Trial Outcomes & Findings for Study to Determine the Safety and the Efficacy of Fasinumab Compared to Placebo and Nonsteroidal Anti-inflammatory Drugs (NSAIDs) for Treatment of Adults With Pain From Osteoarthritis of the Knee or Hip (NCT NCT03304379)
NCT ID: NCT03304379
Last Updated: 2023-02-24
Results Overview
WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in past 48 hours. It was calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (higher pain), where higher scores indicated higher pain.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1650 participants
Primary outcome timeframe
Baseline up to Week 24
Results posted on
2023-02-24
Participant Flow
A total of 4531 participants were screened in this study. Out of which, 1650 participants were randomized to 1 of the following arms: Fasinumab (1 milligram \[mg\]), non-steroidal anti-inflammatory drug (NSAIDs), matched placebo, Fasinumab 3 and 6 mg. Screen failure was mostly due to inclusion criteria not met/exclusion criteria met. Eligible participants were randomized to receive placebo matched to Fasinumab/NSAIDs, NSAIDs (Diclofenac and Celecoxib) and Fasinumab 1 mg.
In May 2018, the sponsor implemented an urgent safety measure to stop dosing for participants randomized to Fasinumab (6 mg and 3 mg), to prevent further randomization to these regimens across the Fasinumab program based on review of unblinded data in an ongoing study R475-PN-1523 (NCT02683239). Participants from Fasinumab 3 mg and 6 mg group were moved directly into the 20-week follow-up period.
Participant milestones
| Measure |
Placebo
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
NSAIDs
Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks.
|
Fasinumab 1 mg
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 3 mg
Participants received SC injection of Fasinumab at a dose of 3 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 6 mg
Participants received SC injection of Fasinumab at a dose of 6 mg Q8W up to 24 weeks, alternating with Q8W placebo injections. Participants received placebo injections at the Q4W study visits where study drug was not administered and NSAID-matching placebo oral, BID
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
308
|
612
|
612
|
59
|
59
|
|
Overall Study
Full Analysis Set (FAS)
|
308
|
612
|
612
|
0
|
0
|
|
Overall Study
Safety Analysis Set (SAF)
|
309
|
609
|
609
|
0
|
0
|
|
Overall Study
Urgent Safety Measure Set (USMS)
|
0
|
0
|
0
|
59
|
59
|
|
Overall Study
Completed Treatment
|
218
|
436
|
454
|
0
|
0
|
|
Overall Study
COMPLETED
|
238
|
471
|
463
|
42
|
42
|
|
Overall Study
NOT COMPLETED
|
70
|
141
|
149
|
17
|
17
|
Reasons for withdrawal
| Measure |
Placebo
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
NSAIDs
Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks.
|
Fasinumab 1 mg
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 3 mg
Participants received SC injection of Fasinumab at a dose of 3 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 6 mg
Participants received SC injection of Fasinumab at a dose of 6 mg Q8W up to 24 weeks, alternating with Q8W placebo injections. Participants received placebo injections at the Q4W study visits where study drug was not administered and NSAID-matching placebo oral, BID
|
|---|---|---|---|---|---|
|
Overall Study
Protocol Violation
|
8
|
10
|
5
|
0
|
2
|
|
Overall Study
Adverse Event
|
4
|
20
|
17
|
1
|
0
|
|
Overall Study
Lack of Efficacy
|
17
|
16
|
20
|
0
|
0
|
|
Overall Study
Physician Decision
|
6
|
10
|
6
|
9
|
10
|
|
Overall Study
Withdrawal by Subject
|
26
|
58
|
66
|
3
|
5
|
|
Overall Study
Lost to Follow-up
|
8
|
24
|
35
|
4
|
0
|
|
Overall Study
Death
|
1
|
2
|
0
|
0
|
0
|
|
Overall Study
Other
|
0
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Here 'n' = number of evaluable participants at the specified time point
Baseline characteristics by cohort
| Measure |
Placebo
n=308 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
NSAIDs
n=612 Participants
Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks.
