12 subjects in a dose-escalation trial where 4 subjects will be allocated into each one of three groups.

Study Overview

• Status: Completed
• Conditions: Hemorrhagic Cystitis
• Intervention / Treatment: Drug: LP-10

Detailed Description

This is a multi-center, dose-ranging study including male and female subjects with refractory moderate to severe hemorrhagic cystitis as determined by a physician. A total of up to 12 subjects are anticipated and will be enrolled in study sites in the United States. Enrollment is expected to be completed within one year of initiating the study. The proposed trial will recruit 12 subjects in a dose-escalation trial where 4 subjects will be allocated into each one of three groups.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Janet Okonski, BS; Phone Number: 412-894-1853; Email: janet.okonski@lipella.com
• Study Contact Backup: Name: Michele Gruber, BS; Phone Number: 412-894-1853; Email: michele.gruber@lipella.com

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • San Francisco, California, United States, 94122
      • University of California San Francisco
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Michigan
    • Troy, Michigan, United States, 48084
      • Michigan Institute of Urology
  • New York
    • Poughkeepsie, New York, United States, 12603
      • Premier Medical Group
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Health Network Research Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Males and females, at least 18 years

• History of sterile moderate to severe HC (Grade 2-4) for at least 3 months documented in the medical record with at least 1 episode of macroscopic hematuria with or without clot
• Previous use of medications and/or treatment(s) for HC without success
• Patients of child-bearing capability agree to use a reliable form of birth control (condoms and/or oral contraceptives) during the course of instillation therapy and for 1 week thereafter
• Willing and capable of understanding and complying with all requirements of the protocol, including proper completion of the 3 day Hemorrhagic Cystitis Diary (HC Diary) and self-administered questionnaires

Exclusion Criteria:

• History of interstitial cystitis/painful bladder syndrome
• HC due to infection (bacterial, viral or fungal)
• Vesicoureteral reflux disease based on cystogram within past 12 months
• Subject is currently or has previously participated in another therapeutic or device study within 3 months of screening and has not returned to baseline
• Pregnant or lactating
• History of bleeding diathesis or active bleeding peptic ulcer disease
• Life expectancy less than 12 months
• PSA > 10.0 ng/dl (measured within the last 3 months)
• Known allergy to liposomes and/or egg yolk and/or tacrolimus
• Urinary retention requiring daily catheterization
• Previous augmentation cystoplasty
• Subjects currently taking prescribed treatment for HC will be able to continue the treatment throughout the course of the study. If the patient cannot be maintained on a stable dose of the medication(s) throughout the treatment and follow-up period they will be excluded
• Subject with history of intravesical treatment(s) within 1 week prior to Study Visit 1
• Sacral and/or pudendal nerve neuromodulation device (Interstim) within the last 6 months. Subjects would not be excluded if they had Interstim greater than 6 months ago and is on a stable setting.
• Evidence of renal impairment (creatinine > two times the upper limit of normal at Visit 1), hepatic impairment (AST or ALT > three times the upper limit of normal at Visit 1), clinically significant cardiovascular, respiratory, or psychiatric diseases per investigator's judgment
• Post-void residual (PVR) urine volume of > 150 mL at screening
• The presence of any clinically significant systemic disease or condition that in the opinion of the investigator would make the patient unsuitable for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LP-10 2mg; LP-10 (intravesical tacrolimus), 2mg reconstituted in sterile water for injection, intravesical instillations, up to two instillations, instillations will occur greater than 3 days but less than 7 days apart as needed.	Drug: LP-10; Intravesical tacrolimus
Experimental: LP-10 4mg; LP-10 (intravesical tacrolimus), 4mg reconstituted in sterile water for injection, intravesical instillations, up to two instillations, instillations will occur greater than 3 days but less than 7 days apart as needed.	Drug: LP-10; Intravesical tacrolimus
Experimental: LP-10 8mg; LP-10 (intravesical tacrolimus), 8mg reconstituted in sterile water for injection, intravesical instillations, up to two instillations, instillations will occur greater than 3 days but less than 7 days apart as needed.	Drug: LP-10; Intravesical tacrolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Reported Mean episodes of visible blood	Pre-post changes in mean episodes of visible blood in urine (or blood clots) on 3-day bladder diaries at baseline and primary endpoint	At every patient visit, up to 2 weeks following initial treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine Dipstick Mean episodes of Visible Blood	Mean episodes of visible blood in urine (or blood clots) and urine dipstick for quantitative grading of microscopic hematuria on bladder diaries	At every patient visit, up to 2 weeks following initial treatment
Mean urine hemoglobin concentration	Mean urine hemoglobin concentration	At every patient visit, up to 2 weeks following initial treatment
Urine analysis with microscopy	Urine analysis with microscopy including red blood cells per high power field test	At every patient visit, up to 2 weeks following initial treatment
Whole blood Add to dictionary levels	Whole blood tacrolimus levels	At every patient visit, up to 2 weeks following initial treatment
Blood chemistry and liver function test	Blood chemistry and liver function test	At every patient visit, up to 2 weeks following initial treatment
Patient Reported Global Response Assessment Survey Score	Changes in Global Response Assessment (GRA)	At every patient visit, up to 2 weeks following initial treatment
Patient Reported Urinary frequency	Changes in urinary frequency and incontinence measured on diaries	At every patient visit, up to 2 weeks following initial treatment
Bladder Cystoscopy	Cystoscopic changes in bladder	At initial treatment and on final patient visit, up to 2 weeks following initial treatment
Patient Reported Health Related Quality of Life Survey Score	Changes in Health Related Quality of Life (HRQOL) scores	At every patient visit, up to 2 weeks following initial treatment
Post void residual urine volume	Post void residual urine volume	At every patient visit, up to 2 weeks following initial treatment
Patient Reported Pain and Urgency	Change in pain and urgency 10 cm visual analog scales (VAS)	At every patient visit, up to 2 weeks following initial treatment
Incidence of Treatment-Emergent Adverse Events	Safety data will be collected by ongoing monitoring of adverse events, during the entire duration of the study, including need for blood transfusion, bladder irrigation, emergency room visit, hospitalization, urinary catheterization, and/or surgery in addition to patient reporting of changes in urinary frequency, hematuria/ clots, incontinence, spasm or discomfort.	At every patient visit, up to 2 weeks following initial treatment

Collaborators and Investigators

• Sponsor: Lipella Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Actual): August 21, 2023
• Study Completion (Actual): September 29, 2023

Study Registration Dates

• First Submitted: April 17, 2017
• First Submitted That Met QC Criteria: April 21, 2017
• First Posted (Actual): April 26, 2017

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Cystitis
• Other Study ID Numbers: Safety and Efficacy of LP-10

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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