Study to Evaluate the Effect of FX006 on Synovial Inflammation in Patients With OA of the Knee

• Sponsor: Flexion Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03529942
• Collaborator: (none)
• Enrollment: 129
• Locations: 10
• Arm: 1
• Actual Duration (Months): 22.5
• Patients Per Site: 12.9
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This is an open-label study assessing the effect of the administration of a single intra-articular (IA) injection of FX006 32 mg on synovial volume in patients with osteoarthritis (OA) of the knee.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis, Knee	Drug: FX006 32 mg	Phase 3

Detailed Description

This is an open-label study assessing the effect of the administration of a single intra-articular (IA) injection of FX006 32 mg on synovial volume in patients with osteoarthritis (OA) of the knee. The study will be conducted in male and female patients who are ≥ 40 years of age.

Eligible patients who provide written consent and meet all entry criteria will undergo initial ultrasound examination and MRI with contrast of the index knee, and then receive a single IA injection of FX006 administered to the index knee at Baseline/Day 1. Patients will return to the clinic at Weeks 6 and 24 for an MRI with contrast of the index knee and other assessments. Patients must also have a blood sample drawn for Estimated Glomerular Filtration Rate (eGFR) testing within 30 days prior to the scheduled MRIs. In addition, a patient questionnaire will be administered and adverse events (AEs) and concomitant medication updates will be collected via telephone at Weeks 12 and 18.

Study Design

• Study Type: Interventional
• Actual Enrollment: 129 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Study to Evaluate the Effect of the Administration of FX006 on Synovial Inflammation in Patients With Osteoarthritis of the Knee
• Actual Study Start Date: Apr 24, 2018
• Actual Primary Completion Date: Nov 8, 2019
• Actual Study Completion Date: Mar 9, 2020

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

Outcome Measures

Primary Outcome Measures

1. Mean Standardized Change in Synovial Volume (SV) at 6 Weeks [Baseline to Week 6]

   Synovial volume (mm^3) as measured by MRI and read by a central imaging vendor. Standardization was performed by dividing the model-derived least squares means and corresponding confidence intervals by the adjusted standard deviation (SD). Therefore, the mean standardized change represents the change in synovial volume expressed in standard deviation units.

Secondary Outcome Measures

1. Mean Absolute Change in Synovial Volume at 6 Weeks [Baseline to Week 6]

   Mean absolute change from baseline at 6 weeks in synovial volume (mm^3) as measured by MRI and read by a central imaging vendor. The least squares mean changes are estimated using a mixed effects model for repeated measures with fixed effects for study time point, study site, baseline score and baseline femur bone volume (mm^3) and a random effect for patient.

2. Mean Standardized Change in Synovial Volume (SV) at 24 Weeks [Baseline to Week 24]

   Synovial volume (mm^3) as measured by MRI and read by a central imaging vendor. Standardization was performed by dividing the model-derived least squares means and corresponding confidence intervals by the adjusted standard deviation (SD). Therefore, the mean standardized change represents the change in synovial volume expressed in standard deviation units.

3. Mean Absolute Change in Synovial Volume at 24 Weeks [Baseline to Week 24]

   Mean absolute change (mm^3) from baseline at 24 weeks in synovial volume (mm^3) as measured by MRI and read by a central imaging vendor. The least squares mean changes are estimated using a mixed effects model for repeated measures with fixed effects for study time point, study site, baseline score and baseline femur bone volume (mm^3) and a random effect for patient.

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 ≥ 40 years of age

• Body mass index (BMI) ≤ 40 kg/m^2

• 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 medications during the study

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

• 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 based on X-ray performed during Screening (centrally read)

Exclusion Criteria:

• Any inflammatory arthritis including reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, gout or secondary OA from gout

• History of infection or crystal disease in the index knee joint

• Unstable index knee joint (such as a torn anterior cruciate ligament) within 12 months of Screening

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

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

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

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

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

• Any other IA drug/biologic in the index knee within 6 months of Screening or 5 half-lives (whichever is longer) (e.g., platelet rich plasma (PRP) injection, stem cells, prolotherapy and amniotic fluid injection)

• Prior administration of FX006

• eGFR results <40 mL/minute

• Any contraindication to MRI Scanning (e.g., presence of certain ferromagnetic foreign bodies or electronic devices including most cardiac pacemakers, claustrophobia)

• Known hypersensitivity to any form of radiographic contrast

• 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 Research	La Mesa	California	United States	91942
3	Dream Team Clinical Research (formerly located in Anaheim)	Pomona	California	United States	91767
4	Dream Team Clinical Research	Pomona	California	United States	91767
5	Tampa Bay Medical Research, Inc.	Clearwater	Florida	United States	33761
6	Rush University Medical Center	Chicago	Illinois	United States	60612
7	Duke University Medical Center	Durham	North Carolina	United States	27710
8	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
9	PMG Research, Inc. d/b/a PMG Research of Knoxville	Knoxville	Tennessee	United States	37938
10	University of Leeds	Leeds		United Kingdom	LS7 4SA

Sponsors and Collaborators

• Flexion Therapeutics, Inc.

