A Study to Determine the Safety and Efficacy of Bevacizumab Administered Via Injection Into the Shoulder Joint of Participants With Adhesive Capsulitis (Frozen Shoulder)

This study is intended to test a new treatment for a condition called adhesive capsulitis, also known as frozen shoulder. The treatment being tested is called bevacizumab. Participants will receive a single dose of bevacizumab (50mg, 100mg, 150mg, or 200mg) via injection into their shoulder joint. After the injection, participants will return to site 6 times over the course of a year for safety assessments, questionnaires to track pain levels, and range of movement tests conducted by a physiotherapist. The main goal of this study is to: 1. Evaluate the safety and effectiveness of bevacizumab when it is injected into the frozen shoulder joint. 2. Determine the maximum dose of bevacizumab that can be given without side effects. This is an investigator initiated clinical trial sponsored by Macquarie University. There will be a maximum of 28 participants enrolled and the only site involved in recruitment is Macquarie University.

This study is a single-centred, open-label, dose-ranging clinical trial to assess the safety and efficacy of intra-articular bevacizumab in adults with adhesive capsulitis. Participants, aged 18 years and over, will be included in this study if they are diagnosed with adhesive capsulitis as defined in the inclusion criteria. Eligibility will be dependent on the exclusion of any previous shoulder trauma in the contralateral shoulder, previous adhesive capsulitis or any other differential diagnosis of the ipsilateral shoulder, and serology confirming absence of diabetes mellitus. The dose-ranging follows a classic "3+3 design" to establish dose-limiting toxicities and the recommended dose for future studies. All dose escalations will be determined after a safety evaluation of the prior cohort. The design will be conducted as follows: initially, three participants will be enrolled into cohort 1 and will receive a 50mg dose of bevacizumab. The occurrence of a single treatment-related dose limiting toxicity (defined as a grade 3 or higher adverse event as per Common Terminology Criteria for Adverse Events version 5.0 \[United States of Health and Human Services, 2017\]) will prompt enrolment of three additional participants into the same cohort. When more than one treatment-related dose limiting toxicity occurs in ≤ 6 patients in a dosing cohort, dose escalation will be stopped, and this dose level will be identified as the non-tolerated dose. Otherwise, if ≤ 1 treatment-related dose limiting toxicity occurs in ≤ 6 participants, three participants will be enrolled into the next cohort (cohort 2) and receive a sequentially higher dose of bevacizumab (100mg). This will continue at 50mg increases of bevacizumab for each cohort unless otherwise stopped due to dose-limiting toxicities or Sponsor discretion. The maximum planned dose will be cohort 4 (200mg dose). For this cohort, it is planned to enroll up to 10 participants unless DLTs are observed or enrolment is stopped.