Study to Assess the Safety of Repeat Administration of FX006 Administered to Patients With Osteoarthritis of the Knee
Primary Purpose
Osteoarthritis of the Knee
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
FX006 32 mg
Sponsored by
About this trial
This is an interventional treatment trial for Osteoarthritis of the Knee focused on measuring Osteoarthritis, Knee, Pain, Steroid, Intra-articular, Injection
Eligibility Criteria
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
- Male or female ≥ 40 years of age
- Symptoms associated with OA of the index knee for ≥ 6 months prior to Screening
- Currently meets American College of Rheumatology (ACR) Criteria (clinical and radiological) for OA
- Kellgren-Lawrence (KL) Grade 2, 3 or 4 in the index knee based on X-ray performed during Screening
- Qualifying score for WOMAC A at Screening and Day 1/Baseline
- 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
- Willingness to abstain from use of protocol-restricted medications during the study
Exclusion Criteria:
- Reactive arthritis, 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 index knee joint (such as a torn anterior cruciate ligament) within 12 months of Screening
- IA corticosteroid (investigational or marketed) in index knee within 3 months of Screening
- IA hyaluronic acid (investigational or marketed) in the index knee within 6 months of Screening
- IV or intramuscular (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 use 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
- Women of child-bearing potential not using effective contraception or who are pregnant or nursing
Sites / Locations
- Tucson Orthopedic
- Dream Team Clinical Research
- Hope Clinical Research
- Cedars-Sinai Medical Center
- Artemis Institute for Clinical Research
- Harbor-UCLA Medical Center
- Tampa Bay Medical Research
- The Andrews Institute
- Ochsner Sports Medicine Institute
- Brigham and Women's Hospital
- New England Baptist Hospital
- Rochester Clinical Research
- Duke University
- Altoona Center for Clinical Research
- Medical University of South Carolina
- Coastal Carolina Research Center
- PMG Research of Knoxville
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
FX006 32 mg
Arm Description
Single intra-articular injection
Outcomes
Primary Outcome Measures
Total Number of Treatment Emergent Adverse Events (TEAEs) in Patients With Symptomatic Osteoarthritis (OA) of the Knee Who Received Two Doses of 32 mg FX006
Analyses of adverse events (AE) were performed for events considered treatment-emergent (TE) in patients who received two doses of 32 mg FX006. TE was defined as any AE with onset after administration of the 1st dose of study drug or any event present at baseline but worsened in intensity through the study. Severity was graded by the PI using the Common Terminology Criteria for AEs Version 4.0. Grading went from Grade 1 (Mild) to Grade 5 (Death Related to AE).
Secondary Outcome Measures
Full Information
NCT ID
NCT03046446
First Posted
February 6, 2017
Last Updated
October 11, 2019
Sponsor
Flexion Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03046446
Brief Title
Study to Assess the Safety of Repeat Administration of FX006 Administered to Patients With Osteoarthritis of the Knee
Official Title
An Open-label Study to Assess the Safety of Repeat Administration of FX006 to Patients With Osteoarthritis of the Knee
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
February 20, 2017 (Actual)
Primary Completion Date
July 19, 2018 (Actual)
Study Completion Date
July 19, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Flexion Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is an Open-label Study to Assess the Safety of Repeat Dose of FX006 Administered to Patients with Osteoarthritis (OA) of the Knee
Detailed Description
This study is an open-label, repeat administration design of 32 mg FX006. The study will be conducted in male and female patients ≥ 40 years of age with symptomatic OA of the knee.
Eligible patients will be offered participation to receive an initial intra-articular (IA) injection of FX006 administered to the index knee at Day 1.
Patients who receive an initial injection of FX006 will return at Weeks 4 and 8 before being evaluated at 12, 16, 20 and 24 weeks for repeat administration. At the first evaluation where the patient has been determined to meet repeat administration eligibility criteria, the patient will be eligible to receive a second IA injection of FX006.
Patients who are eligible to receive a second injection will be evaluated for a total of 52 weeks post initial injection at: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52, regardless of the time at which they receive their second injection. In addition, X-rays will be completed at Screening and Week 52 or End of Study (EOS) for assessment of safety.
Patients that do not benefit from the initial treatment as determined by evaluation at Week 12 will complete the study at the Week 12 follow-up visit.
Patients who are not eligible for a second injection of FX006 after evaluation at Weeks 12, 16, 20, and 24 will complete the study at the Week 24 follow-up visit.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis of the Knee
Keywords
Osteoarthritis, Knee, Pain, Steroid, Intra-articular, Injection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
208 (Actual)
8. Arms, Groups, and Interventions
Arm Title
FX006 32 mg
Arm Type
Experimental
Arm Description
Single intra-articular injection
Intervention Type
Drug
Intervention Name(s)
FX006 32 mg
Intervention Description
Single intra-articular injection
Primary Outcome Measure Information:
Title
Total Number of Treatment Emergent Adverse Events (TEAEs) in Patients With Symptomatic Osteoarthritis (OA) of the Knee Who Received Two Doses of 32 mg FX006
Description
Analyses of adverse events (AE) were performed for events considered treatment-emergent (TE) in patients who received two doses of 32 mg FX006. TE was defined as any AE with onset after administration of the 1st dose of study drug or any event present at baseline but worsened in intensity through the study. Severity was graded by the PI using the Common Terminology Criteria for AEs Version 4.0. Grading went from Grade 1 (Mild) to Grade 5 (Death Related to AE).
