Study to Evaluate the Efficacy and Safety of FX006 in Patients With Hip Osteoarthritis

• Sponsor: Flexion Therapeutics, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03793010
• Collaborator: (none)
• Enrollment: 70
• Locations: 32
• Arms: 2
• Actual Duration (Months): 7.8
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a two-part, multi-center, randomized, double-blind, placebo-controlled, parallel-group study in patients with hip OA. Approximately 70 patients will be enrolled in Part I and approximately 440 patients will be enrolled in Part II of the study. In each part, patients will be randomized to one of two treatment groups (1:1) and treated with a single IA injection of either 32 mg FX006 or normal saline.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis, Hip	Drug: FX006; Drug: Normal saline	Phase 3

Detailed Description

This is a two-part, multi-center, randomized, double-blind, placebo-controlled, parallel-group study in patients with hip OA. Approximately 70 patients will be enrolled in Part I and approximately 440 patients will be enrolled in Part II of the study. In each part, patients will be randomized to one of two treatment groups (1:1) and treated with a single IA injection of either 32 mg FX006 or normal saline.

FX006 or saline placebo will be administered as a single IA injection with a 12-week follow-up period in the double-blind phase.

Patients participating in Part I of the study will be treated with a single IA injection of either 32 mg FX006 or normal saline and will return for follow up visits at Weeks 12, 16, 20, and 24. The patients will be discontinued at the time of notification by the Investigator.

Patients participating in Part II of the study will be treated with a single IA injection of either 32 mg FX006 or normal saline and will return for follow up visits at Weeks 12, 16, 20, and 24.

Patients participating in Part II of the study that are not clinically indicated for a second injection at Week 12 will return to the clinic at Weeks 16, 20, and 24 and will receive an open-label injection of FX006 at the first evaluation where the patient has been determined to meet all criteria. Patients will then return for follow-up visits every 4 weeks for 12 weeks post second injection and will complete the study 12 weeks post second injection (e.g., Week 24, 28, 32, or 36 depending on when the patient receives the open-label injection).

Patients participating in Part II of the study who are not eligible for a second injection after evaluation at Weeks 12, 16, 20, and 24 will complete the study at the Week 24 visit and complete the End of Study (EOS) assessments.

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, Double-blind, Placebo-controlled, Parallel-groupRandomized, Double-blind, Placebo-controlled, Parallel-group
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of FX006 in Patients With Hip Osteoarthritis
• Actual Study Start Date: Dec 12, 2018
• Actual Primary Completion Date: Aug 7, 2019
• Actual Study Completion Date: Aug 7, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FX006 FX006 32mg	Drug: FX006; Single Intra-articular injection
Placebo Comparator: Normal Saline Normal Saline	Drug: Normal saline; Single Intra-articular injection

Outcome Measures

Primary Outcome Measures

1. Change in WOMAC A (Pain) Score at Week 12 [Baseline and Week 12]

   The change from baseline on the average Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A (pain) score at Week 12. The average WOMAC A score is calculated by taking the average of five questions with a range from 0 (no pain) to 10 (extreme pain).

Secondary Outcome Measures

1. Change in WOMAC C (Function) Score at Week 12 [Baseline and Week 12]

   Change from Baseline on the WOMAC C (function) score at Week 12. The average WOMAC C score is calculated by taking the average of seventeen questions with a range from 0 (no difficulty) to 10 (extreme difficulty).

2. PGIC Score at Week 12 [12 Weeks]

   PGIC (Patient Global Impression of Change) at Week 12. The PGIC score has a range from 1(very much improved) to 7 (very much worse) and indicates the overall status of the patient since baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

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

• Patients 40 to 80 years of age, inclusive, on the day of randomization (Day 1)

• Body Mass Index (BMI) ≤ 40 kg/m2

• Symptoms associated with OA of the index hip for ≥ 3 months prior to Screening visit

• Currently meet the American College of Radiology (ACR) Criteria (clinical and radiological) for OA of the index hip

• Kellgren-Lawrence (KL) Grade 2 or 3 in the index hip as confirmed by X-ray during Screening visit (centrally read)

• Qualifying mean score on the WOMAC A and C (0-10 NRS scale)

• Agree to maintain the similar activity level throughout the study

• Willingness to abstain from use of restricted medications

Exclusion Criteria:

• Patients who cannot washout of prohibited medications

• Diagnosed as secondary OA in the index hip including but not limited to articular fracture, major dysplasia or congenital abnormality, osteochondritis dissecans, acromegaly, ochronosis, hemochromatosis, Wilson's disease, or primary osteochondromatosis, etc.