|
Fasinumab 1 mg
n=612 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 3 mg
n=59 Participants
Participants received SC injection of Fasinumab at a dose of 3 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 6 mg
n=59 Participants
Participants received SC injection of Fasinumab at a dose of 6 mg Q8W up to 24 weeks, alternating with Q8W placebo injections. Participants received placebo injections at the Q4W study visits where study drug was not administered and NSAID-matching placebo oral, BID
|
Total
n=1650 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
62.0 Years
STANDARD_DEVIATION 9.30 • n=308 Participants
|
62.3 Years
STANDARD_DEVIATION 9.41 • n=612 Participants
|
62.1 Years
STANDARD_DEVIATION 9.13 • n=612 Participants
|
62.8 Years
STANDARD_DEVIATION 9.38 • n=59 Participants
|
61.5 Years
STANDARD_DEVIATION 9.55 • n=59 Participants
|
62.2 Years
STANDARD_DEVIATION 9.28 • n=1650 Participants
|
|
Sex: Female, Male
Female
|
222 Participants
n=308 Participants
|
418 Participants
n=612 Participants
|
436 Participants
n=612 Participants
|
36 Participants
n=59 Participants
|
34 Participants
n=59 Participants
|
1146 Participants
n=1650 Participants
|
|
Sex: Female, Male
Male
|
86 Participants
n=308 Participants
|
194 Participants
n=612 Participants
|
176 Participants
n=612 Participants
|
23 Participants
n=59 Participants
|
25 Participants
n=59 Participants
|
504 Participants
n=1650 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
20 Participants
n=308 Participants
|
44 Participants
n=612 Participants
|
31 Participants
n=612 Participants
|
5 Participants
n=59 Participants
|
10 Participants
n=59 Participants
|
110 Participants
n=1650 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
285 Participants
n=308 Participants
|
568 Participants
n=612 Participants
|
581 Participants
n=612 Participants
|
54 Participants
n=59 Participants
|
49 Participants
n=59 Participants
|
1537 Participants
n=1650 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=308 Participants
|
0 Participants
n=612 Participants
|
0 Participants
n=612 Participants
|
0 Participants
n=59 Participants
|
0 Participants
n=59 Participants
|
3 Participants
n=1650 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=308 Participants
|
0 Participants
n=612 Participants
|
2 Participants
n=612 Participants
|
0 Participants
n=59 Participants
|
0 Participants
n=59 Participants
|
2 Participants
n=1650 Participants
|
|
Race (NIH/OMB)
Asian
|
33 Participants
n=308 Participants
|
57 Participants
n=612 Participants
|
54 Participants
n=612 Participants
|
8 Participants
n=59 Participants
|
3 Participants
n=59 Participants
|
155 Participants
n=1650 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=308 Participants
|
0 Participants
n=612 Participants
|
1 Participants
n=612 Participants
|
0 Participants
n=59 Participants
|
0 Participants
n=59 Participants
|
2 Participants
n=1650 Participants
|
|
Race (NIH/OMB)
Black or African American
|
60 Participants
n=308 Participants
|
134 Participants
n=612 Participants
|
132 Participants
n=612 Participants
|
12 Participants
n=59 Participants
|
16 Participants
n=59 Participants
|
354 Participants
n=1650 Participants
|
|
Race (NIH/OMB)
White
|
202 Participants
n=308 Participants
|
396 Participants
n=612 Participants
|
405 Participants
n=612 Participants
|
39 Participants
n=59 Participants
|
40 Participants
n=59 Participants
|
1082 Participants
n=1650 Participants
|
|
Race (NIH/OMB)
More than one race
|
11 Participants
n=308 Participants
|
24 Participants
n=612 Participants
|
18 Participants
n=612 Participants
|
0 Participants
n=59 Participants
|
0 Participants
n=59 Participants
|
53 Participants
n=1650 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=308 Participants
|
1 Participants
n=612 Participants
|
0 Participants
n=612 Participants
|
0 Participants
n=59 Participants
|
0 Participants
n=59 Participants
|
2 Participants
n=1650 Participants
|
|
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score
|
6.42 Score on a scale
STANDARD_DEVIATION 1.394 • n=308 Participants • Here 'n' = number of evaluable participants at the specified time point
|
6.38 Score on a scale
STANDARD_DEVIATION 1.344 • n=611 Participants • Here 'n' = number of evaluable participants at the specified time point
|
6.46 Score on a scale
STANDARD_DEVIATION 1.321 • n=612 Participants • Here 'n' = number of evaluable participants at the specified time point
|
6.43 Score on a scale
STANDARD_DEVIATION 1.401 • n=58 Participants • Here 'n' = number of evaluable participants at the specified time point