Time Frame
Up to 52 Weeks
Other Pre-specified Outcome Measures:
Title
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain 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. WOMAC A is the independent sub-scale for pain that is comprised of 5 questions.
WOMAC A was administered at each visit from screening through Week 52/EOS.
Time Frame
12 Weeks Post Each FX006 Administration
Title
WOMAC B Stiffness 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. WOMAC B is the independent sub-scale for stiffness that is comprised of 2 questions.
WOMAC B was administered at each visit from screening through Week 52/EOS.
Time Frame
12 Weeks Post Each FX006 Administration
Title
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. WOMAC C is the independent sub-scale for function that is comprised of 17 questions.
WOMAC C was administered at each visit from screening through Week 52/EOS.
Time Frame
12 Weeks Post Each FX006 Administration
Title
Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale
Description
KOOS is a participant (patient)-reported outcome measurement instrument, developed to assess the patient's opinion about their knee and associated problems. The KOOS evaluates both short-term and long-term consequences of knee injury and also consequences of primary osteoarthritis (OA). It holds 42 items in five separately scored sub-scales: KOOS Pain, KOOS Symptoms, Function in daily living, Function in Sport and Recreation, and knee-related Quality of Life (KOOS QOL). Only KOOS QOL sub-scale (Q1-Q4) was used in this study.
A Likert scale is used and all items have five possible answer options scored from 0 (No Problem) to 4 (Extreme Problems). Each of the five scores is calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems. Higher scores indicate a better quality of life.
KOOS was administered at study visits from BL/Day 1 through week 52.
Time Frame
Up to 12 Weeks Post Each FX006 Administration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Male or female ≥ 40 years of age
Symptoms associated with OA of the index knee for ≥ 6 months prior to Screening
Currently meets American College of Rheumatology (ACR) Criteria (clinical and radiological) for OA
Kellgren-Lawrence (KL) Grade 2, 3 or 4 in the index knee based on X-ray performed during Screening
Qualifying score for WOMAC A at Screening and Day 1/Baseline
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
Willingness to abstain from use of protocol-restricted medications during the study
Exclusion Criteria:
Reactive arthritis, 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 index knee joint (such as a torn anterior cruciate ligament) within 12 months of Screening
IA corticosteroid (investigational or marketed) in index knee within 3 months of Screening
IA hyaluronic acid (investigational or marketed) in the index knee within 6 months of Screening
IV or intramuscular (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 use 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
Women of child-bearing potential not using effective contraception or who are pregnant or nursing
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott Kelley, MD
Organizational Affiliation
Flexion Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Tucson Orthopedic
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85712
Country
United States
Facility Name
Dream Team Clinical Research
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
Hope Clinical Research
City
Canoga Park
State/Province
California
ZIP/Postal Code
91303
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Artemis Institute for Clinical Research
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Harbor-UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90509
Country
United States
Facility Name
Tampa Bay Medical Research
City
Clearwater
State/Province
Florida
ZIP/Postal Code
37761
Country
United States
Facility Name
The Andrews Institute
City
Gulf Breeze
State/Province
Florida
ZIP/Postal Code
32561
Country
United States
Facility Name
Ochsner Sports Medicine Institute
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Brigham and Women's Hospital
City
Chestnut Hill
State/Province
Massachusetts
ZIP/Postal Code
02467
Country
United States
Facility Name
New England Baptist Hospital
City
Dedham
State/Province
Massachusetts
ZIP/Postal Code
02026
Country
United States
Facility Name
Rochester Clinical Research
City
Rochester
State/Province
New York
ZIP/Postal Code
14609
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27701
Country
United States
Facility Name
Altoona Center for Clinical Research
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Coastal Carolina Research Center
City
Mount Pleasant
State/Province
South Carolina
ZIP/Postal Code
29464
Country
United States
Facility Name
PMG Research of Knoxville
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37938
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30741382
Citation
Spitzer AI, Richmond JC, Kraus VB, Gomoll A, Jones DG, Huffman KM, Peterfy C, Cinar A, Lufkin J, Kelley SD. Safety and Efficacy of Repeat Administration of Triamcinolone Acetonide Extended-release in Osteoarthritis of the Knee: A Phase 3b, Open-label Study. Rheumatol Ther. 2019 Mar;6(1):109-124. doi: 10.1007/s40744-019-0140-z. Epub 2019 Feb 11.
Results Reference
derived
Learn more about this trial
Study to Assess the Safety of Repeat Administration of FX006 Administered to Patients With Osteoarthritis of the Knee
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