Investigators

• Study Director: Scott Kelley, MD, Flexion Therapeutics

Study Documents (Full-Text)

• Study Protocol - Jul 12, 2019
• Statistical Analysis Plan - Nov 5, 2019
• Informed Consent Form - May 9, 2019

More Information

Publications

None provided.

• Responsible Party: Flexion Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03529942
• Other Study ID Numbers: FX006-2017-014
• First Posted: May 18, 2018
• 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; Knee; Pain; Intra-articular; Injection; Corticosteroid
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Inflammation; FX006

Study Results

Participant Flow

Arm/Group Title	FX006 32mg
Arm/Group Description	All patients who received any amount of FX006 32mg
Period Title: Overall Study
STARTED	129
Reached Week 6 With Paired MRI	108
COMPLETED	106
NOT COMPLETED	23

Baseline Characteristics

Arm/Group Title	Total Population
Arm/Group Description	All patients who received any amount of FX006 32mg
Overall Participants	129
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	85 65.9%
>=65 years	44 34.1%
Sex: Female, Male (Count of Participants)
Female	81 62.8%
Male	48 37.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.8%
Asian	2 1.6%
Native Hawaiian or Other Pacific Islander	2 1.6%
Black or African American	16 12.4%
White	108 83.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	129 100%

Outcome Measures

1. Primary Outcome

Title	Mean Standardized Change in Synovial Volume (SV) at 6 Weeks
Description	Synovial volume (mm^3) as measured by MRI and read by a central imaging vendor. Standardization was performed by dividing the model-derived least squares means and corresponding confidence intervals by the adjusted standard deviation (SD). Therefore, the mean standardized change represents the change in synovial volume expressed in standard deviation units.
Time Frame	Baseline to Week 6

Outcome Measure Data

Analysis Population Description

Participants with pre-treatment synovial volume measurement as determined by quantitative image analysis, as well as a quality Week 6 MRI who received a single intra-articular (IA) injection of FX006 32 mg

Arm/Group Title	Total Population	Patients With Baseline Synovitis
Arm/Group Description	All patients who received a single intra-articular (IA) injection of FX006 32mg and had a pre-treatment synovial volume measurement	The subset of the Total Population who had a pre-treatment synovial volume measurement of greater than 3000 mm^3 of gadolinium enhancement as determined by quantitative image analysis
Measure Participants	108	84
Least Squares Mean (95% Confidence Interval) [Standardized Units]	-0.67	-0.9

2. Secondary Outcome

Title	Mean Absolute Change in Synovial Volume at 6 Weeks
Description	Mean absolute change from baseline at 6 weeks in synovial volume (mm^3) as measured by MRI and read by a central imaging vendor. The least squares mean changes are estimated using a mixed effects model for repeated measures with fixed effects for study time point, study site, baseline score and baseline femur bone volume (mm^3) and a random effect for patient.
Time Frame	Baseline to Week 6

Outcome Measure Data

Analysis Population Description

Participants with pre treatment synovial volume measurement as determined by quantitative image analysis, as well as a quality Week 6 MRI who received a single intra-articular (IA) injection of FX006 32 mg

Arm/Group Title	Total Population	Patients With Baseline Synovitis
Arm/Group Description	All patients who received a single intra-articular (IA) injection of FX006 32mg and had a pre-treatment synovial volume measurement	The subset of the Total Population who had a pre-treatment synovial volume measurement of greater than 3000 mm^3 of gadolinium enhancement as determined by quantitative image analysis
Measure Participants	108	84
Least Squares Mean (Standard Error) [mm^3]	-5469.68 (581.9123)	-7549.55 (683.6488)

3. Secondary Outcome

Title	Mean Standardized Change in Synovial Volume (SV) at 24 Weeks
Description	Synovial volume (mm^3) as measured by MRI and read by a central imaging vendor. Standardization was performed by dividing the model-derived least squares means and corresponding confidence intervals by the adjusted standard deviation (SD). Therefore, the mean standardized change represents the change in synovial volume expressed in standard deviation units.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants with pre treatment synovial volume measurement as determined by quantitative image analysis, as well as a quality Week 24 MRI who received a single intra-articular (IA) injection of FX006 32 mg

Arm/Group Title	Total Population	Patients With Baseline Synovitis
Arm/Group Description	All patients who received a single intra-articular (IA) injection of FX006 32 mg and had a pre-treatment synovial volume measurement	The subset of the Total Population who had a pre-treatment synovial volume measurement of greater than 3000 mm^3 of gadolinium enhancement as determined by quantitative image analysis
Measure Participants	88	68
Least Squares Mean (95% Confidence Interval) [Standardized Units]	0.20	0.20

4. Secondary Outcome

Title	Mean Absolute Change in Synovial Volume at 24 Weeks
Description	Mean absolute change (mm^3) from baseline at 24 weeks in synovial volume (mm^3) as measured by MRI and read by a central imaging vendor. The least squares mean changes are estimated using a mixed effects model for repeated measures with fixed effects for study time point, study site, baseline score and baseline femur bone volume (mm^3) and a random effect for patient.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Participants with pre-treatment synovial volume measurement as determined by quantitative image analysis, as well as a quality Week 24 MRI who received a single intra-articular (IA) injection of FX006 32 mg.