|
6.54 Score on a scale
STANDARD_DEVIATION 1.279 • n=59 Participants • Here 'n' = number of evaluable participants at the specified time point
|
6.42 Score on a scale
STANDARD_DEVIATION 1.344 • n=1648 Participants • Here 'n' = number of evaluable participants at the specified time point
|
|
WOMAC Physical Function Subscale Scores
|
6.40 Score on a scale
STANDARD_DEVIATION 1.495 • n=304 Participants • Here 'n' = number of evaluable participants at the specified time point
|
6.32 Score on a scale
STANDARD_DEVIATION 1.418 • n=609 Participants • Here 'n' = number of evaluable participants at the specified time point
|
6.39 Score on a scale
STANDARD_DEVIATION 1.462 • n=610 Participants • Here 'n' = number of evaluable participants at the specified time point
|
6.50 Score on a scale
STANDARD_DEVIATION 1.350 • n=58 Participants • Here 'n' = number of evaluable participants at the specified time point
|
6.34 Score on a scale
STANDARD_DEVIATION 1.392 • n=57 Participants • Here 'n' = number of evaluable participants at the specified time point
|
6.37 Score on a scale
STANDARD_DEVIATION 1.445 • n=1638 Participants • Here 'n' = number of evaluable participants at the specified time point
|
PRIMARY outcome
Timeframe: Baseline up to Week 24Population: This outcome measure examined only placebo vs. fasinumab 1mg arms. Here, "Number of Subjects Analysed" signifies those subjects who were evaluable for this endpoint. Modified full analysis set (mFAS) includes all randomized participants in FAS but excludes participants from 4 sites for which there were potential concerns regarding data quality, identified prior to database lock.
WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in past 48 hours. It was calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (higher pain), where higher scores indicated higher pain.
Outcome measures
| Measure |
Placebo
n=208 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
n=439 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo
FAS
|
-2.21 Score on a Scale
Standard Error 0.165
|
-2.84 Score on a Scale
Standard Error 0.127
|
—
|
|
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo
mFAS
|
-2.01 Score on a Scale
Standard Error 0.182
|
-2.78 Score on a Scale
Standard Error 0.141
|
—
|
PRIMARY outcome
Timeframe: Baseline up to Week 24Population: This outcome measure examined only placebo vs. fasinumab 1mg arms. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this endpoint. The modified full analysis set (mFAS) includes all randomized participants in the FAS but excludes participants from four sites for which there were potential concerns regarding data quality, identified prior to database lock.
Physical function referred to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale was a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated maximum difficulty.
Outcome measures
| Measure |
Placebo
n=208 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
n=439 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo
FAS
|
-2.02 Score on a Scale
Standard Error 0.164
|
-2.65 Score on a Scale
Standard Error 0.125
|
—
|
|
Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo
mFAS
|
-1.80 Score on a Scale
Standard Error 0.180
|
-2.62 Score on a Scale
Standard Error 0.138
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: The FAS included all randomized participants excluding participants affected by the urgent safety measure and was based on the treatment allocated (as randomized). As pre-specified in the protocol, efficacy data from participants randomized to Fasinumab 1 mg Q4W and placebo was only included in the analysis for this outcome measure.
WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It was calculated as mean of the scores from 5 individual questions scored on a NRS of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain.
Outcome measures
| Measure |
Placebo
n=308 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
n=612 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Percentage of Participants With Greater Than or Equal to (≥) 30 Percent (%) Reduction From Baseline up to Week 24 in WOMAC Pain Subscale Score in Participants Treated With Fasinumab Compared to Placebo
|
48.7 Percentage of Participants
|
59.8 Percentage of Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: This outcome measure examined only placebo vs. fasinumab 1mg arms. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this endpoint.
