Trial Outcomes & Findings for Study to Assess the Safety of Repeat Administration of FX006 Administered to Patients With Osteoarthritis of the Knee (NCT NCT03046446)
NCT ID: NCT03046446
Last Updated: 2024-01-24
Results Overview
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).
COMPLETED
PHASE3
208 participants
Up to 52 Weeks
2024-01-24
Participant Flow
Participant milestones
| Measure |
FX006 32 mg
Single intra-articular injection
FX006 32 mg: Single intra-articular injection
|
|---|---|
|
Overall Study
STARTED
|
208
|
|
Overall Study
Second Injection
|
179
|
|
Overall Study
Completed at Week 12
|
10
|
|
Overall Study
Completed at Week 24
|
6
|
|
Overall Study
Completed at Week 52
|
133
|
|
Overall Study
COMPLETED
|
149
|
|
Overall Study
NOT COMPLETED
|
59
|
Reasons for withdrawal
| Measure |
FX006 32 mg
Single intra-articular injection
FX006 32 mg: Single intra-articular injection
|
|---|---|
|
Overall Study
Lack of Efficacy
|
7
|
|
Overall Study
Adverse Event
|
6
|
|
Overall Study
Lost to Follow-up
|
3
|
|
Overall Study
Withdrawal by Subject
|
14
|
|
Overall Study
Withdrawn by Investigator/Sponsor
|
3
|
|
Overall Study
Disease Progression (see caveats)
|
25
|
|
Overall Study
Non OA related knee surgery
|
1
|
Baseline Characteristics
Study to Assess the Safety of Repeat Administration of FX006 Administered to Patients With Osteoarthritis of the Knee
Baseline characteristics by cohort
| Measure |
FX006 32 mg
n=208 Participants
Single intra-articular injection
FX006 32 mg: Single intra-articular injection
|
|---|---|
|
Age, Continuous
|
60.8 years
STANDARD_DEVIATION 8.81 • n=5 Participants
|
|
Sex: Female, Male
Female
|
92 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
116 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
170 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
208 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 52 WeeksPopulation: Received 2 doses of 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).
Outcome measures
| Measure |
FX006 32 mg
n=179 Participants
Single intra-articular injection
FX006 32 mg: Single intra-articular injection
|
|---|---|
|
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
|
336 TEAEs
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 Weeks Post Each FX006 AdministrationPopulation: Participants who received a repeat administration of FX006 at weeks 12, 16, 20 or 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. 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.
Outcome measures
| Measure |
FX006 32 mg
n=178 Participants
Single intra-articular injection
FX006 32 mg: Single intra-articular injection
|
|---|---|
|
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale
Baseline - First Administration
|
2.15 score on a scale
Standard Deviation 0.580
|
|
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale
4 Weeks Post First Administration
|
0.66 score on a scale
Standard Deviation 0.581
|
|
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale
8 Weeks Post First Administration
|
0.83 score on a scale
Standard Deviation 0.663
|
|
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale
12 Weeks Post First Administration
|
1.29 score on a scale
Standard Deviation 0.765
|
|
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale
Baseline - Second Administration
|
2.00 score on a scale
Standard Deviation 0.639
|
|
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale
4 Weeks Post Second Administration
|
0.83 score on a scale
Standard Deviation 0.667
|
|
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale
8 Weeks Post Second Administration
|
0.93 score on a scale
Standard Deviation 0.691
|
|
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale
12 Weeks Post Second Administration
|
1.28 score on a scale
Standard Deviation 0.862
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 Weeks Post Each FX006 AdministrationPopulation: Participants who received a repeat administration of FX006 at weeks 12, 16, 20 or 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. 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.
Outcome measures
| Measure |
FX006 32 mg
n=178 Participants
Single intra-articular injection
FX006 32 mg: Single intra-articular injection
|
|---|---|
|
WOMAC B Stiffness Subscale
Baseline - First Administration
|
2.48 score on a scale
Standard Deviation 0.715
|
|
WOMAC B Stiffness Subscale
4 Weeks Post First Administration
|
0.74 score on a scale
Standard Deviation 0.662
|
|
WOMAC B Stiffness Subscale
8 Weeks Post First Administration
|
0.90 score on a scale
Standard Deviation 0.749
|
|
WOMAC B Stiffness Subscale
12 Weeks Post First Administration
|
1.41 score on a scale
Standard Deviation 0.936
|
|
WOMAC B Stiffness Subscale
Baseline - Second Administration
|
2.16 score on a scale
Standard Deviation 0.824
|
|
WOMAC B Stiffness Subscale
4 Weeks Post Second Administration
|
0.88 score on a scale
Standard Deviation 0.764
|
|
WOMAC B Stiffness Subscale
8 Weeks Post Second Administration
|
0.99 score on a scale
Standard Deviation 0.837
|
|
WOMAC B Stiffness Subscale
12 Weeks Post Second Administration
|
1.40 score on a scale
Standard Deviation 1.007
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 Weeks Post Each FX006 AdministrationPopulation: Participants who received a repeat administration of FX006 at weeks 12, 16, 20 or 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. 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.
