Study of FX006 vs Normal Saline in Patients With Osteoarthritis of the Knee

• Sponsor: Flexion Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02116972
• Collaborator: (none)
• Enrollment: 310
• Locations: 44
• Arms: 3
• Duration (Months): 19
• Patients Per Site: 7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study was to assess the magnitude and duration of pain relief of a single IA injection of 2 doses (16 and 32 mg) of FX006, an extended-release formulation of TCA, relative to normal saline (placebo control).

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis of the Knee	Drug: FX006 32 mg; Drug: Placebo; Drug: FX006 16 mg	Phase 2

Detailed Description

This was a double-blind, randomized, parallel group, dose-ranging, single-dose study. The study was conducted in male and female patients ≥40 years of age with OA of the knee.

Approximately 300 patients with OA of the knee were randomized, using a centralized randomization procedure, to 1 of 3 treatment groups (1:1:1) and treated with a single IA injection of:

• 16 mg FX006,

• 32 mg FX006, or

• normal saline (placebo).

Each patient was evaluated for a total of 24 weeks following a single IA injection. Following screening, safety and efficacy were evaluated at 7 out-patient visits (Days 1 [Baseline], Weeks 4, 8, 12, 16, 20, and 24).

The study was expected to enroll over approximately 6 to 7 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 310 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Randomized, Parallel Group, Dose-Ranging Study to Assess the Safety and Efficacy of FX006 for the Treatment of Pain in Patients With Osteoarthritis of the Knee
• Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FX006 16 mg Single 5 mL intra-articular (IA) injection Extended-release formulation	Drug: FX006 16 mg; Single 5 mL IA injection
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
Placebo Comparator: Placebo Normal Saline Single 5 mL intra-articular (IA) injection	Drug: Placebo; Single 5 mL IA injection; Other Names: Normal Saline

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 12 in the Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores for 32 mg FX006 Versus Placebo [Baseline and Week 12]

   The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates "no pain"and 10 indicates "pain as bad as you can imagine."

Secondary Outcome Measures

1. Change From Baseline to Week 12 for WOMAC C (Function Subscale) [Baseline and Week 12]

   The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.

2. Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC) [Baseline and Week 12]

   The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.

3. Change From Baseline to Week 16 and Then Week 20 and Then Week 24 in the Weekly Mean of the Average Daily (24-hour) Pain Intensity Scores [Baseline and Weeks 16, 20 and 24]

   The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine."

Other Outcome Measures

1. Percent of Responders According to Outcomes Measures in OMERACT-OARSI Strict Criteria [Weeks 4, 8 and 12]

   Outcome Measures in Rheumatoid Arthritis Clinical Trials - Osteoarthritis Research Society International. (OMERACT-OARSI) Responders are defined as participants with high improvement in pain or function.

2. Change From Baseline to Week 12 for WOMAC C (Function Subscale) [Baseline and Week 12]

   The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5- point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.

3. Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC) [Baseline and Week 12]

   The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.

4. Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores [Baseline and Up to Week 24]

   The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine."Weeks 12, 16, 20, and 24 are specified as the primary and secondary endpoints for the 32 mg group and the placebo group

5. Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function [Baseline and Weeks 4, 8, 16, 20 and 24 (Week 12 data is represented in the secondary outcome measure)]

   The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.

6. Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain [Baseline and Weeks 4, 8, 12, 16, 20 and 24]

   The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.

7. Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in PGIC [Baseline and Weeks 4, 8, 16, 20, and 24 (Week 12 data reported in secondary outcome measure)]

   The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.

8. Proportion of Patients Experiencing a >20%, 30% and 50% Decrease in Pain From Baseline in Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores at Week 12 [12 weeks]

   The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine."

9. Time to Onset of Pain Relief [Baseline up to 24 Weeks after administration of study treatment]

   Time to onset of pain relief in days is defined as the time from administration of study treatment to the first pain assessment showing >30% improvement from the weekly average daily pain score at baseline.

