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

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)

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).

Study Overview

• Status: Terminated
• Conditions: Adhesive Capsulitis; Osteoarthritis of the Shoulder
• Intervention / Treatment: Drug: FX006; Drug: Normal Saline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • Alabama Clinical Therapeutics, LLC
    • Birmingham, Alabama, United States, 35205
      • Central Research Associates
    • Birmingham, Alabama, United States, 35243
      • Affinity Orthopedic Specialists
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research, Inc.
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Arizona Research Center
    • Tucson, Arizona, United States, 85712
      • Tucson Orthopaedic Institute
  • California
    • El Cajon, California, United States, 92020
      • TriWest Research Associates
    • Encinitas, California, United States, 92924
      • CORE Orthopedic Medical Center
    • La Mesa, California, United States, 91924
      • BioSolutions Clinical Research Center
  • Colorado
    • Denver, Colorado, United States, 80209
      • Mountain View Clinical Research Center
  • Florida
    • Bradenton, Florida, United States, 34209
      • Coastal Orthopaedics and Sports Medicine
    • Clermont, Florida, United States, 34711
      • South Lake Pain Institute
    • Homestead, Florida, United States, 33030
      • Universal Axon Clinical Research
    • Lauderdale Lakes, Florida, United States, 33319
      • Precision Clinical Research
    • Miami, Florida, United States, 33133
      • Infinite Clinical Research
    • Orlando, Florida, United States, 32822
      • Jewitt Orthopedic Center
    • Sarasota, Florida, United States, 34232
      • Gulfcoast Research Institute
  • Georgia
    • Newnan, Georgia, United States, 30265
      • Better Health Clinical Research, Inc.
  • Kansas
    • Wichita, Kansas, United States, 67205
      • Professional Research Network of Kansas, LLC
  • Maryland
    • Wheaton, Maryland, United States, 20902
      • Arthritis and Rheumatism Associates PC
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
  • North Carolina
    • Durham, North Carolina, United States, 22704
      • M3 Emerging Medical Research
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • University Orthopedics Center
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • Texas
    • Bedford, Texas, United States, 76021
      • Texas Orthopedic Specialists
    • Houston, Texas, United States, 77058
      • Centex Studies, Inc.
  • Virginia
    • Danville, Virginia, United States, 24541
      • Spectrum Medical, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pacira Pharmaceuticals, Inc
• Collaborators: Medpace, Inc.
• Investigators: Study Director: Scott Kelley, MD, Pacira Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2019
• Primary Completion (Actual): June 15, 2020
• Study Completion (Actual): June 15, 2020

Study Registration Dates

• First Submitted: November 8, 2019
• First Submitted That Met QC Criteria: November 8, 2019
• First Posted (Actual): November 12, 2019

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Osteoarthritis; Pain; Shoulder; Steroid; Adhesive Capsulitis; Intra-articular; Injection
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Bursitis; Physiological Effects of Drugs; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; FX006
• Other Study ID Numbers: FX006-2018-016

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No