Outcome measures
| Measure |
FX006 32 mg
n=178 Participants
Single intra-articular injection
FX006 32 mg: Single intra-articular injection
|
|---|---|
|
WOMAC C Function Subscale
Baseline - First Administration
|
2.18 score on a scale
Standard Deviation 0.613
|
|
WOMAC C Function Subscale
4 Weeks Post First Administration
|
0.66 score on a scale
Standard Deviation 0.593
|
|
WOMAC C Function Subscale
8 Weeks Post First Administration
|
0.87 score on a scale
Standard Deviation 0.711
|
|
WOMAC C Function Subscale
12 Weeks Post First Administration
|
1.28 score on a scale
Standard Deviation 0.801
|
|
WOMAC C Function Subscale
Baseline - Second Administration
|
1.96 score on a scale
Standard Deviation 0.692
|
|
WOMAC C Function Subscale
4 Weeks Post Second Administration
|
0.85 score on a scale
Standard Deviation 0.685
|
|
WOMAC C Function Subscale
8 Weeks Post Second Administration
|
0.96 score on a scale
Standard Deviation 0.699
|
|
WOMAC C Function Subscale
12 Weeks Post Second Administration
|
1.31 score on a scale
Standard Deviation 0.845
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 12 Weeks Post Each FX006 AdministrationPopulation: Participants who received a repeat administration of FX006
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.
Outcome measures
| Measure |
FX006 32 mg
n=178 Participants
Single intra-articular injection
FX006 32 mg: Single intra-articular injection
|
|---|---|
|
Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale
Baseline - First Administration
|
28.92 score on a scale
Standard Deviation 15.872
|
|
Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale
4 Weeks Post First Administration
|
58.06 score on a scale
Standard Deviation 22.049
|
|
Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale
8 Weeks Post First Administration
|
55.34 score on a scale
Standard Deviation 21.791
|
|
Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale
12 Weeks Post First Administration
|
46.08 score on a scale
Standard Deviation 20.860
|
|
Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale
Baseline - Second Administration
|
33.47 score on a scale
Standard Deviation 17.270
|
|
Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale
4 Weeks Post Second Administration
|
54.85 score on a scale
Standard Deviation 20.927
|
|
Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale
8 Weeks Post Second Administration
|
50.92 score on a scale
Standard Deviation 20.781
|
|
Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale
12 Weeks Post Second Administration
|
46.52 score on a scale
Standard Deviation 23.274
|
Adverse Events
FX006 32 mg
Serious adverse events
| Measure |
FX006 32 mg
n=208 participants at risk
Single intra-articular injection
FX006 32 mg: Single intra-articular injection
|
|---|---|
|
Gastrointestinal disorders
Pancreatitis
|
0.48%
1/208 • 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.
|
|
Nervous system disorders
Syncope
|
0.48%
1/208 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.48%
1/208 • 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.
|
|
Gastrointestinal disorders
Diverticulum
|
0.48%
1/208 • 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.
|
Other adverse events
| Measure |
FX006 32 mg
n=208 participants at risk
Single intra-articular injection
FX006 32 mg: Single intra-articular injection
|
|---|---|
|
Infections and infestations
Influenza
|
2.4%
5/208 • 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.
|
|
Infections and infestations
Nasopharyngitis
|
2.4%
5/208 • 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.
|
|
Infections and infestations
Upper respiratory tract infection
|
7.7%
16/208 • 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.
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
2.4%
5/208 • 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.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
28.8%
60/208 • 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.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.8%
8/208 • 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.
|
|
Musculoskeletal and connective tissue disorders
Joint crepitation
|
3.4%
7/208 • 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.
|
|
Musculoskeletal and connective tissue disorders
Joint effusion
|
2.9%
6/208 • 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.
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
3.8%
8/208 • 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.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
4.3%
9/208 • 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.
|
Additional Information
Scott Kelley, Chief Medical Officer
Flexion Therapeutics
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place