The PGA was a patient-rated assessment of current disease state on a 5-point Likert scale where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (Severe symptoms and inability to carry out most normal activities) and, 5 =very poor (Very severe symptoms which were intolerable and inability to carry out all normal activities). Higher score indicated severe condition.
Outcome measures
| Measure |
Placebo
n=214 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
n=440 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Change From Baseline in Patient Global Assessment (PGA) Score up to Week 24 in Participants Treated With Fasinumab Compared to Placebo
|
-0.66 Score on a Scale
Standard Error 0.063
|
-0.81 Score on a Scale
Standard Error 0.047
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: This outcome measure examined only NSAIDs vs. fasinumab 1mg arms. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this endpoint. The modified full analysis set (mFAS) includes all randomized participants in the FAS but excludes participants from four sites for which there were potential concerns regarding data quality, identified prior to database lock.
WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a NRS of 0 (no pain) to 10 (higher pain), where higher scores indicated higher pain.
Outcome measures
| Measure |
Placebo
n=426 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
n=439 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Change From Baseline in WOMAC Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs
FAS
|
-2.60 Score on a Scale
Standard Error 0.128
|
-2.84 Score on a Scale
Standard Error 0.127
|
—
|
|
Change From Baseline in WOMAC Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs
mFAS
|
-2.48 Score on a Scale
Standard Error 0.140
|
-2.78 Score on a Scale
Standard Error 0.141
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: This outcome measure examined only NSAIDs vs. fasinumab 1mg arms. Here, "Number of Subjects Analysed" signifies those subjects who were evaluable for this endpoint. The modified full analysis set (mFAS) includes all randomized participants in the FAS but excludes participants from four sites for which there were potential concerns regarding data quality, identified prior to database lock.
Physical function referred to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale was a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated maximum difficulty.
Outcome measures
| Measure |
Placebo
n=426 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
n=439 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs
FAS
|
-2.33 Score on a Scale
Standard Error 0.127
|
-2.65 Score on a Scale
Standard Error 0.125
|
—
|
|
Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs
mFAS
|
-2.26 Score on a Scale
Standard Error 0.140
|
-2.62 Score on a Scale
Standard Error 0.138
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: This outcome measure examined only NSAIDs vs. fasinumab 1mg arms. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this endpoint.
The PGA was a patient-rated assessment of current disease state on a 5-point Likert scale where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (Severe symptoms and inability to carry out most normal activities) and, 5 =very poor (Very severe symptoms which were intolerable and inability to carry out all normal activities). Higher score indicated severe condition.
Outcome measures
| Measure |
Placebo
n=427 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
n=440 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Change From Baseline in PGA Score up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs
|
-0.75 Score on a Scale
Standard Error 0.048
|
-0.81 Score on a Scale
Standard Error 0.047
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this endpoint.
Participants reported weekly average walking index joint pain based on NRS. The NRS was nationally recognized numeric scale from 0 to 10, where 0 would demonstrate no pain, 1 to 3 would demonstrate mild pain, 4 to 6 would be moderate pain, 7 to 9 would be severe pain and 10 would be the worst pain possible. Higher score indicated greater pain.
Outcome measures
| Measure |
Placebo
n=231 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
n=449 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
n=470 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Change From Baseline in Weekly Average Walking Index Joint Pain Score up to Week 24 by Using the Numeric Rating Scale (NRS) Pain Scale
|
-1.85 Score on a Scale
Standard Error 0.130
|
-2.13 Score on a Scale
Standard Error 0.101
|
-2.51 Score on a Scale
Standard Error 0.100
|
SECONDARY outcome
Timeframe: Baseline up to follow-up period (Week 44)Population: This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. Safety Analysis set (SAF) included all randomized participants from the FAS who received any study drug. It was based on the actual treatment received.
