Study to Compare Exposure of TA Following Administration of FX006 or TAcs in Patients With OA of the Shoulder or Hip

• Sponsor: Flexion Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03382262
• Collaborator: (none)
• Enrollment: 55
• Locations: 6
• Arms: 2
• Actual Duration (Months): 9.7
• Patients Per Site: 9.2
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This is an open-label study to compare systemic exposure to triamcinolone acetonide following a dose of extended-release FX006 or immediate-release TAcs (triamcinolone acetonide suspension) in patients with osteoarthritis of the shoulder (glenohumeral joint) or hip

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis of the Shoulder; Osteoarthritis of the Hip	Drug: FX006 32 mg; Drug: TAcs 40 mg	Phase 2

Detailed Description

This is a randomized, open-label, single dose study that will be conducted in male and female patients ≥40 years of age with OA of either the shoulder or the hip.

Approximately 24 patients with OA of the shoulder and approximately 24 patients with OA of the hip will be randomized to one of two treatment groups (1:1) and treated with a single IA injection of either:

• 32 mg FX006 (approximately 12 patients per joint) or

• 40 mg TAcs (approximately 12 patients per joint)

Each patient will be screened to confirm the diagnosis of OA of either the shoulder or hip and eligibility based on the other inclusion/exclusion requirements and will be randomized to treatment on Day 1. Each patient will be evaluated for a total of 12 weeks following the IA injection. Following screening, sampling for pharmacokinetics (PK) and safety will be completed at 10 out-patient visits scheduled on Study Days 1 [calendar day of injection], 2, 3, 5, 8, 15, 22, 29, 57, and 85.

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-label Study Comparing the Systemic Exposure to Triamcinolone Acetonide Following a Single Intra-articular Dose of Extended-release FX006 or Immediate-release TAcs (Triamcinolone Acetonide Suspension) in Patients With Osteoarthritis of the Shoulder (Glenohumeral Joint) or Hip
• Actual Study Start Date: Dec 18, 2017
• Actual Primary Completion Date: Oct 9, 2018
• Actual Study Completion Date: Oct 9, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FX006 32 mg Single intra-articular (IA) injection of FX006 32 mg	Drug: FX006 32 mg; Extended-release 32 mg FX006 IA injection; Other Names: Zilretta
Active Comparator: TAcs 40 mg Single intra-articular (IA) injection of TAcs 40 mg	Drug: TAcs 40 mg; Immediate-release 40mg TAcs IA injection; Other Names: Kenalog®-40 Injection Triamcinolone Acetonide Crystalline Suspension (TAcs) TCA-IR 40

Outcome Measures

Primary Outcome Measures

1. Concentration of Triamcinolone Acetonide (TA) in Blood Plasma [12 Weeks]

   Characterize the Pharmacokinetic Profile of FX006 and TCA IR [Time Frame: Day 1 (pre-treatment,1, 2, 3, 4, 5, 6, 8,10, and 12 hrs. post-dose) and Days 2, 3, 5, 8, 15, 22, 29, 57,and 85] For the PK analysis and individual concentration vs. time plots, a concentration that is BLOQ is assigned a value of zero if it occurs in a profile before the first measurable concentration. If a BLOQ value occurs after a measurable concentration in a profile and is followed by a value above the lower limit of quantification, then the BLOQ is treated as missing data. If a BLOQ value occurs at the end of the collection interval (after the last quantifiable concentration) it is set to zero. If two BLOQ values occur in succession after Cmax, the profile is deemed to have terminated at the first BLOQ value and any subsequent concentrations are set to zero for PK calculations

2. Total Number of Treatment Emergent Adverse Events [12 Weeks]

   Analyses of adverse events (AE) were performed for events considered treatment-emergent (TE). TE was defined as any AE with onset after administration of the 1st dose of study drug or any event present at baseline but worsened in intensity through the study. Severity was graded by the PI using the Common Terminology Criteria for AEs Version 4.0. Grading went from Grade 1 (Mild) to Grade 5 (Death Related to AE).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written consent to participate in the study

