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)

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04160091

Enrollment

Registered

2019-11-12

Start date

2019-11-07

Completion date

2020-06-15

Last updated

2024-01-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Adhesive Capsulitis, Osteoarthritis of the Shoulder

Keywords

Osteoarthritis, Adhesive Capsulitis, Shoulder, Pain, Intra-articular, Injection, Steroid

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.

Interventions

DRUGFX006

Single intra-articular injection

DRUGNormal Saline

Single intra-articular injection

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

35 Years to 80 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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

Countries

United States

Participant flow

Participants by arm

Arm	Count
FX006 32mg in Glenohumeral OA Population Single intra-articular (IA) injection FX006: Single intra-articular injection	7
Normal Saline in Glenohumeral OA Population Single intra-articular (IA) injection Normal Saline: Single intra-articular injection	3
FX006 32mg in Adhesive Capsulitis Population Single intra-articular (IA) injection FX006: Single intra-articular injection	5
Normal Saline in Adhesive Capsulitis Population Single intra-articular (IA) injection Normal Saline: Single intra-articular injection	4
Total	19

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Noncompliance	0	0	0	1
Overall Study	Terminated by Sponsor	7	3	5	2
Overall Study	Withdrawal by Subject	0	0	0	1

Baseline characteristics

Characteristic	FX006 32mg in Adhesive Capsulitis Population	Normal Saline in Adhesive Capsulitis Population	Total	FX006 32mg in Glenohumeral OA Population	Normal Saline in Glenohumeral OA Population
Age, Continuous Adhesive Capsulitis Population	56.2 years STANDARD_DEVIATION 12.64	58.5 years STANDARD_DEVIATION 4.8	57.2 years STANDARD_DEVIATION 9.48	—	—
Age, Continuous OA Population	—	—	61.2 years STANDARD_DEVIATION 10.78	61.7 years STANDARD_DEVIATION 13.07	60.0 years STANDARD_DEVIATION 2.65
Body Mass Index (BMI) Adhesive Capsulitis Population	33.03 kg/m^2 STANDARD_DEVIATION 4.425	27.99 kg/m^2 STANDARD_DEVIATION 6.752	30.79 kg/m^2 STANDARD_DEVIATION 5.826	—	—
Body Mass Index (BMI) OA Population	—	—	29.45 kg/m^2 STANDARD_DEVIATION 2.799	28.95 kg/m^2 STANDARD_DEVIATION 2.473	30.61 kg/m^2 STANDARD_DEVIATION 3.744
Ethnicity (NIH/OMB) Adhesive Capsulitis Population Hispanic or Latino	1 Participants	0 Participants	1 Participants	—	—
Ethnicity (NIH/OMB) Adhesive Capsulitis Population Not Hispanic or Latino	4 Participants	4 Participants	8 Participants	—	—
Ethnicity (NIH/OMB) Adhesive Capsulitis Population Unknown or Not Reported	0 Participants	0 Participants	0 Participants	—	—
Ethnicity (NIH/OMB) OA Population Hispanic or Latino	—	—	1 Participants	1 Participants	0 Participants
Ethnicity (NIH/OMB) OA Population Not Hispanic or Latino	—	—	9 Participants	6 Participants	3 Participants
Ethnicity (NIH/OMB) OA Population Unknown or Not Reported	—	—	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Adhesive Capsulitis Population American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	—	—
Race (NIH/OMB) Adhesive Capsulitis Population Asian	0 Participants	0 Participants	0 Participants	—	—
Race (NIH/OMB) Adhesive Capsulitis Population Black or African American	1 Participants	0 Participants	1 Participants	—	—
Race (NIH/OMB) Adhesive Capsulitis Population More than one race	0 Participants	0 Participants	0 Participants	—	—
Race (NIH/OMB) Adhesive Capsulitis Population Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	—	—
Race (NIH/OMB) Adhesive Capsulitis Population Unknown or Not Reported	0 Participants	0 Participants	0 Participants	—	—
Race (NIH/OMB) Adhesive Capsulitis Population White	4 Participants	4 Participants	8 Participants	—	—
Race (NIH/OMB) OA Population American Indian or Alaska Native	—	—	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) OA Population Asian	—	—	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) OA Population Black or African American	—	—	2 Participants	1 Participants	1 Participants
Race (NIH/OMB) OA Population More than one race	—	—	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) OA Population Native Hawaiian or Other Pacific Islander	—	—	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) OA Population Unknown or Not Reported	—	—	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) OA Population White	—	—	7 Participants	6 Participants	1 Participants
Region of Enrollment United States	5 participants	4 participants	19 participants	7 participants	3 participants
Sex: Female, Male Adhesive Capsulitis Population Female	4 Participants	3 Participants	7 Participants	—	—
Sex: Female, Male Adhesive Capsulitis Population Male	1 Participants	1 Participants	2 Participants	—	—
Sex: Female, Male OA Population Female	—	—	2 Participants	1 Participants	1 Participants
Sex: Female, Male OA Population Male	—	—	8 Participants	6 Participants	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 7	0 / 3	0 / 5	0 / 4
other Total, other adverse events	1 / 7	0 / 3	2 / 5	0 / 4
serious Total, serious adverse events	0 / 7	0 / 3	0 / 5	0 / 4

Outcome results

Primary

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.

Time frame: Baseline to 8 weeks

Population: Due to the early termination of the study, this endpoint was not analyzed. Change from baseline in the weekly mean of the average daily shoulder pain with movement score is included in Outcome Measure 2

Secondary