AA was a composite term that encompasses the following conditions: Rapidly progressive Osteoarthritis (OA) type 1 and 2, Subchondral insufficiency fractures, and Primary Osteonecrosis confirmed by an arthropathy adjudication committee. AAs were also evaluated to determine if they met Destructive Arthropathy criteria.
Outcome measures
| Measure |
Placebo
n=309 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
n=609 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
n=609 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Number of Participants With Adjudicated Arthropathy (AA) Events
|
5 Participants
|
9 Participants
|
34 Participants
|
SECONDARY outcome
Timeframe: Baseline up to follow-up period (Week 44)Population: This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. SAF included all randomized participants from the FAS who received any study drug. It was based on the actual treatment received. Here, "Number of Participants Analyzed" signifies those participants who had positive AA.
DA is a unique clinical form of rapidly destructive arthropathy over and above that seen in the normal progression of OA. DA criteria can be associated with Rapidly Progressive OA type 2, Subchondral Insufficiency fracture, and Primary Osteonecrosis confirmed by an arthropathy adjudication committee.
Outcome measures
| Measure |
Placebo
n=5 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
n=9 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
n=34 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Number of Participants With AA Events Meeting Destructive Arthropathy (DA) Criteria
|
0 Participants
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Baseline up to follow-up period (Week 44)Population: This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. SAF included all randomized participants from the FAS who received any study drug. It was based on the actual treatment received.
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. TEAE was defined as an AE with an onset that occurs after receiving study drug. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious TEAEs.
Outcome measures
| Measure |
Placebo
n=309 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
n=609 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
n=609 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
|
186 Participants
|
406 Participants
|
403 Participants
|
SECONDARY outcome
Timeframe: Baseline up to follow-up period (Week 44)Population: This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. SAF included all randomized participants from the FAS who received any study drug. It was based on the actual treatment received.
Potential events of SNS dysfunction were monitored throughout the study through physical examination, AE reporting, assessment of orthostatic hypotension, and the Survey of Autonomic Symptoms. Sympathetic nervous system dysfunction was diagnosed after consultation with an appropriate specialist, such as a neurologist and/or cardiologist.
Outcome measures
| Measure |
Placebo
n=309 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
n=609 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
n=609 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Number of Participants With Sympathetic Nervous System (SNS) Dysfunction Events
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 44Population: This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. SAF included all randomized participants from the FAS who received any study drug. It is based on the actual treatment received
Any participants with a peripheral sensory event that persisted for 2 months was referred for a neurology or other specialty consultation and reported as an Adverse Events of Special Interest (AESI).
Outcome measures
| Measure |
Placebo
n=309 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
n=609 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
n=609 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Number of Participants With At-least One Peripheral Sensory Adverse Events (AEs)
|
8 Participants
|
24 Participants
|
31 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. SAF included all randomized participants from the FAS who received any study drug. It is based on the actual treatment received.
Number of participants who underwent a JR surgery from baseline up to Week 24 were reported.
Outcome measures
| Measure |
Placebo
n=309 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
n=609 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
n=609 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 24
|
2 Participants
|
7 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 44Population: This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. SAF included all randomized participants from the FAS who received any study drug. It is based on the actual treatment received.
Number of participants who underwent a JR surgery from baseline up to follow-up period (Week 44) were reported.
Outcome measures
| Measure |
Placebo
n=309 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
n=609 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
n=609 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 44
|
6 Participants
|
13 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: At Week 72Population: This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. SAF included all randomized participants from the FAS who received any study drug. It is based on the actual treatment received.
An EOS phone contact was conducted at Week 72 following the last dose of study drug (Week 24) to evaluate the number of participants who had undergone or were scheduled for JR surgery.
Outcome measures
| Measure |
Placebo
n=309 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
n=609 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
n=609 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Number of Participants With Joint Replacement (JR) Surgery Reported at End of Study (EOS) (Week 72)
|
11 Participants
|
29 Participants
|
21 Participants
|
SECONDARY outcome
Timeframe: At Weeks 0, 4, 8, 16, 24 and 44Population: Pharmacokinetic (PK) analysis set included all treated participants who received any study drug and who had at least 1 non-missing drug concentration result following the first study dose. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome measure and "Number Analyzed" = participants who were evaluable at specified time points. Data was planned to be collected and analyzed for Fasinumab 1 mg Q4W arm only.