• Male or female greater than or equal to 40 years of age

• Body mass index (BMI) less than or equal to 40 kg/m2

• Ambulatory and in good general health

• Willing and able to comply with the study procedures and visit schedules and able to follow verbal and written instructions

• Willing to abstain from use of protocol-restricted treatments from Screening through End-of-Study visit

• Symptoms consistent with OA of the index joint for ≥ 6 months prior to Screening (patient reported is acceptable)

• Pain in the index joint for greater than15 days over the last month (as reported by the patient)

• For Shoulder OA patients: Radiologic findings of OA of the index shoulder meeting the Samilson-Prieto (S-P) Classification Grades 2 or 3

• For Hip OA patients: ACR Criteria (clinical and radiological) for OA of the index hip

Exclusion Criteria:

• Reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease

• History of infection in the index joint

• Clinical findings consistent with active infection or crystal disease in the index joint within 1 month of Screening

• History of fracture in the index limb within 12 months of Screening, or fracture with sequelae at any time

• Planned or anticipated surgery of the index joint during the study period

• Index joint instability or history of acute dislocation within 12 months of Screening

• If shoulder is the index joint, history of full or partial rotator cuff tear or significantly compromised rotator cuff function that, in the opinion for the Investigator, increases the difficulty or risk of IA injection

• Presence of surgical hardware or other foreign body in the index joint

• Surgery or arthroscopy of the index joint within 12 months of Screening

• IA treatment of any joint with any of the following agents within 6 months of

Screening:

• Any corticosteroid preparation (investigational or marketed, including FX006), any biologic agent (e.g., platelet rich plasma (PRP) injection, stem cells, prolotherapy, amniotic fluid injection; investigational or marketed)

• IA treatment of the index joint with hyaluronic acid (investigational or marketed) within 6 months of Screening

• Parenteral or oral corticosteroids (investigational or marketed) within 3 months of Screening

• Inhaled, intranasal or topical corticosteroids (investigational or marketed) within 2 weeks of Screening

• Females who are pregnant or nursing or plan to become pregnant during the study; men who plan to conceive during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	TriWest Research Associates, LLC	El Cajon	California	United States	92020
2	Biosolutions Clinical Research Center	La Mesa	California	United States	91942
3	Artemis Institute for Clinical Research	San Diego	California	United States	92103
4	LA Biomed at Harbor-UCLA Medical Center	Torrance	California	United States	90509
5	Rochester Clinical Research	Rochester	New York	United States	14609
6	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635

Sponsors and Collaborators

• Flexion Therapeutics, Inc.

Investigators

• Study Director: Scott Kelley, MD, Flexion Therapeutics, Inc.

Study Documents (Full-Text)

• Study Protocol - Apr 5, 2018
• Statistical Analysis Plan - Oct 17, 2018

More Information

Publications

None provided.

• Responsible Party: Flexion Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03382262
• Other Study ID Numbers: FX006-2017-013
• First Posted: Dec 22, 2017
• Last Update Posted: Dec 9, 2019
• Last Verified: Nov 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Flexion Therapeutics, Inc.: Osteoarthritis; Shoulder; Hip; Pain; Intra-articular; Injection; Corticosteroid
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Hip; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; FX006; Triamcinolone diacetate

Study Results

Participant Flow

Recruitment Details	The recruitment period for this study was from December 2017 to July 2018. The patients were enrolled at medical clinics.

Arm/Group Title	FX006 32 mg Shoulder	TAcs 40 mg Shoulder	FX006 32 mg Hip	TAcs 40 mg Hip
Arm/Group Description	Single intra-articular (IA) injection of FX006 32 mg FX006 32 mg: Extended-release 32 mg FX006 IA injection in the Shoulder	Single intra-articular (IA) injection of TAcs 40 mg TAcs 40 mg: Immediate-release 40mg TAcs IA injection in the Shoulder	Single intra-articular (IA) injection of FX006 32 mg FX006 32 mg: Extended-release 32 mg FX006 IA injection in the Hip	Single intra-articular (IA) injection of TAcs 40 mg TAcs 40 mg: Immediate-release 40mg TAcs IA injection in the Hip
Period Title: Overall Study
STARTED	12	13	15	15
COMPLETED	12	13	14	14
NOT COMPLETED	0	0	1	1