Eligibility Criteria

Criteria

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

Main Inclusion Criteria:

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

• Male or female >=40 years of age

• Has documented diagnosis of OA of the index knee made at least 6 months prior to Screening

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

• Kellgren-Lawrence (K-L) Grade 2 or 3 in the index knee per Screening X-ray

• Qualifying mean score on the 24-h average pain score (0-10 numeric rating scale)

• Body mass index (BMI) ≤ 40 kg/m2

• Willingness to abstain from use of restricted medications

Main Exclusion Criteria:

• Ipsilateral hip OA

• Fibromyalgia, chronic pain syndrome or other concurrent medical or arthritic conditions which could interfere with the evaluation of the index knee

• History of Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, sarcoidosis or amyloidosis

• History of arthritides due to crystals (e.g., gout, pseudogout)

• History or clinical signs and symptoms of infection in the index joint

• Knee pain that is not clinically attributable to OA of the knee (e.g., radicular low back pain and hip pain that is referred to the knee that could cause misclassification)

• Pain in any other area of the lower extremities or back that is equal to or greater than the index knee pain

• IA corticosteroid (investigational or marketed) in any joint within 3 months of Screening

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

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

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

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

• Any other IA investigational drug/biologic within 6 months of Screening

• 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		Anniston	Alabama	United States	36207
2		Birmingham	Alabama	United States	35216
3		Mobile	Alabama	United States	36608
4		Phoenix	Arizona	United States	85023
5		Tucson	Arizona	United States	85704
6		Hot Springs	Arkansas	United States	71913
7		Anaheim	California	United States	92801
8		Canoga Park	California	United States	91303
9		El Cajon	California	United States	92020
10		Los Angeles	California	United States	90036
11		North Hollywood	California	United States	91606
12		San Diego	California	United States	92103
13		Stamford	Connecticut	United States	06905
14		DeLand	Florida	United States	32720
15		Fort Lauderdale	Florida	United States	33316
16		Orlando	Florida	United States	32825
17		Pinellas Park	Florida	United States	33781
18		Tampa	Florida	United States	33613
19		Marietta	Georgia	United States	30060
20		Evansville	Indiana	United States	47713
21		Paducah	Kentucky	United States	42003
22		Wheaton	Maryland	United States	20902
23		New Bedford	Massachusetts	United States	02740
24		Troy	Michigan	United States	48085
25		Kansas City	Missouri	United States	64114
26		Las Vegas	Nevada	United States	89106
27		Albuquerque	New Mexico	United States	87102
28		New York	New York	United States	10018
29		Rochester	New York	United States	14609
30		Raleigh	North Carolina	United States	27612
31		Oklahoma City	Oklahoma	United States	73112
32		Altoona	Pennsylvania	United States	16602
33		Duncansville	Pennsylvania	United States	16635
34		Mount Pleasant	South Carolina	United States	29464
35		Dallas	Texas	United States	75231
36		Houston	Texas	United States	77055
37		San Antonio	Texas	United States	78258
38		Victoria	Texas	United States	77901
39		Danville	Virginia	United States	24541
40		Kitchener	Ontario	Canada
41		Sarnia	Ontario	Canada
42		Toronto	Ontario	Canada
43		Windsor	Ontario	Canada
44		Quebec		Canada

Sponsors and Collaborators

• Flexion Therapeutics, Inc.

Investigators

• Study Director: Neil Bodick, MD, Flexion Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Flexion Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02116972
• Other Study ID Numbers: FX006-2014-006
• First Posted: Apr 17, 2014
• Last Update Posted: Mar 20, 2018
• Last Verified: Mar 1, 2018

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

Study Results

Participant Flow

Recruitment Details	Patients were screened for study eligibility at 48 study centers in the United States (US) and Canada. Enrollment took approximately 7 months.
Pre-assignment Detail	Subjects were screened within 21 days of being randomized

Arm/Group Title	FX006 16 mg	FX006 32 mg	Placebo
Arm/Group Description	102 subjects received FX006 16 mg a single 5 mL IA injection	104 subjects received FX006 32 mg a single 5 mL IA injection	100 subjects received normal saline as a single 5 mL IA injection
Period Title: Overall Study
STARTED	102	104	104
COMPLETED	83	87	85
NOT COMPLETED	19	17	19