Outcome measures
| Measure |
Placebo
n=586 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Serum Concentrations of Functional Fasinumab
Week 0
|
0.000155 Milligrams per Liter (mg/L)
Standard Deviation 0.002
|
—
|
—
|
|
Serum Concentrations of Functional Fasinumab
Week 4
|
0.0469 Milligrams per Liter (mg/L)
Standard Deviation 0.0179
|
—
|
—
|
|
Serum Concentrations of Functional Fasinumab
Week 8
|
0.0644 Milligrams per Liter (mg/L)
Standard Deviation 0.0275
|
—
|
—
|
|
Serum Concentrations of Functional Fasinumab
Week 16
|
0.0738 Milligrams per Liter (mg/L)
Standard Deviation 0.0380
|
—
|
—
|
|
Serum Concentrations of Functional Fasinumab
Week 24
|
0.0713 Milligrams per Liter (mg/L)
Standard Deviation 0.0379
|
—
|
—
|
|
Serum Concentrations of Functional Fasinumab
Week 44
|
0.000349 Milligrams per Liter (mg/L)
Standard Deviation 0.00476
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 44Population: This outcome measure examined only placebo, NSAIDs vs. fasinumab 1mg arms. The ADA analysis set included all participants who received any study drug and had at least 1 non-missing ADA result following the first dose of study drug.
Immunogenicity was characterized by ADA responses \& titers. Responses categories: Pre-existing immunoreactivity - ADA positive response at baseline with all post first dose negative results or positive response at baseline with all post first dose ADA responses \< 9-fold over baseline titer levels; Treatment-boosted response - positive response in the assay post first dose, \>= 9-fold over baseline titer levels, when baseline results are positive; Treatment-emergent response - ADA positive response post first dose when baseline results = negative or missing.
Outcome measures
| Measure |
Placebo
n=291 Participants
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
Fasinumab 1 mg
n=568 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 1 mg
n=569 Participants
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
|---|---|---|---|
|
Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) Development
Pre-Existing Immunoreactivity
|
10 Participants
|
9 Participants
|
15 Participants
|
|
Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) Development
Treated-Boosted Response
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) Development
Treatment-Emergent Response
|
3 Participants
|
1 Participants
|
4 Participants
|
Adverse Events
Placebo
Serious events: 20 serious events
Other events: 121 other events
Deaths: 1 deaths
NSAIDs
Serious events: 45 serious events
Other events: 263 other events
Deaths: 3 deaths
Fasinumab 1mg Q4W
Serious events: 35 serious events
Other events: 261 other events
Deaths: 1 deaths
Fasinumab 3mg Q4W
Serious events: 5 serious events
Other events: 17 other events
Deaths: 0 deaths
Fasinumab 6mg Q8W
Serious events: 2 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=309 participants at risk
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
NSAIDs
n=609 participants at risk
Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks.
