Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of EP-104IAR in Patients With Osteoarthritis of the Knee (NCT NCT04120402)
NCT ID: NCT04120402
Last Updated: 2024-06-25
Results Overview
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (scores scaled 0-10, with 10 being the worst). Least squares mean from a mixed model for repeated measures (MMRM) for change from baseline with fixed effects for site, treatment, week, treatment-by-week interaction; random effect for subject; and covariate baseline WOMAC pain score.
COMPLETED
PHASE2
318 participants
12 weeks
2024-06-25
Participant Flow
Participant milestones
| Measure |
EP-104IAR 25 mg
A single use intra-articular injection containing 25 mg of EP-104IAR
EP-104IAR 25 mg: Single 5 mL intra-articular injection
|
Placebo (Vehicle)
A single use intra-articular injection containing no active ingredients
Vehicle: Single 5 mL intra-articular injection
|
|---|---|---|
|
Overall Study
STARTED
|
163
|
155
|
|
Overall Study
COMPLETED
|
156
|
148
|
|
Overall Study
NOT COMPLETED
|
7
|
7
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The analysis population is the intent to treat population of 318 patients in total. Out of the 318 patients 163 patients were in the EP-104IAR 25mg arm and 155 patients were in the Placebo (Vehicle) arm.
Baseline characteristics by cohort
| Measure |
EP-104IAR 25 mg
n=163 Participants
A single use intra-articular injection containing 25 mg of EP-104IAR
EP-104IAR 25 mg: Single 5 mL intra-articular injection
|
Placebo (Vehicle)
n=155 Participants
A single use intra-articular injection containing no active ingredients
Vehicle: Single 5 mL intra-articular injection
|
Total
n=318 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants • The analysis population is the intent to treat population of 318 patients in total. Out of the 318 patients 163 patients were in the EP-104IAR 25mg arm and 155 patients were in the Placebo (Vehicle) arm.
|
0 Participants
n=107 Participants • The analysis population is the intent to treat population of 318 patients in total. Out of the 318 patients 163 patients were in the EP-104IAR 25mg arm and 155 patients were in the Placebo (Vehicle) arm.
|
0 Participants
n=206 Participants • The analysis population is the intent to treat population of 318 patients in total. Out of the 318 patients 163 patients were in the EP-104IAR 25mg arm and 155 patients were in the Placebo (Vehicle) arm.
|
|
Age, Categorical
Between 18 and 65 years
|
91 Participants
n=99 Participants • The analysis population is the intent to treat population of 318 patients in total. Out of the 318 patients 163 patients were in the EP-104IAR 25mg arm and 155 patients were in the Placebo (Vehicle) arm.
|
89 Participants
n=107 Participants • The analysis population is the intent to treat population of 318 patients in total. Out of the 318 patients 163 patients were in the EP-104IAR 25mg arm and 155 patients were in the Placebo (Vehicle) arm.
|
180 Participants
n=206 Participants • The analysis population is the intent to treat population of 318 patients in total. Out of the 318 patients 163 patients were in the EP-104IAR 25mg arm and 155 patients were in the Placebo (Vehicle) arm.
|
|
Age, Categorical
>=65 years
|
72 Participants
n=99 Participants • The analysis population is the intent to treat population of 318 patients in total. Out of the 318 patients 163 patients were in the EP-104IAR 25mg arm and 155 patients were in the Placebo (Vehicle) arm.
|
66 Participants
n=107 Participants • The analysis population is the intent to treat population of 318 patients in total. Out of the 318 patients 163 patients were in the EP-104IAR 25mg arm and 155 patients were in the Placebo (Vehicle) arm.
|
138 Participants
n=206 Participants • The analysis population is the intent to treat population of 318 patients in total. Out of the 318 patients 163 patients were in the EP-104IAR 25mg arm and 155 patients were in the Placebo (Vehicle) arm.
