Efficacy and Safety of AQX-1125 in IC/BPS (LEADERSHIP)

A Phase 2 Study to Evaluate the Efficacy and Safety of AQX-1125 in Subjects With Interstitial Cystitis/Bladder Pain Syndrome Mediated by the Src Homology-2-domain-containing Inositol 5' Phosphatase [SHIP1] Pathway

The primary objective of this study is to evaluate the effect of 6 weeks of treatment with once daily administration of AQX-1125 compared to placebo on average daily pain in subjects with interstitial cystitis/bladder pain syndrome (IC/BPS), during and after treatment, using a standardized 11-point numerical rating scale (NRS) pain score recorded by electronic diary

Study Overview

• Status: Completed
• Conditions: Interstitial Cystitis; Bladder Pain Syndrome
• Intervention / Treatment: Drug: AQX-1125; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2V1P9
      • AQX/CMX site
  • British Columbia
    • Kelowna, British Columbia, Canada
      • AQX/CMX site
    • Vancouver, British Columbia, Canada, V6Z1Y6
      • AQX/CMX site
    • Victoria, British Columbia, Canada
      • AQX/CMX site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H2Y9
      • AQX/CMX site
  • Ontario
    • Barrie, Ontario, Canada
      • AQX/CMX site
    • Brampton, Ontario, Canada
      • AQX/CMX site
    • Brantford, Ontario, Canada
      • AQX/CMX site
    • Burlington, Ontario, Canada
      • AQX/CMX site
    • Kingston, Ontario, Canada
      • AQX/CMX site
    • Kitchener, Ontario, Canada
      • AQX/CMX site
    • Oakville, Ontario, Canada
      • AQX/CMX site
    • Toronto, Ontario, Canada
      • AQX/CMX site
    • Toronto, Ontario, Canada
      • Dr Lesley Carr
  • Quebec
    • Granby, Quebec, Canada
      • AQX/CMX site
    • Montreal, Quebec, Canada
      • AQX/CMX site
    • Sherbrooke, Quebec, Canada
      • AQX/CMX site
• United States
  • Alabama
    • Homewood, Alabama, United States, 35209
      • AQX/CMX site
  • California
    • Glendora, California, United States, 91741
      • AQX/CMX site
    • San Diego, California, United States, 92123
      • AQX/CMX site
  • Colorado
    • Denver, Colorado, United States, 80211
      • AQX/CMX site
  • Connecticut
    • Farmington, Connecticut, United States, 06032
      • AQX/CMX site
  • Florida
    • Orlando, Florida, United States, 32801
      • AQX/CMX site
  • Louisiana
    • Shreveport, Louisiana, United States, 71106
      • AQX/CMX site
  • Michigan
    • Troy, Michigan, United States, 48084
      • AQX/CMX site
  • New York
    • Garden City, New York, United States, 11530
      • AQX/CMX site
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • AQX/CMX site
  • Ohio
    • Toledo, Ohio, United States, 43615
      • AQX/CMX site
  • Texas
    • DeSoto, Texas, United States, 75115
      • AQX/CMX site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Be females, ≥18 and ≤75 years of age, who have consistently had symptoms of bladder pain in addition to urinary urgency and/or urinary frequency for more than 12 months
• Have had the diagnosis of interstitial cystitis for > 6 months (pain for at least 12 months) but ≤15 years
• Have average daily pain score of at least 5 out of 10 on the 11-point Numerical Rating Scale [NRS] pain scale in the 9 days prior to baseline
• Have undergone a cystoscopy and have documented visible signs of bladder bleeding, lesions or glomerulation within the last 36 months prior to baseline.
• Subjects if of child bearing potential, must agree to avoid pregnancy and use medically acceptable method of contraception from screening visit and throughout the study.
• Must be capable of voiding independently

Exclusion Criteria:

• Pelvic floor pain (>5 out of 10 on the 11-point NRS pain scale following a pelvic pain assessment)
• Have a body mass index [BMI] of <18 kg/m2 or >39 kg/m2
• Have had a urinary tract infection including bacterial cystitis within the past 30 days.
• Have greater than 1+ hematuria on dipstick test at screening from an unknown cause
• History of previous procedure(s) (augmentation cystoplasty, cystectomy, or cystolysis) that has affected bladder function