Baseline Characteristics

Arm/Group Title	FX006 32 mg Shoulder	TAcs 40 mg Shoulder	FX006 32 mg Hip	TAcs 40 mg Hip	Total
Arm/Group Description	Single intra-articular (IA) injection of FX006 32 mg in the Shoulder FX006 32 mg: Extended-release 32 mg FX006 IA injection	Single intra-articular (IA) injection of TAcs 40 mg in the Shoulder TAcs 40 mg: Immediate-release 40mg TAcs IA injection	Single intra-articular (IA) injection of FX006 32 mg in the Hip FX006 32 mg: Extended-release 32 mg FX006 IA injection	Single intra-articular (IA) injection of TAcs 40 mg in the Hip TAcs 40 mg: Immediate-release 40mg TAcs IA injection	Total of all reporting groups
Overall Participants	12	13	15	15	55
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.2 (11.39)	61.9 (8.10)	58.1 (7.60)	60.1 (7.09)	60.7 (8.53)
Sex: Female, Male (Count of Participants)
Female	9 75%	6 46.2%	8 53.3%	5 33.3%	28 50.9%
Male	3 25%	7 53.8%	7 46.7%	10 66.7%	27 49.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 25%	0 0%	1 6.7%	1 6.7%	5 9.1%
Not Hispanic or Latino	9 75%	13 100%	14 93.3%	14 93.3%	50 90.9%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	1 6.7%	1 1.8%
Asian	0 0%	0 0%	1 6.7%	0 0%	1 1.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	1 6.7%	0 0%	1 1.8%
Black or African American	1 8.3%	2 15.4%	5 33.3%	5 33.3%	13 23.6%
White	10 83.3%	11 84.6%	8 53.3%	9 60%	38 69.1%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 8.3%	0 0%	0 0%	0 0%	1 1.8%
Region of Enrollment (participants) [Number]
United States	12 100%	13 100%	15 100%	15 100%	55 100%
Body Mass Index (BMI) (kg/mg^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/mg^2]	28.9 (5.98)	30.7 (3.59)	29.3 (3.49)	31.0 (4.40)	30.01 (4.367)

Outcome Measures

1. Primary Outcome

Title	Concentration of Triamcinolone Acetonide (TA) in Blood Plasma
Description	Characterize the Pharmacokinetic Profile of FX006 and TCA IR [Time Frame: Day 1 (pre-treatment,1, 2, 3, 4, 5, 6, 8,10, and 12 hrs. post-dose) and Days 2, 3, 5, 8, 15, 22, 29, 57,and 85] For the PK analysis and individual concentration vs. time plots, a concentration that is BLOQ is assigned a value of zero if it occurs in a profile before the first measurable concentration. If a BLOQ value occurs after a measurable concentration in a profile and is followed by a value above the lower limit of quantification, then the BLOQ is treated as missing data. If a BLOQ value occurs at the end of the collection interval (after the last quantifiable concentration) it is set to zero. If two BLOQ values occur in succession after Cmax, the profile is deemed to have terminated at the first BLOQ value and any subsequent concentrations are set to zero for PK calculations
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

All patients in the Safety population who received study drug, completed scheduled sampling and had sufficient plasma concentration data. 50 of 55 patients were included. Four unique patients for whom hip was the index joint were excluded due to IP administration deviations. One of the four was also found to be enrolled at 2 separate study centers.