Baseline Characteristics

Arm/Group Title	FX006 16 mg	FX006 32 mg	Normal Saline	Total
Arm/Group Description	Single intra-articular injection FX006: Single intra-articular injection	Single intra-articular injection FX006: Single intra-articular injection	Single intra-articular injection Normal saline: Single intra-articular injection	Total of all reporting groups
Overall Participants	102	104	100	306
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.2 (8.34)	58.7 (8.06)	59.7 (8.23)	58.8 (8.20)
Sex: Female, Male (Count of Participants)
Female	62 60.8%	51 49%	61 61%	174 56.9%
Male	40 39.2%	53 51%	39 39%	132 43.1%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 12 in the Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores for 32 mg FX006 Versus Placebo
Description	The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates "no pain"and 10 indicates "pain as bad as you can imagine."
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Randomized patients who received study drug assigned to the FX006 32 mg arm and the placebo arm

Arm/Group Title	FX006 32 mg	Placebo
Arm/Group Description	FX006: Single 5 mL IA injection	Normal Saline: Single 5 mL IA injection
Measure Participants	104	100
Least Squares Mean (Standard Error) [units on a scale]	-3.08 (0.229)	-2.50 (0.238)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FX006 32 mg, Placebo
	Comments	The step-down testing procedure to control for multiplicity would be voided if the primary endpoint is not met and analyses proceeded for exploratory purposes.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0821
	Comments
	Method	Logitudinal mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.58
	Confidence Interval	(2-Sided) 95%; -1.22 to 0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to Week 12 for WOMAC C (Function Subscale)
Description	The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FX006 32 mg	Placebo
Arm/Group Description	FX006: Single 5 mL IA injection	Normal Saline: Single 5 mL IA injection
Measure Participants	104	100
Least Squares Mean (Standard Error) [units on a scale]	-1.01 (0.083)	-0.79 (0.087)

3. Secondary Outcome

Title	Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC)
Description	The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FX006 32 mg	Placebo
Arm/Group Description	FX006: Single 5 mL IA injection	Normal Saline: Single 5 mL IA injection
Measure Participants	104	100
Least Squares Mean (Standard Error) [units on a scale]	2.6 (0.14)	2.7 (0.14)

4. Secondary Outcome

Title	Change From Baseline to Week 16 and Then Week 20 and Then Week 24 in the Weekly Mean of the Average Daily (24-hour) Pain Intensity Scores
Description	The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine."
Time Frame	Baseline and Weeks 16, 20 and 24

Outcome Measure Data

Analysis Population Description

Randomized patients who received study drug.

Arm/Group Title	FX006 32 mg	Placebo
Arm/Group Description	FX006: Single 5 mL IA injection	Normal Saline: Single 5 mL IA injection
Measure Participants	104	100
Week 16	-2.83 (0.2224)	-2.46 (0.234)
Week 20	-2.81 (0.233)	-2.34 (0.244)
Week 24	-2.51 (0.241)	-2.24 (0.252)

5. Other Pre-specified Outcome

Title	Percent of Responders According to Outcomes Measures in OMERACT-OARSI Strict Criteria
Description	Outcome Measures in Rheumatoid Arthritis Clinical Trials - Osteoarthritis Research Society International. (OMERACT-OARSI) Responders are defined as participants with high improvement in pain or function.
Time Frame	Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

Percent of responders according to Outcomes Measures in OMERACT-OARSI strict criteria for patients assigned to FX006 16 mg arm was not a pre-specified Secondary Outcome and therefore not reported.

Arm/Group Title	FX006 32 mg	Placebo
Arm/Group Description	FX006: Single 5 mL IA injection	Normal Saline: Single 5 mL IA injection
Measure Participants	104	100
Week 4	75 73.5%	51 49%
Week 8	73 71.6%	58 55.8%
Week 12	70 68.6%	57 54.8%

6. Other Pre-specified Outcome

Title	Change From Baseline to Week 12 for WOMAC C (Function Subscale)
Description	The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5- point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FX006 16 mg	Placebo
Arm/Group Description	FX006: Single 5 mL IA injection	Normal Saline: Single 5 mL IA injection
Measure Participants	102	100
Least Squares Mean (Standard Error) [units on a scale]	-0.83 (0.085)	-0.79 (0.087)

7. Other Pre-specified Outcome

Title	Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC)
Description	The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FX006 16 mg	Placebo
Arm/Group Description	FX006: Single 5 mL IA injection	Normal Saline: Single 5 mL IA injection
Measure Participants	102	100
Least Squares Mean (Standard Error) [units on a scale]	2.5 (0.14)	2.7 (0.14)

8. Other Pre-specified Outcome

Title	Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores
Description	The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine."Weeks 12, 16, 20, and 24 are specified as the primary and secondary endpoints for the 32 mg group and the placebo group
Time Frame	Baseline and Up to Week 24

Outcome Measure Data

Analysis Population Description

Randomized patients who received study drug.

