Study to Evaluate the Efficacy and Safety of FX006 in Patients With Glenohumeral Osteoarthritis or Shoulder Adhesive Capsulitis

Study Overview
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Brief Summary
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This is a double-blind study to evaluate the efficacy and safety of FX006 in patients with glenohumeral osteoarthritis (OA) or shoulder adhesive capsulitis (AC).

Detailed Description
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This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group study in separate cohorts of patients with a documented history of either glenohumeral OA or shoulder AC. Glenohumeral OA and shoulder AC patients will be randomized to receive a single intra-articular injection of either FX006 or placebo (saline) in a 1:1 ratio to the index shoulder with a 24-week Treatment Evaluation Period. Glenohumeral OA patients will be stratified by Baseline average daily shoulder pain with movement score according to the following classifications: 5.0 to <7.0 or ≥7.0 to 9.0 (0 to 10 numeric rating scale [NRS]). Shoulder AC patients will be stratified by Baseline average daily shoulder pain with movement score according to the following classifications: 5.0 to <7.0 or ≥7.0 to 9.0 (0 to 10 NRS), and by pain duration since onset (1 to 3 months, inclusive, or >3 to ≤6 months). A Home Exercise Program will be implemented 3 days following injection for shoulder AC patients.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of FX006 in Patients With Glenohumeral Osteoarthritis or Shoulder Adhesive Capsulitis (RANGE)

Conditions
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Osteoarthritis of the Shoulder, Adhesive Capsulitis

Intervention / Treatment
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* Drug: FX006
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Glenohumeral OA: Male or female, 35 to 80 years of age, inclusive, on the day of consent. Painful symptoms associated with OA of the index glenohumeral joint for ≤3 months prior to the Screening Visit. Grade 2 or 3 OA in the index glenohumeral joint based on the Samilson-Prieto classification system as confirmed by X-ray (axillary view and true anterior-posterior view) taken at the Screening Visit. Shoulder AC: Male or female, 35 to 80 years of age, inclusive, on the day of consent. Pain associated with AC of the index joint for ≥1 month but ≤ 6 months prior to the Screening Visit. Limitations on both active and passive ROM ≥25% in at least 2 directions (e.g., forward flexion, abduction, and internal and external rotation assessed in a standardized protocol) compared with the contralateral shoulder or with normal values. No X-ray evidence of OA of the index shoulder (axillary view and true anterior-posterior view) at the Screening Visit. Agrees to complete a standardized, protocol-specified shoulder Home Exercise Program (HEP) starting 3 days after injection until the End of Study (EOS) Visit. Both: Written consent to participate in the study Willing and able to comply with the study procedures and visit schedules and able to follow verbal and written instructions (BMI) ≤ 40 kg/m2 Average daily mean shoulder pain with movement score ≥5.0 and ≤9.0 in the index shoulder (0 to 10 NRS) using the average daily ratings for at least 5 out of the 7 days prior to Day 1. Shoulder pain present >15 days in the month prior to the Screening Visit Willing to complete a washout of protocol-specified excluded medications 7 days prior to Day 1 and abstain from use of protocol-specified excluded medications throughout the study Willing to abstain from nonpharmacological therapies for the index joint for 2 weeks prior to Day 1 and throughout the study. Exclusion Criteria: Has both glenohumeral OA and shoulder AC Has bilateral AC Has bilateral glenohumeral OA with glenohumeral OA pain of the shoulder contralateral to the index shoulder >3.0 (0 to 10 NRS) within 1 month prior to the Screening Visit Has a history of arthritis in other joints of the index shoulder (as confirmed by medical history and physical exam) Has a history or suspicion of full thickness rotator cuff tear in the index shoulder within 6 months of the Screening Visit Has symptomatic partial rotator cuff tear, tendinopathy, tendonitis, or bursitis in the index shoulder within 6 months of the Screening Visit Has a subchondral bone insufficiency fracture or humeral head necrosis/collapse in the index shoulder Shoulder AC patients only: Has a history of shoulder surgery or radiotherapy Glenohumeral OA patients only: Has a previous shoulder injury with functional limitation ≥1 month or surgery within 52 weeks of the Screening Visit Has an index shoulder with major dysplasia or congenital abnormality, osteochondritis dissecans, acromegaly, ochronosis, hemochromatosis, Wilson's disease, or primary osteochondromatosis, or a history of avascular necrosis with secondary OA Has current or history of infection in the index shoulder or current skin infection at injection site Has a concurrent chronic pain condition with a pain score >3.0 (0 to 10 NRS) within 1 month prior to the Screening Visit Has a history or current evidence of reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease, systemic lupus erythematosus, calcium pyrophosphate dihydrate crystal deposition disease (CPPD), or other autoimmune diseases Has any planned surgeries in the upper limbs during the study or any other surgery during the study that would require use of a restricted medication Has surgical hardware or other foreign body present in the index shoulder Has received an IA corticosteroid of any joint within 3 months of the Screening Visit Has received an IA treatment of the index shoulder with any of the following agents within 6 months of the Screening Visit Has received intravenous (IV), intrabursal, intratendinous, intramuscular (IM) or epidural corticosteroids within 3 months of the Screening Visit Has received oral corticosteroids within 1 month of the Screening Visit Has received inhaled, intranasal, or topical corticosteroids within 2 weeks of the Screening Visit Has had significant changes to lifestyle with regard to physical activity and lifestyle within 1 month of the Screening Visit or any planned changes throughout the duration of the study Has known hypersensitivity to TA or PLGA Has laboratory evidence of infection with (HIV), a positive test for hepatitis B surface antigen (HBsAg), or positive serology for hepatitis C virus (HCV) with positive test for HCV ribonucleic acid Has an electrocardiogram (ECG) abnormality Has uncontrolled diabetes as indicated by a hemoglobin A1c of >8% (>59 mmol/mol). Has a history of sarcoidosis or amyloidosis Has a history of or active Cushing's syndrome Has used chemotherapeutic agents, immunomodulators, or immunosuppressants within 5 years of the Screening Visit Has current or history of malignancy within 5 years prior to the Screening Visit, except for basal or squamous cell carcinoma of the skin or cervical carcinoma in situ that has been treated successfully. Has active substance use disorder or history of substance use disorder within 12 months prior to the Screening Visit Has received a live or live attenuated vaccine within 3 months of the Screening Visit Has used any other investigational drug, biologic, or device within 3 months of the Screening Visit Has any infection requiring IV antibiotics 4 weeks prior to Day 1 or oral antibiotics 2 weeks prior to Day 1 Has a contraindication to the use of acetaminophen Is a female that is pregnant or nursing or plans to become pregnant during the study; or is a male who plans to inseminate a partner or donate sperm during the study