|
Fasinumab 1mg Q4W
n=609 participants at risk
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 3mg Q4W
n=58 participants at risk
Participants received SC injection of Fasinumab at a dose of 3 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 6mg Q8W
n=59 participants at risk
Participants received SC injection of Fasinumab at a dose of 6 mg Q8W up to 24 weeks, alternating with Q8W placebo injections. Participants received placebo injections at the Q4W study visits where study drug was not administered and NSAID-matching placebo oral, BID
|
|---|---|---|---|---|---|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Cardiac disorders
Atrial fibrillation
|
0.32%
1/309 • Number of events 1 • First dose to week 44
|
0.33%
2/609 • Number of events 2 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Ear and labyrinth disorders
Vertigo positional
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Eye disorders
Retinal detachment
|
0.32%
1/309 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.33%
2/609 • Number of events 2 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.32%
1/309 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Infections and infestations
Cellulitis
|
0.00%
0/309 • First dose to week 44
|
0.33%
2/609 • Number of events 2 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Infections and infestations
Peritonsillar abscess
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Infections and infestations
Wound infection staphylococcal
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Injury, poisoning and procedural complications
Concussion
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.32%
1/309 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Injury, poisoning and procedural complications
Fractured sacrum
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Injury, poisoning and procedural complications
Multiple injuries
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
1.7%
1/58 • Number of events 2 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.97%
3/309 • Number of events 3 • First dose to week 44
|
0.99%
6/609 • Number of events 6 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
1.7%
1/58 • Number of events 1 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Musculoskeletal and connective tissue disorders
Osteoporotic fracture
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Musculoskeletal and connective tissue disorders
Rapidly progressive osteoarthritis
|
0.65%
2/309 • Number of events 2 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
1.3%
8/609 • Number of events 9 • First dose to week 44
|
3.4%
2/58 • Number of events 2 • First dose to week 44
|
3.4%
2/59 • Number of events 2 • First dose to week 44
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.00%
0/309 • First dose to week 44
|
0.33%
2/609 • Number of events 2 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Musculoskeletal and connective tissue disorders
Spinal synovial cyst
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/309 • First dose to week 44
|
0.33%
2/609 • Number of events 2 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Nervous system disorders
Amnesia
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/309 • First dose to week 44
|
0.33%
2/609 • Number of events 2 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Nervous system disorders
Dizziness
|
0.32%
1/309 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Nervous system disorders
Presyncope
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Nervous system disorders
Trigeminal neuralgia
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Product Issues
Device loosening
|
0.32%
1/309 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Reproductive system and breast disorders
Endometrial hyperplasia
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Reproductive system and breast disorders
Uterine prolapse
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.32%
1/309 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Surgical and medical procedures
Joint arthroplasty
|
0.32%
1/309 • Number of events 1 • First dose to week 44
|
0.49%
3/609 • Number of events 3 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Surgical and medical procedures
Knee arthroplasty
|
0.32%
1/309 • Number of events 1 • First dose to week 44
|
0.66%
4/609 • Number of events 4 • First dose to week 44
|
0.33%
2/609 • Number of events 3 • First dose to week 44
|
1.7%
1/58 • Number of events 1 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Vascular disorders
Arteriosclerosis
|
0.32%
1/309 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Vascular disorders
Hypertensive crisis
|
0.32%
1/309 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Vascular disorders
Varicose vein
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Cardiac disorders
Acute myocardial infarction
|
0.32%
1/309 • Number of events 1 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Cardiac disorders
Atrioventricular block complete
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
1.7%
1/58 • Number of events 1 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Gastrointestinal disorders
Diverticulum intestinal haemorrhagic
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Gastrointestinal disorders
Large intestine polyp
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 2 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
General disorders
Impaired healing
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Infections and infestations
Atypical pneumonia
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Infections and infestations
COVID-19 pneumonia
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Infections and infestations
Influenza
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Infections and infestations
Lower respiratory tract infection
|
0.32%
1/309 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Infections and infestations
Meningitis viral
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.32%
1/309 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Injury, poisoning and procedural complications
Tendon injury
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Musculoskeletal and connective tissue disorders
Joint range of motion decreased
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Musculoskeletal and connective tissue disorders
Spinal stenosis
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Musculoskeletal and connective tissue disorders
Subchondral insufficiency fracture
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
1.7%
1/58 • Number of events 1 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive papillary breast carcinoma
|
0.00%
0/309 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Nervous system disorders
Pseudostroke
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Product Issues
Device dislocation
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Psychiatric disorders
Depressed mood
|
0.32%
1/309 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.32%
1/309 • Number of events 1 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Reproductive system and breast disorders
Breast cyst
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Surgical and medical procedures
Hip arthroplasty
|
0.32%
1/309 • Number of events 1 • First dose to week 44
|
0.49%
3/609 • Number of events 3 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
|
Vascular disorders
Hypertension
|
0.00%
0/309 • First dose to week 44
|
0.00%
0/609 • First dose to week 44
|
0.16%
1/609 • Number of events 1 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
0.00%
0/59 • First dose to week 44
|
Other adverse events
| Measure |
Placebo
n=309 participants at risk
Participants who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
|
NSAIDs
n=609 participants at risk
Participants received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks.
