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This is an Open-label Study to Assess the Safety of Repeat Dose of FX006 Administered to Patients with Osteoarthritis (OA) of the Knee
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FX006 32 mg | Experimental | Single intra-articular injection |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FX006 32 mg | Drug | Single intra-articular injection |
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| Measure | Description | Time Frame |
|---|---|---|
| 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). | Up to 52 Weeks |
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| Measure | Description | Time Frame |
|---|---|---|
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale | 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Scott Kelley, MD | Flexion Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tucson Orthopedic | Tucson | Arizona | 85712 | United States | ||
| Dream Team Clinical Research |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30741382 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | FX006 32 mg | Single intra-articular injection FX006 32 mg: Single intra-articular injection |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 16, 2017 | Jul 17, 2019 |
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| 12 Weeks Post Each FX006 Administration |
| WOMAC B Stiffness Subscale | 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. | 12 Weeks Post Each FX006 Administration |
| WOMAC C Function Subscale | 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. | 12 Weeks Post Each FX006 Administration |
| Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale | 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. | Up to 12 Weeks Post Each FX006 Administration |
| Anaheim |
| California |
| 92801 |
| United States |
| Hope Clinical Research | Canoga Park | California | 91303 | United States |
| Cedars-Sinai Medical Center | Los Angeles | California | 90048 | United States |
| Artemis Institute for Clinical Research | San Diego | California | 92103 | United States |
| Harbor-UCLA Medical Center | Torrance | California | 90509 | United States |
| Tampa Bay Medical Research | Clearwater | Florida | 37761 | United States |
| The Andrews Institute | Gulf Breeze | Florida | 32561 | United States |
| Ochsner Sports Medicine Institute | New Orleans | Louisiana | 70121 | United States |
| Brigham and Women's Hospital | Chestnut Hill | Massachusetts | 02467 | United States |
| New England Baptist Hospital | Dedham | Massachusetts | 02026 | United States |
| Rochester Clinical Research | Rochester | New York | 14609 | United States |
| Duke University | Durham | North Carolina | 27701 | United States |
| Altoona Center for Clinical Research | Duncansville | Pennsylvania | 16635 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| Coastal Carolina Research Center | Mt. Pleasant | South Carolina | 29464 | United States |
| PMG Research of Knoxville | Knoxville | Tennessee | 37938 | United States |
| Second Injection | 1 patient received 2nd injection after week 24 and is not included in the efficacy data analysis. |
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| Completed at Week 12 |
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| Completed at Week 24 |
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| Completed at Week 52 |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | FX006 32 mg | Single intra-articular injection FX006 32 mg: Single intra-articular injection |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Received 2 doses of FX006 | Posted | Number | TEAEs | Up to 52 Weeks |
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| ||||||||||||||||||||||||||
| Other Pre-specified | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale | 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. | Participants who received a repeat administration of FX006 at weeks 12, 16, 20 or 24. | Posted | Mean | Standard Deviation | score on a scale | 12 Weeks Post Each FX006 Administration |
|
| ||||||||||||||||||||||||||
| Other Pre-specified | WOMAC B Stiffness Subscale | 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. | Participants who received a repeat administration of FX006 at weeks 12, 16, 20 or 24. | Posted | Mean | Standard Deviation | score on a scale | 12 Weeks Post Each FX006 Administration |
|
| ||||||||||||||||||||||||||
| Other Pre-specified | WOMAC C Function Subscale | 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. | Participants who received a repeat administration of FX006 at weeks 12, 16, 20 or 24. | Posted | Mean | Standard Deviation | score on a scale | 12 Weeks Post Each FX006 Administration |
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| ||||||||||||||||||||||||||
| Other Pre-specified | Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale | 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. | Participants who received a repeat administration of FX006 | Posted | Mean | Standard Deviation | score on a scale | Up to 12 Weeks Post Each FX006 Administration |
|
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For patients who received a single injection, adverse events were collected following intra-articular (IA) administration through the final study visit at week 24. For patients who received a repeat injection, adverse events were collected following first IA administration through the final study visit at week 52.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | FX006 32 mg | Single intra-articular injection FX006 32 mg: Single intra-articular injection | 0 | 208 | 4 | 208 | 93 | 208 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pancreatitis | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Diverticulum | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Influenza | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
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| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| Joint crepitation | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| Joint effusion | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
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Disease progression defined as response to first and second injections but loss of effect sometime after the response to the second injection. All discontinuations because of disease progression occurred ≥ 12 weeks after the second injection.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Scott Kelley, Chief Medical Officer | Flexion Therapeutics | 781-305-7142 | skelley@flexiontherapeutics.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 1, 2018 | Jul 17, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D020370 | Osteoarthritis, Knee |
| D010003 | Osteoarthritis |
| D010146 | Pain |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000631825 | FX006 |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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