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FX006 32mg in Glenohumeral OA Population<br>Single intra-articular (IA) injection | Drug: FX006<br>* Single intra-articular injection<br>* Other names: Zilretta;|
| Placebo Comparator: Normal Saline in Glenohumeral OA Population<br>Single intra-articular (IA) injection | Drug: Normal Saline<br>* Single intra-articular injection<br>|
| Experimental: FX006 32mg in Adhesive Capsulitis Population<br>Single intra-articular (IA) injection | Drug: FX006<br>* Single intra-articular injection<br>* Other names: Zilretta;|
| Placebo Comparator: Normal Saline in Adhesive Capsulitis Population<br>Single intra-articular (IA) injection | Drug: Normal Saline<br>* Single intra-articular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve of the Change From Baseline in the Weekly Mean of the Daily Shoulder Pain With Movement | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates No pain and 10 indicates Worst possible pain. | Baseline to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Weekly Mean of the Average Daily Shoulder Pain With Movement Score | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates No pain and 10 indicates Worst possible pain. | Baseline to 12 weeks | 
| Change From Baseline in the SPADI Pain Subscale at Week 12 | Shoulder Pain and Disability Index (SPADI) Pain scale is measured using 5 11-point NRS questions where 0 indicates no pain and 10 indicates worst pain imaginable. The Pain and Disability Subscales are presented as a percentage of the total possible score. The Total SPADI score ranges from 0 (best) to 100 (worst) is computed by taking the means of the Pain and Disability Subscale scores. | Baseline to 12 weeks | 
| Change From Baseline in the SPADI Disability Subscale at Week 12 | Shoulder Pain and Disability Index (SPADI) Disability scale is measured using 8 11-point NRS questions where 0 indicates no difficulty and 10 indicates so difficult it requires help. The Pain and Disability Subscales are presented as a percentage of the total possible score. The Total SPADI score ranges from 0 (best) to 100 (worst) is computed by taking the means of the Pain and Disability Subscale scores. | Baseline to 12 weeks | 
| Patient Global Impression of Change (PGIC) Score at Week 12 | PGIC is measured using a 7-point NRS where 1 indicates very much improved and 7 indicates very much worse. | Baseline to 12 weeks | 
| Change From Baseline in the Range of Motion (ROM) of Active External Rotation at Week 12 | Measured using a goniometer which is a device that measures ROM joint angles | Baseline to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Adhesive Capsulitis, Shoulder, Pain, Intra-articular, Injection, Steroid