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

Phase 2

Terminated

Conditions: Osteoarthritis of the Shoulder
Adhesive Capsulitis

Interventions: Drug: Normal Saline
Drug: FX006

Registration Number: NCT04160091

Lead Sponsor: Pacira Pharmaceuticals, Inc

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 19

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normal Saline in Glenohumeral OA Population	Normal Saline	Single intra-articular (IA) injection
FX006 32mg in Glenohumeral OA Population	FX006	Single intra-articular (IA) injection
FX006 32mg in Adhesive Capsulitis Population	FX006	Single intra-articular (IA) injection
Normal Saline in Adhesive Capsulitis Population	Normal Saline	Single intra-articular (IA) injection

Primary Outcome Measures

Name	Time	Method
Area Under the Curve of the Change From Baseline in the Weekly Mean of the Daily Shoulder Pain With Movement	Baseline to 8 weeks	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."

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in the Weekly Mean of the Average Daily Shoulder Pain With Movement Score	Baseline to 12 weeks	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."
Change From Baseline in the SPADI Pain Subscale at Week 12	Baseline to 12 weeks	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.
Change From Baseline in the SPADI Disability Subscale at Week 12	Baseline to 12 weeks	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.
Patient Global Impression of Change (PGIC) Score at Week 12	Baseline to 12 weeks	PGIC is measured using a 7-point NRS where 1 indicates "very much improved" and 7 indicates "very much worse."
Change From Baseline in the Range of Motion (ROM) of Active External Rotation at Week 12	Baseline to 12 weeks	Measured using a goniometer which is a device that measures ROM joint angles

Trial Locations

Locations (27): Coastal Clinical Research, Inc.
🇺🇸
Mobile, Alabama, United States
Gulfcoast Research Institute
🇺🇸
Sarasota, Florida, United States
Coastal Orthopaedics and Sports Medicine
🇺🇸
Bradenton, Florida, United States
Centex Studies, Inc.
🇺🇸
Houston, Texas, United States
Infinite Clinical Research
🇺🇸
Miami, Florida, United States
Altoona Center for Clinical Research
🇺🇸
Duncansville, Pennsylvania, United States
Hassman Research Institute
🇺🇸
Berlin, New Jersey, United States
South Lake Pain Institute
🇺🇸
Clermont, Florida, United States
Texas Orthopedic Specialists
🇺🇸
Bedford, Texas, United States
Spectrum Medical, Inc.
🇺🇸
Danville, Virginia, United States
M3 Emerging Medical Research
🇺🇸
Durham, North Carolina, United States
Alabama Clinical Therapeutics, LLC
🇺🇸
Birmingham, Alabama, United States
Arizona Research Center
🇺🇸
Phoenix, Arizona, United States
BioSolutions Clinical Research Center
🇺🇸
La Mesa, California, United States
Tucson Orthopaedic Institute
🇺🇸
Tucson, Arizona, United States
Affinity Orthopedic Specialists
🇺🇸
Birmingham, Alabama, United States
TriWest Research Associates
🇺🇸
El Cajon, California, United States
Central Research Associates
🇺🇸
Birmingham, Alabama, United States
Jewitt Orthopedic Center
🇺🇸
Orlando, Florida, United States
CORE Orthopedic Medical Center
🇺🇸
Encinitas, California, United States
Universal Axon Clinical Research
🇺🇸
Homestead, Florida, United States
Better Health Clinical Research, Inc.
🇺🇸
Newnan, Georgia, United States
Professional Research Network of Kansas, LLC
🇺🇸
Wichita, Kansas, United States
University Orthopedics Center
🇺🇸
Altoona, Pennsylvania, United States
Arthritis and Rheumatism Associates PC
🇺🇸
Wheaton, Maryland, United States
Precision Clinical Research
🇺🇸
Lauderdale Lakes, Florida, United States
Mountain View Clinical Research Center
🇺🇸
Denver, Colorado, United States