• Ipsilateral chronic knee pain

• Sciatica

• Atrophic osteoarthritis, femoral head necrosis and/or collapse, or subchondral bone insufficiency fracture in the index hip joint determined via central reading

• Current or history of infection in the index hip (e.g. osteomyelitis) or current skin infection at injection site

• Trauma or surgeries (e.g., arthroscopy, knee surgery) of lower limbs within 52 weeks with sequelae, etc.

• History or current evidence of reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease, systemic lupus erythematosus or other autoimmune diseases

• Any planned surgeries in the lower limbs during the study period, or any other surgery during the study period that would require use of a restricted medication

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

• Planned/anticipated surgery of the index hip or any other surgery that would require use of a restricted medication during the study period

• IA corticosteroid of any joint within 3 months of Screening visit (investigational or marketed, including FX006)

• IA treatment of index hip with any of the following agents within 6 months of Screening: any biologic agent or hyaluronic acid (investigational or marketed)

• IV or IM 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 visit

• Planned or expected changes to lifestyle with regard to physical activity, physical therapy, acupuncture, transcutaneous electrical nerve stimulation (TENS), or bracing within 1 month prior to Screening and changes throughout the duration of the study

• Women of child-bearing potential (not surgically sterile or post-menopausal for at least 1 year as documented in medical history) not using a highly effective method or who are pregnant or nursing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Research Center	Phoenix	Arizona	United States	85053
2	Noble Clinical Research	Tucson	Arizona	United States	85704
3	Hope Clinical Research	Canoga Park	California	United States	91303
4	TriWest Research Associates, LLC	El Cajon	California	United States	92020
5	BioSolutions Clinical Research Center	La Mesa	California	United States	91942
6	Artemis Institute for Clinical Research	San Diego	California	United States	92103
7	Mountain View Clinical Research, Inc.	Denver	Colorado	United States	80209
8	Chase Medical Research, LLC	Waterbury	Connecticut	United States	06708
9	Tampa Bay Medical Research	Clearwater	Florida	United States	33761
10	Florida Research Associates, LLC	DeLand	Florida	United States	32720
11	Advanced Research for Health Improvement	Naples	Florida	United States	34102
12	Medallion Clinical Research Institute, LLC	Naples	Florida	United States	34102
13	Oviedo Medical Research	Oviedo	Florida	United States	32765
14	Progressive Medical Research	Port Orange	Florida	United States	32127
15	Precision Clinical Research, LLC	Sunrise	Florida	United States	33351
16	National Pain Research Institute	Winter Park	Florida	United States	32789
17	Better Health Clinical Research, Inc	Newnan	Georgia	United States	30265
18	Injury Care Research, LLC	Boise	Idaho	United States	83713
19	Northwestern University Feinberg School of Medicine	Chicago	Illinois	United States	60611
20	Heartland Research Associates	Newton	Kansas	United States	67114
21	Excel Clinical Research	Las Vegas	Nevada	United States	89109
22	Drug Trials America	Hartsdale	New York	United States	10530
23	M3 Wake Research, Inc.	Raleigh	North Carolina	United States	27612
24	PMG Research of Wilmington	Wilmington	North Carolina	United States	28401
25	University Orthopedics Center	Altoona	Pennsylvania	United States	16602
26	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
27	Clinical Trials of South Carolina	Charleston	South Carolina	United States	29406
28	Coastal Carolina Research Center	Charleston	South Carolina	United States	29406
29	Wasatch Clinical Research, LLC	Salt Lake City	Utah	United States	84107
30	Charlottesville Medical Research	Charlottesville	Virginia	United States	22911
31	Spectrum Medical, Inc.	Danville	Virginia	United States	24541
32	Northwest Clinical Research Center	Bellevue	Washington	United States	98007

Sponsors and Collaborators

• Flexion Therapeutics, Inc.

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Jul 31, 2019
• Statistical Analysis Plan - Sep 5, 2019

More Information

Publications

None provided.

• Responsible Party: Flexion Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03793010
• Other Study ID Numbers: FX006-2018-015
• First Posted: Jan 4, 2019
• Last Update Posted: Jan 21, 2022
• Last Verified: Jan 1, 2022

• 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; Hip; Pain; Intra-articular; Injection
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Hip; FX006

Study Results

Participant Flow

Recruitment Details	The recruitment period for this study was from December 2018 until August 2019. The patients were enrolled at medical clinics.

Arm/Group Title	FX006	Normal Saline
Arm/Group Description	FX006 32mg FX006: Single Intra-articular injection	Normal Saline Normal saline: Single Intra-articular injection
Period Title: Overall Study
STARTED	35	35
Randomized But Not Dosed	2	0
COMPLETED	7	8
NOT COMPLETED	28	27

Baseline Characteristics

Arm/Group Title	FX006	Normal Saline	Total
Arm/Group Description	FX006 32mg FX006: Single Intra-articular injection	Normal Saline Normal saline: Single Intra-articular injection	Total of all reporting groups
Overall Participants	33	35	68
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.6 (9.45)	61.8 (7.99)	60.7 (8.73)
Sex: Female, Male (Count of Participants)
Female	20 60.6%	21 60%	41 60.3%
Male	13 39.4%	14 40%	27 39.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 12.1%	4 11.4%	8 11.8%
Not Hispanic or Latino	28 84.8%	31 88.6%	59 86.8%
Unknown or Not Reported	1 3%	0 0%	1 1.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 3%	0 0%	1 1.5%
Asian	0 0%	1 2.9%	1 1.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	8 24.2%	8 22.9%	16 23.5%
White	24 72.7%	26 74.3%	50 73.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Number) [Number]
United States	33 100%	35 100%	68 100%
Body Mass Index (BMI) (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	30.50 (5.679)	31.29 (5.775)	30.91 (5.699)

Outcome Measures

1. Primary Outcome

Title	Change in WOMAC A (Pain) Score at Week 12
Description	The change from baseline on the average Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A (pain) score at Week 12. The average WOMAC A score is calculated by taking the average of five questions with a range from 0 (no pain) to 10 (extreme pain).
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

All patients who received a full dose of study drug assigned to the FX006 32 mg arm and the placebo arm were included in the analysis. 68 total patients were included in the safety analysis. 55 of 68 patients had Week 12 assessments and are included in the primary and secondary outcomes analysis.

Arm/Group Title	FX006	Normal Saline
Arm/Group Description	FX006 32mg FX006: Single Intra-articular injection	Normal Saline Normal saline: Single Intra-articular injection
Measure Participants	24	31
Least Squares Mean (95% Confidence Interval) [score on a scale]	-1.85	-2.16

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FX006, Normal Saline
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.31
	Confidence Interval	(2-Sided) 95%; -1.20 to 1.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in WOMAC C (Function) Score at Week 12
Description	Change from Baseline on the WOMAC C (function) score at Week 12. The average WOMAC C score is calculated by taking the average of seventeen questions with a range from 0 (no difficulty) to 10 (extreme difficulty).
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

All patients who received a full dose of study drug assigned to the FX006 32 mg arm and the placebo arm were included in the analysis. 68 total patients were included in the safety population. 55 of 68 patients had week 12 assessments and are included in the primary and secondary outcomes analysis.

Arm/Group Title	FX006	Normal Saline
Arm/Group Description	FX006 32mg FX006: Single Intra-articular injection	Normal Saline Normal saline: Single Intra-articular injection
Measure Participants	24	31
Least Squares Mean (95% Confidence Interval) [score on a scale]	-1.56	-2.16

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FX006, Normal Saline
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95%; -1.05 to 2.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	PGIC Score at Week 12
Description	PGIC (Patient Global Impression of Change) at Week 12. The PGIC score has a range from 1(very much improved) to 7 (very much worse) and indicates the overall status of the patient since baseline.
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

All patients who received a full dose of study drug assigned to the FX006 32 mg arm and the placebo arm were included in the analysis. 68 total patients were included in the safety population. 55 of 68 patients had week 12 assessments and are included in the primary and secondary outcomes analysis.

