Clinical trial NCT04160091: Study to Evaluate the Efficacy and Safety of FX006 in Patients With Glenohumeral Osteoarthritis or Shoulder Adhesive Capsulitis
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Osteoarthritis of the Shoulder
Adhesive Capsulitis
Keywords: Osteoarthritis
Adhesive Capsulitis
Shoulder
Pain
Intra-articular
Injection
Steroid
Lead sponsor: Pacira Pharmaceuticals, Inc
Sponsor class: INDUSTRY
Collaborators: name: Medpace, Inc.
First posted: 2019-11-12
Enrollment: 19
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Curve of the Change From Baseline in the Weekly Mean of the Daily Shoulder Pain With Movement
timeFrame: Baseline to 8 weeks
Secondary outcomes:
measure: Change From Baseline in the Weekly Mean of the Average Daily Shoulder Pain With Movement Score
timeFrame: Baseline to 12 weeks
measure: Change From Baseline in the SPADI Pain Subscale at Week 12
timeFrame: Baseline to 12 weeks
measure: Change From Baseline in the SPADI Disability Subscale at Week 12
timeFrame: Baseline to 12 weeks
measure: Patient Global Impression of Change (PGIC) Score at Week 12
timeFrame: Baseline to 12 weeks
measure: Change From Baseline in the Range of Motion (ROM) of Active External Rotation at Week 12
timeFrame: Baseline to 12 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Central Research Associates
state: Alabama
city: Birmingham
country: United States
facility: Alabama Clinical Therapeutics, LLC
state: Alabama
city: Birmingham
country: United States
facility: Affinity Orthopedic Specialists
state: Alabama
city: Mobile
country: United States
facility: Coastal Clinical Research, Inc.
state: Alabama
city: Phoenix
country: United States
facility: Arizona Research Center
state: Arizona
city: Tucson
country: United States
facility: Tucson Orthopaedic Institute
state: Arizona
city: El Cajon
country: United States
facility: TriWest Research Associates
state: California
city: Encinitas
country: United States
facility: CORE Orthopedic Medical Center
state: California
city: La Mesa
country: United States
facility: BioSolutions Clinical Research Center
state: California
city: Denver
country: United States
facility: Mountain View Clinical Research Center
state: Colorado
city: Bradenton
country: United States
facility: Coastal Orthopaedics and Sports Medicine
state: Florida
city: Clermont
country: United States
facility: South Lake Pain Institute
state: Florida
city: Homestead
country: United States
facility: Universal Axon Clinical Research
state: Florida
city: Lauderdale Lakes
country: United States
facility: Precision Clinical Research
state: Florida
city: Miami
country: United States
facility: Infinite Clinical Research
state: Florida
city: Orlando
country: United States
facility: Jewitt Orthopedic Center
state: Florida
city: Sarasota
country: United States
facility: Gulfcoast Research Institute
state: Florida
city: Newnan
country: United States
facility: Better Health Clinical Research, Inc.
state: Georgia
city: Wichita
country: United States
facility: Professional Research Network of Kansas, LLC
state: Kansas
city: Wheaton
country: United States
facility: Arthritis and Rheumatism Associates PC
state: Maryland
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Durham
country: United States
facility: M3 Emerging Medical Research
state: North Carolina
city: Altoona
country: United States
facility: University Orthopedics Center
state: Pennsylvania
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Bedford
country: United States
facility: Texas Orthopedic Specialists
state: Texas
city: Houston
country: United States
facility: Centex Studies, Inc.
state: Texas
city: Danville
country: United States
facility: Spectrum Medical, Inc.
state: Virginia
Study officials:
affiliation: Pacira Pharmaceuticals, Inc
name: Scott Kelley, MD
role: STUDY_DIRECTOR
References: