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

NCT06976671 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MQ-SR-001
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.Evaluate the safety and effectiveness of bevacizumab when it is injected into the frozen shoulder joint.
2. 2.Determine the maximum dose of bevacizumab that can be given without side effects.

Conditions

Adhesive Capsulitis

Keywords

Adhesive Capsulitis; Frozen Shoulder

Outcome Measures

Primary Outcomes (2)

• Evaluate the safety of bevacizumab over a 52-week period in participants with adhesive capsulitis

  * Incidence of adverse events (including medically significant changes in physical assessments, laboratory assessments, vital signs, and electrocardiogram), and serious adverse events, at 7 days (V3), 14 days (V4), 28 days (V5), 84 days (V6), 168 days (V7), and 364 days (V8) * Incidence of adverse events and serious adverse events at 3 days (V2)

  52 Weeks

• Determine the maximum tolerated dose of intra-articular bevacizumab at 1 week (V3) per cohort

  Maximum tolerated dose as defined as the highest dose where 0 out of 3 participants or no more than 1 out of 6 participants experienced any dose-limiting toxicity (defined as a grade 3 or higher adverse event as per Common Terminology Criteria for Adverse Events version 5.0

  From start of treatment to 1 week after treatment

Secondary Outcomes (5)

• Evaluate the efficacy of bevacizumab over a 52-week period in participants with adhesive capsulitis

  52 weeks

• Evaluate the efficacy of bevacizumab over a 52-week period in participants with adhesive capsulitis

  52 weeks

• Evaluate the efficacy of bevacizumab over a 52-week period in participants with adhesive capsulitis

  52 weeks

• Evaluate the efficacy of bevacizumab over a 52-week period in participants with adhesive capsulitis

  52 weeks

• Evaluate the efficacy of bevacizumab over a 52-week period in participants with adhesive capsulitis

  52 weeks

Other Outcomes (5)

• Evaluate the safety of bevacizumab over a 52-week period in participants with adhesive capsulitis

  52 Weeks

• Evaluate the efficacy of bevacizumab over a 24-week period in participants with adhesive capsulitis

  24 weeks

• Evaluate the efficacy of bevacizumab over a 24-week period in participants with adhesive capsulitis

  24 weeks

Study Arms (1)

Intra-articular Bevacizumab

EXPERIMENTAL

Bevacizumab administered as a single-dose intra-articular injection at 4 dose levels (50mg, 100mg, 150mg, 200mg)

Drug: Bevacizumab

Interventions

Bevacizumab DRUG

intra-articular bevacizumab

Intra-articular Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• IC1. Over 18 years of age (inclusive) at the time of signing informed consent
• IC2. Clinical diagnosis of adhesive capsulitis which is defined as:
• Progressive pain and stiffness for a period greater than 2 months but less than 6 months; and,
• Either thickening or signal hyperintensity associated with coracohumeral ligament, axillary pouch, or rotator interval joint capsule OR obliteration of the subcoracoid fat triangle as confirmed by radiological examination (magnetic resonance imaging); and,
• Normal x-ray of the shoulder with no evidence of glenohumeral joint degenerative changes or sequelae of previous trauma.
• IC3. Capable of giving signed informed consent as described in Section 14 of the protocol which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol
• IC4. Participants of child-bearing potential are eligible to participate if they agree to the following during the study intervention period and for a minimum of 120 days after the study intervention is administered:
• Female participants must not be pregnant or breastfeeding AND are either abstinent from heterosexual intercourse as their preferred usual lifestyle OR engage in an adequate method of contraception (i.e., the oral contraceptive pill, intrauterine device, or other)
• Male participants must refrain from donating sperm AND are either abstinent from heterosexual intercourse as their preferred usual lifestyle OR must agree to use an adequate method of contraception/barrier method (i.e. condom and/or heterosexual partner engaging in an adequate method of contraception as previously described)
• IC5. Participants who are not of child-bearing potential, defined as at least one or more of the following criteria, are eligible to participate in the study
• Female participants in a post-menopausal state (defined as not experiencing menses for 12 consecutive months without an alternative cause)
• Documented permanent sterilisation method (including, but not limited to, hysterectomy, bilateral salpingectomy, bilateral oophorectomy, and vasectomy)

You may not qualify if:

• EC1. History of previous surgery or treatment with corticosteroid prior to screening, platelet-rich plasma, or anti-VEGF injections in the ipsilateral shoulder
• EC2. History of adhesive capsulitis in ipsilateral shoulder
• EC3. Presence of trauma in the affected shoulder unrelated to adhesive capsulitis
• EC4 Advanced imaging features associated with calcific tendinopathy
• EC5. Presence of uncontrolled hypertension (defined as systolic pressure \> 140mmHg and diastolic pressure \> 100mmHg)
• EC6. Any medical history of cardiovascular disease, uncontrolled ischemic heart disease, acute myocardial infarction within 12 months of study entry, or any history of intracranial hemorrhage, stroke or a transient ischaemic attacks at any time
• EC7. Presence of inflammatory arthritis (such as but not limited to: systemic lupus erythematosus, rheumatoid arthritis, reactive arthritis, etc.), Parkinson's disease, brain injury, osteoarthritis, bony glenohumeral pathology, hypothyroidism, neuromuscular disorders, or pre-diabetes or diabetes mellitus (defined by fasting glucose ≥7mmol/L and Hba1c ≥ 5.7%)
• EC8. Participants currently taking corticosteroids, monoclonal antibody therapy, or other immunosuppressants which are deemed to impact the study endpoints
• EC9. Planning to or have received treatment for the affected shoulder at any time during the study or prior to the study included but not limited to:
• Intra-articular or intrabursal injection(s) of lidocaine, suprascapular nerve blocks; corticosteroids, electroanalgesic and/or thermoanalgesic modalities
• Intra-articular or intrabursal injection(s) of sodium hyaluronate and/or glenohumeral distension arthrography
• Surgical intervention
• EC10. Progressive pain and stiffness in the affected shoulder that is for a period less than 2 months or greater than 6 months
• EC11. Hypersensitivity to the study intervention, including any constituents thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study
• EC12. Any active malignancy under treatment

Sponsors & Collaborators

• Macquarie University, Australia: lead

Study Sites (1)

Macquarie University

North Ryde, New South Wales, 2109, Australia

RECRUITING

MeSH Terms

Conditions

Bursitis

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Sumit Raniga, BSC, MSC, MBCHB, FRACS, FAORTH

  Macquarie Unniversity

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sumit Raniga, BSC, MSC, MBCHB, FRACS, FAORTH

CONTACT

+61 2 9812 3583; sumit.raniga@mqhealth.org.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will receive a single intra-articular dose of 50mg bevacizumab. This dose will increase sequentially by 50mg per treatment cohort, until otherwise stopped due to dose-limiting toxicities or Sponsor discretion. 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 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 occur

Study Record Dates

• First Submitted: September 10, 2024
• First Posted: May 16, 2025
• Study Start: September 10, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: May 16, 2025

Record last verified: 2024-09

Locations

AU (1)