Arm/Group Title	FX006	Normal Saline
Arm/Group Description	FX006 32mg FX006: Single Intra-articular injection	Normal Saline Normal saline: Single Intra-articular injection
Measure Participants	24	31
Least Squares Mean (95% Confidence Interval) [score on a scale]	3.4	3.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FX006, Normal Saline
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.0
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse event data was collected for FX006 32 mg and Placebo from Baseline to Last Visit at Week 24.
Arm/Group Title	FX006		Normal Saline
Arm/Group Description	FX006 32mg FX006: Single Intra-articular injection		Normal Saline Normal saline: Single Intra-articular injection
All Cause Mortality
	FX006		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/35 (0%)
Serious Adverse Events
	FX006		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/35 (0%)
Other (Not Including Serious) Adverse Events
	FX006		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/33 (63.6%)		14/35 (40%)
Blood and lymphatic system disorders
Thrombocytopenia	1/33 (3%)		0/35 (0%)
Gastrointestinal disorders
Dry Mouth	1/33 (3%)		0/35 (0%)
Dyspepsia	0/33 (0%)		1/35 (2.9%)
Dysphagia	2/33 (6.1%)		0/35 (0%)
Peptic Ulcer	0/33 (0%)		1/35 (2.9%)
General disorders
Adhesion	0/33 (0%)		1/35 (2.9%)
Chest Discomfort	1/33 (3%)		0/35 (0%)
Thirst	0/33 (0%)		1/35 (2.9%)
Hepatobiliary disorders
Cholelithiasis	0/33 (0%)		1/35 (2.9%)
Immune system disorders
Hypersensitivity	0/33 (0%)		1/35 (2.9%)
Infections and infestations
Bronchitis	1/33 (3%)		1/35 (2.9%)
Gastroenteritis Viral	1/33 (3%)		0/35 (0%)
Hordeolum	0/33 (0%)		1/35 (2.9%)
Influenza	0/33 (0%)		1/35 (2.9%)
Pharyngitis	0/33 (0%)		1/35 (2.9%)
Sinusitis	0/33 (0%)		1/35 (2.9%)
Upper Respiratory Tract Infection	0/33 (0%)		1/35 (2.9%)
Injury, poisoning and procedural complications
Arthropod Bite	1/33 (3%)		0/35 (0%)
Fall	0/33 (0%)		1/35 (2.9%)
Repetitive Strain Injury	1/33 (3%)		0/35 (0%)
Investigations
Blood Glucose Increased	1/33 (3%)		0/35 (0%)
Blood Pressure Diastolic Increased	1/33 (3%)		1/35 (2.9%)
Blood Pressure Increased	2/33 (6.1%)		1/35 (2.9%)
Hepatic Enzyme Increased	1/33 (3%)		0/35 (0%)
Weight Increased	2/33 (6.1%)		0/35 (0%)
White Blood Cell Count Decreased	1/33 (3%)		0/35 (0%)
Metabolism and nutrition disorders
Decreased Apetite	0/33 (0%)		1/35 (2.9%)
Diabetes Mellitus	1/33 (3%)		0/35 (0%)
Hyperglycemia	0/33 (0%)		1/35 (2.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/33 (24.2%)		1/35 (2.9%)
Back Pain	1/33 (3%)		1/35 (2.9%)
Intervertebral Disc Protrusion	0/33 (0%)		1/35 (2.9%)
Musculoskeletal Chest Pain	0/33 (0%)		1/35 (2.9%)
Nervous system disorders
Headache	0/33 (0%)		1/35 (2.9%)
Lumbar Radiculopathy	2/33 (6.1%)		0/35 (0%)
Renal and urinary disorders
Renal Cyst	0/33 (0%)		1/35 (2.9%)
Respiratory, thoracic and mediastinal disorders
Cough	1/33 (3%)		0/35 (0%)
Skin and subcutaneous tissue disorders
Intertrigo	1/33 (3%)		0/35 (0%)
Rash	0/33 (0%)		1/35 (2.9%)
Vascular disorders
Hot Flush	0/33 (0%)		1/35 (2.9%)
Hypertension	0/33 (0%)		1/35 (2.9%)

Limitations/Caveats

This study was terminated early by the Sponsor due to occurrences of incomplete study drug administration. Only 15% of the planned study population had enrolled and no statistical evaluations reported due to insufficient sample size.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.