Arm/Group Title	FX006 16 mg	FX006 32 mg	Placebo
Arm/Group Description	FX006: Single 5 mL IA injection	FX006: Single 5 mL IA injection	Normal Saline: Single 5 mL IA injection
Measure Participants	102	104	100
Week 1	-2.04 (0.177)	-1.96 (0.175)	-1.24 (0.178)
Week 2	-2.88 (0.218)	-2.75 (0.216)	-1.65 (0.220)
Week 3	-2.90 (0.228)	-2.91 (0.226)	-1.74 (0.231)
Week 4	-3.05 (0.228)	-3.20 (0.226)	-1.84 (0.232)
Week 5	-3.28 (0.222)	-3.39 (0.219)	-2.05 (0.225)
Week 6	-3.27 (0.225)	-3.29 (0.222)	-2.20 (0.229)
Week 7	-3.14 (0.233)	-3.13 (0.230)	-2.28 (0.237)
Week 8	-3.08 (0.237)	-3.04 (0.234)	-2.33 (0.242)
Week 9	-3.09 (0.233)	-3.24 (0.229)	-2.39 (0.237)
Week 10	-2.88 (0.229)	-3.17 (0.224)	-2.44 (0.233)
Week 11	-2.78 (0.234)	-3.18 (0.229)	-2.48 (0.238)
Week 12	-2.59 (0.234)	-3.08 (0.229)	-2.50 (0.238)
Week 13	-2.68 (0.234)	-3.12 (0.229)	-2.43 (0.239)
Week 14	-2.38 (0.235)	-2.83 (0.229)	-2.48 (0.239)
Week 15	-2.38 (0.225)	-2.91 (0.219)	-2.44 (0.229)
Week 16	-2.30 (0.231)	-2.83 (0.224)	-2.46 (0.234)
Week 17	-2.32 (0.237)	-2.71 (0.229)	-2.41 (0.240)
Week 18	-2.32 (0.240)	-2.73 (0.232)	-2.34 (0.242)
Week 19	-2.27 (0.241)	-2.76 (0.233)	-2.28 (0.243)
Week 20	-2.27 (0.241)	-2.81 (0.233)	-2.34 (0.244)
Week 21	-2.21 (0.246)	-2.71 (0.237)	-2.38 (0.248)
Week 22	-2.41 (0.249)	-2.53 (0.240)	-2.30 (0.251)
Week 23	-2.33 (0.258)	-2.40 (0.249)	-2.25 (0.260)
Week 24	-2.38 (0.249)	-2.51 (0.241)	-2.24 (0.252)

9. Other Pre-specified Outcome

Title	Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function
Description	The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time Frame	Baseline and Weeks 4, 8, 16, 20 and 24 (Week 12 data is represented in the secondary outcome measure)

Outcome Measure Data

Analysis Population Description

Change from baseline to each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function for patients assigned to FX006 16 mg arm was not a pre-specified Secondary Outcome and therefore not reported

Arm/Group Title	FX006 32 mg	Placebo
Arm/Group Description	FX006: Single 5 mL IA injection	Normal Saline: Single 5 mL IA injection
Measure Participants	104	100
Week 4	-1.16 (0.079)	-0.66 (0.082)
Week 8	-1.09 (0.082)	-0.74 (0.085)
Week 16	-0.94 (0.083)	-0.84 (0.086)
Week 20	-0.87 (0.082)	-0.84 (0.085)
Week 24	-0.89 (0.083)	-0.80 (0.086)

10. Other Pre-specified Outcome

Title	Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain
Description	The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time Frame	Baseline and Weeks 4, 8, 12, 16, 20 and 24

Outcome Measure Data

Analysis Population Description

Change from baseline to each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A pain for patients assigned to FX006 16 mg arm was not a pre-specified Secondary Outcome and therefore not reported.