Arm/Group Title	Total Population	Patients With Baseline Synovitis
Arm/Group Description	All patients who received a single intra-articular (IA) injection of FX006 32 mg and had a pre-treatment synovial volume measurement	The subset of the Total Population who had a pre-treatment synovial volume measurement of greater than 3000 mm^3 of gadolinium enhancement as determined by quantitative image analysis
Measure Participants	88	68
Least Squares Mean (Standard Error) [mm^3]	3239.94 (1184.5800)	3476.52 (1408.7997)

Adverse Events

Time Frame	Through study completion; up to 28 weeks
Arm/Group Title	Total Population		Patients With Baseline Synovitis
Arm/Group Description	All patients who received an attempted single intra-articular (IA) injection of FX006 32 mg		The subset of the Total Population who had a pre-treatment synovial volume measurement of greater than 3000 mm^3 of gadolinium enhancement as determined by quantitative image analysis
All Cause Mortality
	Total Population		Patients With Baseline Synovitis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/129 (0%)		0/102 (0%)
Serious Adverse Events
	Total Population		Patients With Baseline Synovitis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/129 (0.8%)		1/102 (1%)
Renal and urinary disorders
Nephrolithiasis	1/129 (0.8%)	1	1/102 (1%)	1
Other (Not Including Serious) Adverse Events
	Total Population		Patients With Baseline Synovitis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/129 (24%)		28/102 (27.5%)
Blood and lymphatic system disorders
Anaemia	1/129 (0.8%)	1	0/102 (0%)	0
Lymph Node Pain	1/129 (0.8%)	1	0/102 (0%)	0
Cardiac disorders
Atrial Fibrillation	1/129 (0.8%)	1	1/102 (1%)	1
Endocrine disorders
Thyroid Cyst	1/129 (0.8%)	1	1/102 (1%)	1
Gastrointestinal disorders
Diarrhoea	1/129 (0.8%)	1	1/102 (1%)	1
Gastritis	1/129 (0.8%)	1	0/102 (0%)	0
General disorders
Oedema Peripheral	2/129 (1.6%)	2	2/102 (2%)	2
Pyrexia	1/129 (0.8%)	1	1/102 (1%)	1
Infections and infestations
Acute Sinusitis	1/129 (0.8%)	1	1/102 (1%)	1
Otitis Media	1/129 (0.8%)	1	1/102 (1%)	1
Upper Respiratory Tract Infection	2/129 (1.6%)	2	2/102 (2%)	2
Injury, poisoning and procedural complications
Contusion	1/129 (0.8%)	1	1/102 (1%)	1
Fall	1/129 (0.8%)	1	1/102 (1%)	1
Joint Injury	1/129 (0.8%)	1	1/102 (1%)	1
Limb Injury	1/129 (0.8%)	1	1/102 (1%)	1
Meniscus Injury	1/129 (0.8%)	1	1/102 (1%)	1
Procedural Anxiety	1/129 (0.8%)	1	1/102 (1%)	1
Synovial Rupture	1/129 (0.8%)	1	1/102 (1%)	1
Investigations
Alanine Aminotransferase Increased	1/129 (0.8%)	1	0/102 (0%)	0
Aspartate Aminotransferase Increased	1/129 (0.8%)	1	0/102 (0%)	0
Cardiac Murmur	1/129 (0.8%)	1	0/102 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	7/129 (5.4%)	8	7/102 (6.9%)	8
Back Pain	2/129 (1.6%)	2	2/102 (2%)	2
Joint Effusion	1/129 (0.8%)	1	1/102 (1%)	1
Joint Swelling	1/129 (0.8%)	1	1/102 (1%)	1
Muscle Spasms	1/129 (0.8%)	1	1/102 (1%)	1
Osteoarthritis	1/129 (0.8%)	1	1/102 (1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma	1/129 (0.8%)	1	1/102 (1%)	1
Nervous system disorders
Dizziness	2/129 (1.6%)	2	2/102 (2%)	2
Headache	1/129 (0.8%)	1	1/102 (1%)	1
Presyncope	1/129 (0.8%)	1	1/102 (1%)	1
Renal and urinary disorders
Nephrolithiasis	1/129 (0.8%)	1	1/102 (1%)	1
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain	1/129 (0.8%)	1	1/102 (1%)	1
Skin and subcutaneous tissue disorders
Psoriasis	1/129 (0.8%)	1	1/102 (1%)	1

Limitations/Caveats

One patient experienced procedural anxiety during the placement of the syringe on the inserted needle and did not receive the full dose of FX006. This patient is still counted in the safety population.

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.