|
|
Age, Continuous
|
64.0 years
STANDARD_DEVIATION 9.31 • n=99 Participants
|
63.2 years
STANDARD_DEVIATION 9.37 • n=107 Participants
|
63.6 years
STANDARD_DEVIATION 9.33 • n=206 Participants
|
|
Sex: Female, Male
Female
|
94 Participants
n=99 Participants
|
89 Participants
n=107 Participants
|
183 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
69 Participants
n=99 Participants
|
66 Participants
n=107 Participants
|
135 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
161 Participants
n=99 Participants
|
152 Participants
n=107 Participants
|
313 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
162 Participants
n=99 Participants
|
153 Participants
n=107 Participants
|
315 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
Czechia
|
40 participants
n=99 Participants
|
35 participants
n=107 Participants
|
75 participants
n=206 Participants
|
|
Region of Enrollment
Denmark
|
85 participants
n=99 Participants
|
84 participants
n=107 Participants
|
169 participants
n=206 Participants
|
|
Region of Enrollment
Poland
|
38 participants
n=99 Participants
|
36 participants
n=107 Participants
|
74 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: The intention-to-treat (ITT) population consists of all subjects who were both randomized to and received treatment. Analysis was conducted allocating subjects to the treatment to which they were randomized, irrespective of what was actually received.
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (scores scaled 0-10, with 10 being the worst). Least squares mean from a mixed model for repeated measures (MMRM) for change from baseline with fixed effects for site, treatment, week, treatment-by-week interaction; random effect for subject; and covariate baseline WOMAC pain score.
Outcome measures
| Measure |
EP-104IAR 25 mg
n=163 Participants
A single use intra-articular injection containing 25 mg of EP-104IAR
EP-104IAR 25 mg: Single 5 mL intra-articular injection
|
Placebo (Vehicle)
n=155 Participants
A single use intra-articular injection containing no active ingredients
Vehicle: Single 5 mL intra-articular injection
|
|---|---|---|
|
Difference in Change From Baseline Between EP-104IAR and Vehicle in WOMAC Pain Subscale
|
-2.89 score on a scale
Standard Error 0.166
|
-2.23 score on a scale
Standard Error 0.171
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: The intention-to-treat (ITT) population consists of all subjects who were both randomized to and received treatment. Analysis was conducted allocating subjects to the treatment to which they were randomized, irrespective of what was actually received.
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function subscale (scores scaled 0-10, with 10 being the worst). Function subscale includes questions related to the physical functioning of osteoarthritis e.g. stair use, standing, walking etc. From a mixed model for repeated measures (MMRM) for change from baseline with fixed effects for site, treatment, week, treatment-by-week interaction; random effect for subject; and covariate baseline WOMAC function score.
Outcome measures
| Measure |
EP-104IAR 25 mg
n=163 Participants
A single use intra-articular injection containing 25 mg of EP-104IAR
EP-104IAR 25 mg: Single 5 mL intra-articular injection
|
Placebo (Vehicle)
n=155 Participants
A single use intra-articular injection containing no active ingredients
Vehicle: Single 5 mL intra-articular injection
|
|---|---|---|
|
Difference in Change From Baseline Between EP-104IAR and Vehicle in WOMAC Function Subscale
|
-2.59 score on a scale
Standard Error 0.161
|
-2.04 score on a scale
Standard Error 0.166
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: The intention-to-treat (ITT) population consists of all subjects who were both randomized to and received treatment. Analysis was conducted allocating subjects to the treatment to which they were randomized, irrespective of what was actually received.
Area under the curve in change from baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (scores scaled 0-10, with 10 being the worst) from Week 0 to Week 12 was calculated on a per-individual basis using the linear trapezoidal rule. AUC was normalized to account for subjects whose actual days and nominal days at Week 12 differed. Treatments were compared using an ANCOVA model containing site; individual baseline WOMAC Pain; and treatment group as covariates.
Outcome measures
| Measure |
EP-104IAR 25 mg
n=163 Participants
A single use intra-articular injection containing 25 mg of EP-104IAR
EP-104IAR 25 mg: Single 5 mL intra-articular injection
|
Placebo (Vehicle)
n=155 Participants
A single use intra-articular injection containing no active ingredients
Vehicle: Single 5 mL intra-articular injection
|
|---|---|---|
|
Difference Between EP-104IAR and Vehicle in the Area Under the Curve (AUC) of WOMAC Pain Subscale
|
-235.67 score on a scale multiplied by days
Standard Error 11.769
|
-166.78 score on a scale multiplied by days
Standard Error 12.169
|
SECONDARY outcome
Timeframe: 24 weeksPopulation: The intention-to-treat (ITT) population consists of all subjects who were both randomized to and received treatment. Analysis was conducted allocating subjects to the treatment to which they were randomized, irrespective of what was actually received.
