- Inclusion Criteria 9 is changed from requiring that males must use a condom for sexual intercourse until at least 28 days after the last dose of study drug, to requiring that males must use a condom for sexual intercourse until at least 90 days after the last dose of study drug. - Exclusion criterion 1 is changed from a catastrophizing pain score of 30 to ≥30. - Update to O’Leary-Sant Interstitial Cystitis Symptom Index (ICSI) Question 4 - Pregnancy section 12.1.1.1.1 is updated to specify that male subjects, whose partner becomes pregnant during the study and up to 90 days after the last dose of study drug, are instructed to notify the Investigator. Investigators and other site personnel must report any pregnancy that occurs in female subjects and partners of male subjects within 24 hrs of when he or she becomes aware of it to Drug Safety and pregnant partners will be followed until the end of the pregnancy.

- Removal of 14-week extension period (EP) from protocol. All subjects will be eligible to continue into the 40-week open-label extension. - Addition of additional company signatory. - Expansion of potential study participant numbers (minimum of 300 female subjects randomized and maximum of 600 total subjects) and potential study sites to approximately 140 sites. - Recalculation of study timelines. - Addition of an Exploratory Objective to determine the Minimally Clinically Important Difference (MCID) for maximum pain using an anchor based analysis with a Global Response Assessment (GRA) as the anchor. - Add clarity to the definition of Treatment Failure and the Exploratory Objectives assessing proportion of subjects meeting this criterion. - Narrow required specific recorded findings on cystoscopy reports. - Added clarity around follow-up visit timing for subjects participating in the extension period. - Clarity and specificity added to Inclusion Criteria #9 regarding complete abstinence and acceptable methods of contraception. - Updated language in Exclusion Criteria #3 regarding microscopic hematuria - Exclusion Criteria #5 updated to further restrict use of cyclosporine. - From Exclusion Criteria #7, 8 and 9, removed 5-year historical limitation on exposure to some excluded medications or presence of some exclusionary medical conditions. - Table 9.3 Removal of “Expected” from Treatment Emergent Adverse Events table title. - Section 9.5.5 Study Discontinuation language modified based on regulatory requirements. - Section 19 Publication Policy added reference to posting of the trial results to the European Union (EU) Clinical Trials Register

- Extension of the 40-week extension period (EP) to 52 weeks for all treatment arms. All subjects will be eligible to continue into the 52-week extension. - Added 64-week visit (Visit 10) to perform end of treatment activities previously planned for Visit 9. Updated throughout protocol. - Safety objectives updated to the following: Safety and tolerability of AQX-1125 during the 52-week extension period (EP). Safety and tolerability of AQX-1125 over 64 weeks of treatment (combined TP and EP). -Exploratory objective updated to the following: “Evaluation of the proportion of subjects improving by the derived minimum clinically important difference (MCID) in the maximum pain assessment at Week 12 by conducting an anchor-based analysis using the GRA for anchoring to derive the MCID”. - Planned study period updated to reflect updated timelines. - Addition of GRA at Week 64 (Visit 10). - Added clarification and specificity to ocular adverse event reporting - Addition of a Follow-up Telephone Call 3 months post dose. - Addition of an Ophthalmology Safety Visit 6 months post dose. - Addition of the PHQ-9 questionnaire as a screening tool to all study visits up to completion of the EP. - Analysis of the primary efficacy endpoint is changed to analysis using a mixed-effects growth-curve model adjusting for fixed and random covariates (individual, change trajectory, baseline demographic values, and the stratification factors).