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

• ClinicalTrials.gov Identifier: NCT03529942
• Recruitment Status: Completed
• First Posted: May 18, 2018
• Results First Posted: December 8, 2020
• Last Update Posted: December 8, 2020
• Sponsor: Flexion Therapeutics, Inc.
• Information provided by (Responsible Party): Flexion Therapeutics, Inc.

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 (Clinical Trial)
• 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: April 24, 2018
• Actual Primary Completion Date: November 8, 2019
• Actual Study Completion Date: March 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 Name: Zilretta

Outcome Measures

Primary Outcome Measures :

1. Mean Standardized Change in Synovial Volume (SV) at 6 Weeks [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

United States, California

TriWest Research Associates, LLC

El Cajon, California, United States, 92020

Biosolutions Research

La Mesa, California, United States, 91942

Dream Team Clinical Research (formerly located in Anaheim)

Pomona, California, United States, 91767

Dream Team Clinical Research

Pomona, California, United States, 91767

United States, Florida

Tampa Bay Medical Research, Inc.

Clearwater, Florida, United States, 33761

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, Pennsylvania

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States, 16635

United States, Tennessee

PMG Research, Inc. d/b/a PMG Research of Knoxville

Knoxville, Tennessee, United States, 37938

United Kingdom

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)

Documents provided by Flexion Therapeutics, Inc.:

Study Protocol  [PDF] July 12, 2019

Informed Consent Form  [PDF] May 9, 2019

Statistical Analysis Plan  [PDF] November 5, 2019

More Information

• Responsible Party: Flexion Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03529942
• Other Study ID Numbers: FX006-2017-014
• First Posted: May 18, 2018
• Results First Posted: December 8, 2020
• Last Update Posted: December 8, 2020
• Last Verified: December 2020

• 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; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Pathologic Processes