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (scores scaled 0-10, with 10 being the worst). Least squares mean from a mixed model for repeated measures (MMRM) for change from baseline with fixed effects for site, treatment, week, treatment-by-week interaction; random effect for subject; and covariate baseline WOMAC pain score.
Outcome measures
| Measure |
EP-104IAR 25 mg
n=163 Participants
A single use intra-articular injection containing 25 mg of EP-104IAR
EP-104IAR 25 mg: Single 5 mL intra-articular injection
|
Placebo (Vehicle)
n=155 Participants
A single use intra-articular injection containing no active ingredients
Vehicle: Single 5 mL intra-articular injection
|
|---|---|---|
|
Difference in Change From Baseline Between EP-104IAR and Vehicle in WOMAC Pain Subscale
|
-2.26 score on a scale
Standard Error 0.171
|
-2.11 score on a scale
Standard Error 0.175
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: The intention-to-treat (ITT) population consists of all subjects who were both randomized to and received treatment. Analysis was conducted allocating subjects to the treatment to which they were randomized, irrespective of what was actually received.
Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) strict responders are defined as at least 50% improvement (decrease from baseline) in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain or function subscales (scores scaled 0-10, with 10 being the worst) and an absolute change of at least 2 in the respective score. Patients who discontinued prior to Week 12 were considered non-responders.
Outcome measures
| Measure |
EP-104IAR 25 mg
n=163 Participants
A single use intra-articular injection containing 25 mg of EP-104IAR
EP-104IAR 25 mg: Single 5 mL intra-articular injection
|
Placebo (Vehicle)
n=155 Participants
A single use intra-articular injection containing no active ingredients
Vehicle: Single 5 mL intra-articular injection
|
|---|---|---|
|
Difference Between EP-104IAR and Vehicle in OMERACT-OARSI Strict Responders
|
87 Participants
|
61 Participants
|
Adverse Events
EP-104IAR 25 mg
Placebo (Vehicle)
Serious adverse events
| Measure |
EP-104IAR 25 mg
n=163 participants at risk
A single use intra-articular injection containing 25 mg of EP-104IAR
EP-104IAR 25 mg: Single 5 mL intra-articular injection
|
Placebo (Vehicle)
n=155 participants at risk
A single use intra-articular injection containing no active ingredients
Vehicle: Single 5 mL intra-articular injection
|
|---|---|---|
|
Nervous system disorders
Cerebrovascular accident
|
0.61%
1/163 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
0.00%
0/155 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.61%
1/163 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
0.00%
0/155 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
|
Nervous system disorders
Loss of consciousness
|
0.61%
1/163 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
0.00%
0/155 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
|
Ear and labyrinth disorders
Acute vestibular syndrome
|
0.61%
1/163 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
0.00%
0/155 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/163 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
0.65%
1/155 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
Other adverse events
| Measure |
EP-104IAR 25 mg
n=163 participants at risk
A single use intra-articular injection containing 25 mg of EP-104IAR
EP-104IAR 25 mg: Single 5 mL intra-articular injection
|
Placebo (Vehicle)
n=155 participants at risk
A single use intra-articular injection containing no active ingredients
Vehicle: Single 5 mL intra-articular injection
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
8.6%
14/163 • Number of events 16 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
7.7%
12/155 • Number of events 15 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
|
Infections and infestations
COVID-19
|
8.6%
14/163 • Number of events 14 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
9.0%
14/155 • Number of events 14 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
|
Infections and infestations
Influenza
|
3.7%
6/163 • Number of events 6 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
5.8%
9/155 • Number of events 9 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
23.3%
38/163 • Number of events 38 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
14.8%
23/155 • Number of events 26 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
|
General disorders
Influenza like illness
|
2.5%
4/163 • Number of events 5 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
6.5%
10/155 • Number of events 10 • Treatment-emergent adverse events (TEAEs) were summarized and analyzed for safety evaluations i.e, events which occurred from the time of the EP-104IAR or vehicle injection procedure until the Week 24/End-of-Study/Early Exit Visit.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Investigators may not present or publish partial or complete study results individually without the Sponsor's agreement. Any manuscript or abstract proposed by the Investigators must be reviewed and approved in writing by the Sponsor before submission for publication. Names of all Investigators participating in the study will be included in the publication.
- Publication restrictions are in place
Restriction type: OTHER