Arm/Group Title	FX006 32 mg	Placebo
Arm/Group Description	FX006: Single 5 mL IA injection	Normal Saline: Single 5 mL IA injection
Measure Participants	104	100
Week 4	-1.11 (0.080)	-0.64 (0.082)
Week 8	-1.09 (0.083)	-0.71 (0.087)
Week 12	-0.98 (0.080)	-0.81 (0.083)
Week 16	-0.95 (0.083)	-0.80 (0.087)
Week 20	-0.89 (0.083)	-0.84 (0.086)
Week 24	-0.91 (0.084)	-0.78 (0.086)

11. Other Pre-specified Outcome

Title	Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in PGIC
Description	The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.
Time Frame	Baseline and Weeks 4, 8, 16, 20, and 24 (Week 12 data reported in secondary outcome measure)

Outcome Measure Data

Analysis Population Description

Change from baseline to each of Weeks 4, 8, 16, 20, and 24 in PGIC for patients assigned to FX006 16 mg arm was not a pre-specified Secondary Outcome and therefore not reported.

Arm/Group Title	FX006 32 mg	Placebo
Arm/Group Description	FX006: Single 5 mL IA injection	Normal Saline: Single 5 mL IA injection
Measure Participants	104	100
Week 4	2.2 (0.13)	3.0 (0.13)
Week 8	2.4 (0.14)	2.8 (0.14)
Week 16	2.8 (0.16)	2.7 (0.16)
Week 20	2.9 (0.15)	2.8 (0.16)
Week 24	2.7 (0.16)	3.1 (0.16)

12. Other Pre-specified Outcome

Title	Proportion of Patients Experiencing a >20%, 30% and 50% Decrease in Pain From Baseline in Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores at Week 12
Description	The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine."
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Other Pre-specified Outcome

Title	Time to Onset of Pain Relief
Description	Time to onset of pain relief in days is defined as the time from administration of study treatment to the first pain assessment showing >30% improvement from the weekly average daily pain score at baseline.
Time Frame	Baseline up to 24 Weeks after administration of study treatment

Outcome Measure Data

Analysis Population Description

Time to onset of pain relief for patients assigned to FX006 16 mg arm was not a pre-specified Secondary Outcome and therefore not reported.

Arm/Group Title	FX006 32 mg	Placebo
Arm/Group Description	FX006: Single 5 mL IA injection	Normal Saline: Single 5 mL IA injection
Measure Participants	104	100
Median (95% Confidence Interval) [days]	4	8

Adverse Events

Time Frame	Adverse Events were collected following IA administration through the final study visit.
Adverse Event Reporting Description	A total of 310 subjects were randomized to a treatment assignment but only 306 enrolled subjects received their randomized treatment. Four (4) subjects randomized to placebo arm were were not treated.
Arm/Group Title	FX006 16 mg		FX006 32 mg		Placebo
Arm/Group Description	Single 5 mL IA injection		Single 5 mL IA injection		Single 5 mL IA injection
All Cause Mortality
	FX006 16 mg		FX006 32 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/102 (0%)		0/104 (0%)		0/100 (0%)
Serious Adverse Events
	FX006 16 mg		FX006 32 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/102 (1%)		3/104 (2.9%)		0/100 (0%)
Cardiac disorders
Myocardial Infarction	0/102 (0%)	0	1/104 (1%)	1	0/100 (0%)	0
Injury, poisoning and procedural complications
Femur Fracture	1/102 (1%)	1	0/104 (0%)	0	0/100 (0%)	0
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/102 (0%)	0	1/104 (1%)	1	0/100 (0%)	0
Rheumatoid Arthritis	0/102 (0%)	0	1/104 (1%)	1	0/100 (0%)	0
Other (Not Including Serious) Adverse Events
	FX006 16 mg		FX006 32 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/102 (13.7%)		13/104 (12.5%)		21/100 (21%)
Musculoskeletal and connective tissue disorders
Arthralgia	10/102 (9.8%)	10	8/104 (7.7%)	8	16/100 (16%)	16
Joint Swelling	4/102 (3.9%)	4	5/104 (4.8%)	5	5/100 (5%)	5

Limitations/Caveats

Subsequent to completion of clinical studies extensive testing was performed to assess the actual dose delivered. It was determined that the FX006 delivered dose to the patient from an FX006 40 mg vial is 32 mg and from FX006 20 mg vial is 16 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.