Arm/Group Title	FX006 32 mg Shoulder	TAcs 40 mg Shoulder	FX006 32 mg Hip	TAcs 40 mg Hip
Arm/Group Description	Single intra-articular (IA) injection of FX006 32 mg in the Shoulder FX006 32 mg: Extended-release 32 mg FX006 IA injection	Single intra-articular (IA) injection of TAcs 40 mg in the Shoulder TAcs 40 mg: Immediate-release 40mg TAcs IA injection	Single intra-articular (IA) injection of FX006 32 mg in the Hip FX006 32 mg: Extended-release 32 mg FX006 IA injection	Single intra-articular (IA) injection of TAcs 40 mg in the Hip TAcs 40 mg: Immediate-release 40mg TAcs IA injection
Measure Participants	12	13	11	14
Day 1 - Hour 1	1061.8	1104.1	681.8	3862.3
Day 1 - Hour 2	1117.6	1344.8	752.2	4052.4
Day 1 - Hour 3	1140.0	1501.8	748.0	4519.3
Day 1 - Hour 4	1142.4	1594.1	776.1	4557.8
Day 1 - Hour 5	1093.8	1662.7	792.9	4672.6
Day 1 - Hour 6	1052.8	1689.6	743.5	4469.8
Day 1 - Hour 8	1016.2	1668.3	705.0	4102.3
Day 1 - Hour 10	951.4	1506.3	698.2	3615.6
Day 1 - Hour 12	903.8	1531.3	675.1	3276.2
Day 2 - Hour 24	943.4	1467.0	791.0	3218.8
Day - 3	903.4	1413.1	682.1	1723.6
Day - 5	754.6	1038.2	562.4	897.3
Day - 8	678.1	857.8	472.3	525.3
Day - 15	397.6	722.7	382.6	444.7
Day - 22	268.3	476.7	235.0	331.6
Day - 29	201.0	418.7	256.3	281.8
Day - 57	151.8	200	225.1	133.1
Day - 85	100.1	131.4	112.0	92.5

2. Primary Outcome

Title	Total Number of Treatment Emergent Adverse Events
Description	Analyses of adverse events (AE) were performed for events considered treatment-emergent (TE). TE was defined as any AE with onset after administration of the 1st dose of study drug or any event present at baseline but worsened in intensity through the study. Severity was graded by the PI using the Common Terminology Criteria for AEs Version 4.0. Grading went from Grade 1 (Mild) to Grade 5 (Death Related to AE).
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

All patients randomized to receive either FX006 or TAcs in the hip or shoulder.

Arm/Group Title	FX006 32 mg Shoulder	TAcs 40 mg Shoulder	FX006 32 mg Hip	TAcs 40 mg Hip
Arm/Group Description	Single intra-articular (IA) injection of FX006 32 mg in the Shoulder FX006 32 mg: Extended-release 32 mg FX006 IA injection	Single intra-articular (IA) injection of TAcs 40 mg in the Shoulder TAcs 40 mg: Immediate-release 40mg TAcs IA injection	Single intra-articular (IA) injection of FX006 32 mg in the Hip FX006 32 mg: Extended-release 32 mg FX006 IA injection	Single intra-articular (IA) injection of TAcs 40 mg in the Hip TAcs 40 mg: Immediate-release 40mg TAcs IA injection
Measure Participants	12	13	15	15
Number [Events]	10	7	8	17