|
Fasinumab 1mg Q4W
n=609 participants at risk
Participants received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 3mg Q4W
n=58 participants at risk
Participants received SC injection of Fasinumab at a dose of 3 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
|
Fasinumab 6mg Q8W
n=59 participants at risk
Participants received SC injection of Fasinumab at a dose of 6 mg Q8W up to 24 weeks, alternating with Q8W placebo injections. Participants received placebo injections at the Q4W study visits where study drug was not administered and NSAID-matching placebo oral, BID
|
|---|---|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
7.1%
22/309 • Number of events 26 • First dose to week 44
|
6.2%
38/609 • Number of events 44 • First dose to week 44
|
4.8%
29/609 • Number of events 35 • First dose to week 44
|
3.4%
2/58 • Number of events 2 • First dose to week 44
|
1.7%
1/59 • Number of events 1 • First dose to week 44
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.7%
36/309 • Number of events 53 • First dose to week 44
|
12.8%
78/609 • Number of events 102 • First dose to week 44
|
13.5%
82/609 • Number of events 109 • First dose to week 44
|
6.9%
4/58 • Number of events 7 • First dose to week 44
|
5.1%
3/59 • Number of events 3 • First dose to week 44
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.5%
17/309 • Number of events 17 • First dose to week 44
|
7.2%
44/609 • Number of events 60 • First dose to week 44
|
7.6%
46/609 • Number of events 51 • First dose to week 44
|
1.7%
1/58 • Number of events 1 • First dose to week 44
|
1.7%
1/59 • Number of events 1 • First dose to week 44
|
|
Infections and infestations
Upper respiratory tract infection
|
4.9%
15/309 • Number of events 18 • First dose to week 44
|
4.9%
30/609 • Number of events 31 • First dose to week 44
|
4.9%
30/609 • Number of events 33 • First dose to week 44
|
5.2%
3/58 • Number of events 3 • First dose to week 44
|
1.7%
1/59 • Number of events 1 • First dose to week 44
|
|
Investigations
Blood creatine phosphokinase increased
|
0.97%
3/309 • Number of events 3 • First dose to week 44
|
0.82%
5/609 • Number of events 5 • First dose to week 44
|
0.82%
5/609 • Number of events 5 • First dose to week 44
|
5.2%
3/58 • Number of events 3 • First dose to week 44
|
5.1%
3/59 • Number of events 3 • First dose to week 44
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
0.65%
2/309 • Number of events 2 • First dose to week 44
|
0.66%
4/609 • Number of events 4 • First dose to week 44
|
0.82%
5/609 • Number of events 5 • First dose to week 44
|
0.00%
0/58 • First dose to week 44
|
5.1%
3/59 • Number of events 3 • First dose to week 44
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.00%
0/309 • First dose to week 44
|
0.66%
4/609 • Number of events 5 • First dose to week 44
|
0.99%
6/609 • Number of events 7 • First dose to week 44
|
5.2%
3/58 • Number of events 3 • First dose to week 44
|
1.7%
1/59 • Number of events 1 • First dose to week 44
|
|
Nervous system disorders
Headache
|
15.5%
48/309 • Number of events 113 • First dose to week 44
|
17.6%
107/609 • Number of events 210 • First dose to week 44
|
15.6%
95/609 • Number of events 224 • First dose to week 44
|
3.4%
2/58 • Number of events 2 • First dose to week 44
|
3.4%
2/59 • Number of events 2 • First dose to week 44
|
|
Infections and infestations
Urinary tract infection
|
8.1%
25/309 • Number of events 29 • First dose to week 44
|
5.7%
35/609 • Number of events 39 • First dose to week 44
|
8.2%
50/609 • Number of events 57 • First dose to week 44
|
1.7%
1/58 • Number of events 1 • First dose to week 44
|
3.4%
2/59 • Number of events 2 • First dose to week 44
|
Additional Information
Clinical Trials Administrator
Regeneron Pharmaceuticals, Inc.
Phone: 844-734-6643
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
- Publication restrictions are in place
Restriction type: OTHER