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AQX-1125; 1 x AQX-1125 Capsule daily	Drug: AQX-1125; Synthetic SHIP1 activator
Placebo Comparator: Placebo; 1 x placebo capsule daily	Drug: Placebo; Double blind placebo capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Average Daily Bladder Pain Score (e-Diary)	Change from baseline to week 6 in the average daily bladder pain score using a standardized 11-point numerical rating scale (NRS) recorded by e-diary. The 11-point NRS ranges from 0-10 with 0 indicating 'no pain' and 10 indicating 'worst pain'.	Baseline to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Maximum Daily Bladder Pain Score (e-Diary)	Change from baseline to week 6 in the maximum daily bladder pain score using a standardized 11-point numerical rating scale (NRS) recorded by e-diary. The 11-point NRS ranges from 0-10 with 0 indicating 'no pain' and 10 indicating 'worst pain'.	Baseline to Week 6
Change From Baseline in the Average Bladder Pain Score (Clinic)	Change from baseline to week 6 in the average daily bladder pain score using a standardized 11-point numerical rating scale (NRS) recorded at study visit. The 11-point NRS ranges from 0-10 with 0 indicating 'no pain' and 10 indicating 'worst pain'.	Baseline to Week 6
Change From Baseline in the Maximum Bladder Pain Score (Clinic)	Change from baseline to week 6 in the maximum daily bladder pain score using a standardized 11-point numerical rating scale (NRS) recorded at study visits. The 11-point NRS ranges from 0-10 with 0 indicating 'no pain' and 10 indicating 'worst pain'.	Baseline to Week 6
Bladder Pain/Interstitial Cystitis Symptom Score [BPIC-SS]	Change in baseline to week 6 in the BPIC-SS participant reported questionnaire total score. The total BPIC-SS score ranges from 0-38, with a higher score indicative of worse symptoms. A score of 19 or more was considered to be discriminating between IC/BPS and overactive bladder at screening.	Baseline to Week 6
O'Leary-Sant Interstitial Cystitis Symptom Index/Problem Index [ICSI/PI]	Change from baseline to week 6 in the O'Leary Sant Symptom and Problem Index combined total scores. Both the ICSI and ICPI consist of 4 questions with responses for the ICSI rated on a scale of 0-5 (maximum score of 20, with a higher score indicating worse symptoms) and for the ICPI on a scale of 0-4 (maximum score of 16, with a higher score indicating worse symptoms). For the combined ICSI/PI the maximum score is 36, with a higher score indicating worse symptoms.	Baseline to Week 6
Short Form 12 Version 2.0 Health Survey [SF-12v2] Questionnaire	Change from baseline to week 6 in the SF-12v2 questionnaire. Two parameters, PCS (physical component summary) and MCS (mental component summary) were calculated. Both components scores range from 0 to 100 with higher scores indicating better Quality of Life.	Baseline to Week 6
Voiding Frequency as Recorded by Diary Over a 24 Hour Period	For a 24-hour period (within 3 days of the subsequent visit), subjects recorded the frequency of each void prior to visit. The outcome measure was the change from baseline at week 6.	Baseline to Week 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
AQX-1125 Concentrations in Plasma and Urine (Trough Values)	AQX-1125 Plasma and Urine Concentrations were measured at week 4 and week 6.	Week 4 and Week 6

Collaborators and Investigators

• Sponsor: Aquinox Pharmaceuticals (Canada) Inc.
• Investigators: Study Director: Stephen B Shrewsbury, MD, Aquinox Pharmaceuticals (Canada) Inc.

Publications and helpful links

General Publications

• Imamura M, Scott NW, Wallace SA, Ogah JA, Ford AA, Dubos YA, Brazzelli M. Interventions for treating people with symptoms of bladder pain syndrome: a network meta-analysis. Cochrane Database Syst Rev. 2020 Jul 30;7(7):CD013325. doi: 10.1002/14651858.CD013325.pub2.

Helpful Links

• The Interstitial Cystitis Association (ICA) is the only nonprofit association dedicated solely to improving the quality of healthcare and lives of people living with interstitial cystitis (IC).

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: June 18, 2013
• First Submitted That Met QC Criteria: June 18, 2013
• First Posted (Estimate): June 20, 2013

Study Record Updates

• Last Update Posted (Actual): September 5, 2017
• Last Update Submitted That Met QC Criteria: August 3, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Interstitial cystitis; Bladder pain syndrome; IC/BPS; AQX-1125; SHIP1
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Urinary Bladder Diseases; Disease; Syndrome; Cystitis; Cystitis, Interstitial
• Other Study ID Numbers: AQX-1125-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO