Study to Characterize the PK and Local Extent and Duration of Exposure From FX006 in Patients With OA of the Knee

• Sponsor: Flexion Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02637323
• Collaborator: (none)
• Enrollment: 81
• Locations: 4
• Arms: 2
• Duration (Months): 10
• Patients Per Site: 20.3
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

The objectives of this study were to characterize the local extent and duration of exposure of TA from FX006 and TCA IR, characterize the systemic PK of FX006 and TCA IR, and assess the safety and general tolerability of a single 5 mL IA injection of 32 mg FX006 relative to 40 mg of TCA IR in patients with OA of the knee.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis of the Knee	Drug: FX006 32 mg; Drug: TCA IR 40	Phase 2

Detailed Description

This study employed an open-label, single administration design and was conducted in male and female patients ≥40 years of age with OA of the knee.

Patients were enrolled sequentially with at least 10 patients per cohort as follows:

Cohort A: FX006 32 mg, Final Visit at Week 20 Cohort B: FX006 32 mg, Final Visit at Week 16 Cohort C: FX006 32 mg, Final Visit at Week 12 Cohort D: FX006 32 mg, Final Visit at Week 6 Cohort E: FX006 32 mg, Final Visit at Week 1 Cohort F: TCA IR 40 mg, Final Visit Week 6

Each patient was screened to confirm eligibility and assigned to a cohort on Day 1/baseline. Each patient was evaluated for safety during his/her participation in the study at 6, 12, 16, or 20 weeks following a single IA injection depending on the assigned Cohort, and plasma and synovial fluid was collected for drug concentration measurements.

Safety and tolerability was assessed by physical examinations, index knee examinations, vital signs, clinical laboratory evaluations, and adverse events (AEs).

No efficacy assessments were employed in this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Single Administration Study to Characterize the Systemic Pharmacokinetics and Local Extent and Duration of Exposure of Triamcinolone Acetonide From FX006 in Patients With Osteoarthritis of the Knee
• Study Start Date: Nov 1, 2015
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FX006 32 mg Single 5 mL intra-articular (IA) injection Extended-release formulation	Drug: FX006 32 mg; Single 5 mL IA injection; Other Names: Zilretta
Active Comparator: TCA IR 40 mg Commercially available triamcinolone acetonide, single 1 mL intra-articular (IA) injection Immediate-release formulation	Drug: TCA IR 40; Single 1 mL IA injection; Other Names: Kenalog®-40 Injection Triamcinolone Acetonide Crystalline Suspension (TAcs)

Outcome Measures

Primary Outcome Measures

1. Synovial Fluid Drug Concentrations (pg/mL) by Time Point Pooled Across FX006 Cohorts and TCA IR in Synovial Fluid [Up to 20 Weeks]

   All baseline (pre-treatment) values and all post-baseline values recorded as below LLOQ (<50 pg/mL) were set to zero. Geometric mean summary statistics were computed on adjusted concentration values. One (1) was added to each concentration value observed. BLQ values for the computation of geometric mean are included in the summary with a value of 1 (0+1).

Secondary Outcome Measures

1. Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort [Up to 20 Weeks]

   All baseline (pre-treatment) values and all post-baseline values that are recorded as below LLOQ were set to zero for analysis and were included in the descriptive mean calculations. Values below LLOQ were not included in geometric mean calculations.

Other Outcome Measures

1. Plasma Pharmacokinetic Parameters for FX006 and TCA IR [Up to 20 Weeks]

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

• Willingness and ability to comply with the study procedures and visit schedules and ability to follow verbal and written instructions

• Symptoms associated with OA of the knee for ≥ 6 months prior to Screening (patient reported is acceptable)

• Currently meets American College of Rheumatology (ACR) Criteria (clinical and radiological) for OA

• Index knee pain for >15 days over the last month (as reported by the patient)

• Body mass index (BMI) ≤ 40 kg/m2

• Ambulatory and in good general health

Exclusion Criteria:

• Fibromyalgia, Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease

• History of infection in the index knee joint

• Clinical signs and symptoms of active knee infection or crystal disease of the index knee within 1 month of Screening

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

• Unstable joint within 12 months of Screening

• IA corticosteroid (investigational or marketed) in any joint within 6 months of Screening

• IA hyaluronic acid (investigational or marketed) in the index knee within 6 months of Screening

• Intravenous or Intramuscular corticosteroids (investigational or marketed) within 3 months of Screening

• Oral corticosteroids (investigational or marketed) within 1 month of Screening

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

• Any other IA investigational drug/biologic use within 6 months of Screening or 5 half-lives (whichever is longer)

• Prior use of FX006

• Women of child-bearing potential not using effective contraception or who are pregnant or nursing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Canoga Park	California	United States	91303
2		San Diego	California	United States	92103
3		Hialeah	Florida	United States	33012
4		Duncansville	Pennsylvania	United States	16635

Sponsors and Collaborators

• Flexion Therapeutics, Inc.

Investigators

• Study Director: Neil Bodick, MD, Flexion Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Osteoarthritis and Cartilage Journal Full Text Article

Publications

None provided.

• Responsible Party: Flexion Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02637323
• Other Study ID Numbers: FX006-2015-009
• First Posted: Dec 22, 2015
• Last Update Posted: Jan 12, 2018
• Last Verified: Dec 1, 2017

• Keywords provided by Flexion Therapeutics, Inc.: osteoarthritis; knee; pain; corticosteroid; intra-articular; injection
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; FX006; Triamcinolone diacetate

Study Results

Participant Flow

Recruitment Details	Patients were screened for study eligibility at four (4) study centers in the United States (US).
Pre-assignment Detail	Patients were enrolled sequentially with at least 10 patients per Cohort. Subjects were enrolled within 14 days of Screening.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	63 subjects received FX006 32 mg as a single 5 mL IA injection	18 subjects received TCA IR 40 mg as a single 1 mL IA injection
Period Title: Overall Study
STARTED	63	18
COMPLETED	61	17
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	FX006 32 mg	TCA IR 40 mg	Total
Arm/Group Description	Single 5 mL IA injection	Single 1 mL IA injection	Total of all reporting groups
Overall Participants	63	18	81
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.9 (8.16)	61.9 (7.68)	61 (8.16)
Sex: Female, Male (Count of Participants)
Female	32 50.8%	13 72.2%	45 55.6%
Male	31 49.2%	5 27.8%	36 44.4%

Outcome Measures

1. Primary Outcome

Title	Synovial Fluid Drug Concentrations (pg/mL) by Time Point Pooled Across FX006 Cohorts and TCA IR in Synovial Fluid
Description	All baseline (pre-treatment) values and all post-baseline values recorded as below LLOQ (<50 pg/mL) were set to zero. Geometric mean summary statistics were computed on adjusted concentration values. One (1) was added to each concentration value observed. BLQ values for the computation of geometric mean are included in the summary with a value of 1 (0+1).
Time Frame	Up to 20 Weeks

Outcome Measure Data

Analysis Population Description

All patients who received study drug and had synovial fluid obtained at the Synovial Fluid Visit and assayed for drug concentration levels.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	Single 5 mL IA injection	Single 1 mL IA injection
Measure Participants	17	8
Baseline (pre-treatment)	1.0	1.0
Week 1	231328.9
Week 6	3590.0	7.7
Week 12	290.6
Week 16	1.0
Week 20	1.0

2. Secondary Outcome

Title	Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort
Description	All baseline (pre-treatment) values and all post-baseline values that are recorded as below LLOQ were set to zero for analysis and were included in the descriptive mean calculations. Values below LLOQ were not included in geometric mean calculations.
Time Frame	Up to 20 Weeks

Outcome Measure Data

Analysis Population Description

All patients who received study drug and had at least one post-baseline plasma sample obtained and assayed for drug concentration levels.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	Single 5mL IA injection	Single 1 mL IA injection
Measure Participants	60	18
Day 1 - Hour 1	670.0	6968.8
Day 1 - Hour 2	736.5	8494.7
Day 1 - Hour 4	759.5	9628.8
Day 1 - Hour 6	747.1	9314.3
Day 1 - Hour 8	740.2	8421.3
Day 1 - Hour 10	720.7	7439.3
Day 1 - Hour 12	706.6	6678.7
Day 2 - Hour 24	836.4	4991.1
Week 1	600.9
Week 6	118.6	149.4
Week 12	53.7
Week 16	73.8
Week 20	108.2

3. Other Pre-specified Outcome

Title	Plasma Pharmacokinetic Parameters for FX006 and TCA IR
Time Frame	Up to 20 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse Events were collected following IA administration on Baseline/Day 1 up to 20 weeks.
Arm/Group Title	FX006 32 mg		TCA IR 40 mg
Arm/Group Description	Single 5 mL intra-articular injection FX006: Sustained Release Steroid		Commercially available triamcinolone acetonide, single 1 mL intra-articular injection TCA IR: Immediate Release Steroid
All Cause Mortality
	FX006 32 mg		TCA IR 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/63 (0%)		0/18 (0%)
Serious Adverse Events
	FX006 32 mg		TCA IR 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/63 (1.6%)		0/18 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	1/63 (1.6%)	1	0/18 (0%)	0
Other (Not Including Serious) Adverse Events
	FX006 32 mg		TCA IR 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/63 (11.1%)		2/18 (11.1%)
Infections and infestations
Nasopharyngitis	1/63 (1.6%)	1	0/18 (0%)	0
Injury, poisoning and procedural complications
Foot Fracture	1/63 (1.6%)	1	0/18 (0%)	1
Investigations
Weight Increased	1/63 (1.6%)	1	0/18 (0%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/63 (1.6%)	1	0/18 (0%)	1
Patellofemoral Pain Syndrome	1/63 (1.6%)	1	0/18 (0%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	1/63 (1.6%)	1	0/18 (0%)	1
Vascular disorders
Hypertension	2/63 (3.2%)	2	0/18 (0%)	2
Flushing	0/63 (0%)		2/18 (11.1%)	2

Limitations/Caveats

Subsequent to completion of clinical studies extensive testing was performed to assess the actual FX006 dose delivered. It was determined that the FX006 delivered dose to the patient from an FX006 40 mg vial is 32 mg.

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.