Adverse Events

Time Frame	Adverse events were collected following IA administration through the final study visit at 12 weeks.
Arm/Group Title	FX006 32 mg Shoulder		TAcs 40 mg Shoulder		FX006 32 mg Hip		TAcs 40 mg Hip
Arm/Group Description	Single intra-articular (IA) injection of FX006 32 mg in the Shoulder FX006 32 mg: Extended-release 32 mg FX006 IA injection		Single intra-articular (IA) injection of TAcs 40 mg in the Shoulder TAcs 40 mg: Immediate-release 40mg TAcs IA injection		Single intra-articular (IA) injection of FX006 32 mg in the Hip FX006 32 mg: Extended-release 32 mg FX006 IA injection		Single intra-articular (IA) injection of TAcs 40 mg in the Hip TAcs 40 mg: Immediate-release 40mg TAcs IA injection
All Cause Mortality
	FX006 32 mg Shoulder		TAcs 40 mg Shoulder		FX006 32 mg Hip		TAcs 40 mg Hip
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/13 (0%)		0/15 (0%)		0/15 (0%)
Serious Adverse Events
	FX006 32 mg Shoulder		TAcs 40 mg Shoulder		FX006 32 mg Hip		TAcs 40 mg Hip
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/13 (0%)		0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	FX006 32 mg Shoulder		TAcs 40 mg Shoulder		FX006 32 mg Hip		TAcs 40 mg Hip
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/12 (33.3%)		3/13 (23.1%)		4/15 (26.7%)		7/15 (46.7%)
Ear and labyrinth disorders
Ear Pain	0/12 (0%)	0	0/13 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Gastrointestinal disorders
Gastrooesophageal Reflux Disease	0/12 (0%)	0	1/13 (7.7%)	1	0/15 (0%)	0	0/15 (0%)	0
Nausea	0/12 (0%)	0	1/13 (7.7%)	1	0/15 (0%)	0	0/15 (0%)	0
General disorders
Influenza Like Illness	1/12 (8.3%)	1	0/13 (0%)	0	0/15 (0%)	0	0/15 (0%)	0
Injection Site Hypoaesthesia	0/12 (0%)	0	0/13 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Infections and infestations
Nasopharyngitis	2/12 (16.7%)	2	0/13 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Upper Respiratory Tract Infection	1/12 (8.3%)	1	0/13 (0%)	0	1/15 (6.7%)	1	1/15 (6.7%)	1
Urinary Tract Infection	1/12 (8.3%)	1	0/13 (0%)	0	0/15 (0%)	0	0/15 (0%)	0
Viral Upper Respiratory Tract Infection	0/12 (0%)	0	0/13 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Injury, poisoning and procedural complications
Contusion	0/12 (0%)	0	0/13 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Fall	0/12 (0%)	0	0/13 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Incision Site Pain	0/12 (0%)	0	0/13 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Periorbital Haemorrhage	0/12 (0%)	0	0/13 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Road Traffic Accident	0/12 (0%)	0	0/13 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Skin Abrasion	0/12 (0%)	0	0/13 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	2
Investigations
Blood Pressure Increased	0/12 (0%)	0	0/13 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Metabolism and nutrition disorders
Gout	0/12 (0%)	0	0/13 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/12 (0%)	0	0/13 (0%)	0	1/15 (6.7%)	1	2/15 (13.3%)	2
Back Pain	0/12 (0%)	0	0/13 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Joint Range of Motion Decreased	1/12 (8.3%)	1	1/13 (7.7%)	1	0/15 (0%)	0	0/15 (0%)	0
Muscular Weakness	0/12 (0%)	0	0/13 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Musculoskeletal Discomfort	1/12 (8.3%)	1	0/13 (0%)	0	0/15 (0%)	0	0/15 (0%)	0
Musculoskeletal Pain	0/12 (0%)	0	1/13 (7.7%)	1	1/15 (6.7%)	1	0/15 (0%)	0
Osteoarthritis	0/12 (0%)	0	1/13 (7.7%)	1	0/15 (0%)	0	0/15 (0%)	0
Pain In Extremity	1/12 (8.3%)	1	0/13 (0%)	0	0/15 (0%)	0	0/15 (0%)	0
Nervous system disorders
Headache	0/12 (0%)	0	0/13 (0%)	0	1/15 (6.7%)	1	1/15 (6.7%)	1
Hypoaesthesia	0/12 (0%)	0	0/13 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Reproductive system and breast disorders
Testicular Pain	0/12 (0%)	0	0/13 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/12 (0%)	0	1/13 (7.7%)	1	0/15 (0%)	0	0/15 (0%)	0
Respiratory Tract Congestion	1/12 (8.3%)	1	0/13 (0%)	0	0/15 (0%)	0	0/15 (0%)	0
Skin and subcutaneous tissue disorders
Melanocytic Hypoplasia	1/12 (8.3%)	1	0/13 (0%)	0	0/15 (0%)	0	0/15 (0%)	0
Vascular disorders
Hot Flush	0/12 (0%)	0	1/13 (7.7%)	1	0/15 (0%)	0	0/15 (0%)	0

Limitations/Caveats

4 patients with hip as index joint, were excluded from the PK population. 3 patients had incomplete FX006 administration. 1 patient enrolled at 2 different study centers; receiving TAcs and FX006 5 days apart in the same hip with no TEAEs reported.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.