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

Primary Purpose

Hemorrhagic Cystitis

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
LP-10
Sponsored by
Lipella Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemorrhagic Cystitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Arizona
  • University of California San Francisco
  • Emory University
  • Michigan Institute of Urology
  • Premier Medical Group
  • Temple University
  • Allegheny Health Network Research Institute
  • Vanderbilt University Medical Center
  • Baylor College of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

LP-10 2mg

LP-10 4mg

LP-10 8mg

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
Mean urine hemoglobin concentration
Mean urine hemoglobin concentration
Urine analysis with microscopy
Urine analysis with microscopy including red blood cells per high power field test
Whole blood Add to dictionary levels
Whole blood tacrolimus levels
Blood chemistry and liver function test
Blood chemistry and liver function test
Patient Reported Global Response Assessment Survey Score
Changes in Global Response Assessment (GRA)
Patient Reported Urinary frequency
Changes in urinary frequency and incontinence measured on diaries
Bladder Cystoscopy
Cystoscopic changes in bladder
Patient Reported Health Related Quality of Life Survey Score
Changes in Health Related Quality of Life (HRQOL) scores
Post void residual urine volume
Post void residual urine volume
Patient Reported Pain and Urgency
Change in pain and urgency 10 cm visual analog scales (VAS)
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.

Full Information

First Posted
April 17, 2017
Last Updated
January 9, 2023
Sponsor
Lipella Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03129126
Brief Title
The Safety, Tolerability and Efficacy of LP-10 in Subjects With Refractory Moderate to Severe Hemorrhagic Cystitis
Official Title
A Multicenter, Dose-Ranging Trial Evaluating the Safety, Tolerability and Efficacy of LP-10 in Subjects With Refractory Moderate to Severe Hemorrhagic Cystitis
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 1, 2020 (Actual)
Primary Completion Date
January 1, 2023 (Anticipated)
Study Completion Date
May 3, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lipella Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemorrhagic Cystitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Non-Randomized
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LP-10 2mg
Arm Type
Experimental
Arm Description
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.
Arm Title
LP-10 4mg
Arm Type
Experimental
Arm Description
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.
Arm Title
LP-10 8mg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
LP-10
Intervention Description
Intravesical tacrolimus
Primary Outcome Measure Information:
Title
Patient Reported Mean episodes of visible blood
Description
Pre-post changes in mean episodes of visible blood in urine (or blood clots) on 3-day bladder diaries at baseline and primary endpoint
Time Frame
At every patient visit, up to 2 weeks following initial treatment
Secondary Outcome Measure Information:
Title
Urine Dipstick Mean episodes of Visible Blood
Description
Mean episodes of visible blood in urine (or blood clots) and urine dipstick for quantitative grading of microscopic hematuria on bladder diaries
Time Frame
At every patient visit, up to 2 weeks following initial treatment
Title
Mean urine hemoglobin concentration
Description
Mean urine hemoglobin concentration
Time Frame
At every patient visit, up to 2 weeks following initial treatment
Title
Urine analysis with microscopy
Description
Urine analysis with microscopy including red blood cells per high power field test
Time Frame
At every patient visit, up to 2 weeks following initial treatment
Title
Whole blood Add to dictionary levels
Description
Whole blood tacrolimus levels
Time Frame
At every patient visit, up to 2 weeks following initial treatment
Title
Blood chemistry and liver function test
Description
Blood chemistry and liver function test
Time Frame
At every patient visit, up to 2 weeks following initial treatment
Title
Patient Reported Global Response Assessment Survey Score
Description
Changes in Global Response Assessment (GRA)
Time Frame
At every patient visit, up to 2 weeks following initial treatment
Title
Patient Reported Urinary frequency
Description
Changes in urinary frequency and incontinence measured on diaries
Time Frame
At every patient visit, up to 2 weeks following initial treatment
Title
Bladder Cystoscopy
Description
Cystoscopic changes in bladder
Time Frame
At initial treatment and on final patient visit, up to 2 weeks following initial treatment
Title
Patient Reported Health Related Quality of Life Survey Score
Description
Changes in Health Related Quality of Life (HRQOL) scores
Time Frame
At every patient visit, up to 2 weeks following initial treatment
Title
Post void residual urine volume
Description
Post void residual urine volume
Time Frame
At every patient visit, up to 2 weeks following initial treatment
Title
Patient Reported Pain and Urgency
Description
Change in pain and urgency 10 cm visual analog scales (VAS)
Time Frame
At every patient visit, up to 2 weeks following initial treatment
Title
Incidence of Treatment-Emergent Adverse Events
Description
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.
Time Frame
At every patient visit, up to 2 weeks following initial treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
University of Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94122
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Michigan Institute of Urology
City
Troy
State/Province
Michigan
ZIP/Postal Code
48084
Country
United States
Facility Name
Premier Medical Group
City
Poughkeepsie
State/Province
New York
ZIP/Postal Code
12603
Country
United States
Facility Name
Temple University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
Allegheny Health Network Research Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15212
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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