Trial Outcomes & Findings for Safety and Bone Health Study of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis (NCT NCT03727022)
NCT ID: NCT03727022
Last Updated: 2026-01-12
Results Overview
Evaluate change in total bone mineral density (BMD) from baseline in the treated knee compared to placebo by quantitative computed tomography (qCT)
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
101 participants
Primary outcome timeframe
Baseline and Week 52
Results posted on
2026-01-12
Participant Flow
Participant milestones
| Measure |
Vehicle
Intra-articular injections of 0 mg SM04690 in 2 mL vehicle
Placebo: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
0.07 mg SM04690
Intra-articular injections of 0.07 mg SM04690 in 2 mL vehicle
SM04690: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
|---|---|---|
|
Phase A
STARTED
|
50
|
51
|
|
Phase A
COMPLETED
|
38
|
39
|
|
Phase A
NOT COMPLETED
|
12
|
12
|
|
Phase B
STARTED
|
32
|
33
|
|
Phase B
COMPLETED
|
24
|
29
|
|
Phase B
NOT COMPLETED
|
8
|
4
|
Reasons for withdrawal
| Measure |
Vehicle
Intra-articular injections of 0 mg SM04690 in 2 mL vehicle
Placebo: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
0.07 mg SM04690
Intra-articular injections of 0.07 mg SM04690 in 2 mL vehicle
SM04690: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
|---|---|---|
|
Phase A
Lost to Follow-up
|
2
|
3
|
|
Phase A
Withdrawal by Subject
|
10
|
9
|
|
Phase B
Lost to Follow-up
|
0
|
1
|
|
Phase B
Subject Non-Compliance
|
1
|
0
|
|
Phase B
Withdrawal by Subject
|
3
|
3
|
|
Phase B
Site Closure
|
4
|
0
|
Baseline Characteristics
Safety and Bone Health Study of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis
Baseline characteristics by cohort
| Measure |
Vehicle
n=50 Participants
Intra-articular injections of 0 mg SM04690 in 2 mL vehicle
Placebo: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
0.07 mg SM04690
n=51 Participants
Intra-articular injections of 0.07 mg SM04690 in 2 mL vehicle
SM04690: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
Total
n=101 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Kellgren-Lawrence Grade
Grade 2
|
31 Participants
n=210 Participants
|
22 Participants
n=19 Participants
|
53 Participants
n=8 Participants
|
|
Age, Continuous
|
60.5 years
STANDARD_DEVIATION 9.8 • n=210 Participants
|
61.3 years
STANDARD_DEVIATION 8.4 • n=19 Participants
|
60.9 years
STANDARD_DEVIATION 9.1 • n=8 Participants
|
|
Sex: Female, Male
Female
|
34 Participants
n=210 Participants
|
26 Participants
n=19 Participants
|
60 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=210 Participants
|
25 Participants
n=19 Participants
|
41 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
14 Participants
n=210 Participants
|
13 Participants
n=19 Participants
|
27 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
36 Participants
n=210 Participants
|
38 Participants
n=19 Participants
|
74 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=210 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=210 Participants
|
0 Participants
n=19 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=210 Participants
|
1 Participants
n=19 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=210 Participants
|
1 Participants
n=19 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=210 Participants
|
9 Participants
n=19 Participants
|
17 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
41 Participants
n=210 Participants
|
40 Participants
n=19 Participants
|
81 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=210 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=210 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=8 Participants
|
|
Body Mass Index
|
27.93 kg/m^2
STANDARD_DEVIATION 4.12 • n=210 Participants
|
29.30 kg/m^2
STANDARD_DEVIATION 3.02 • n=19 Participants
|
28.63 kg/m^2
STANDARD_DEVIATION 3.65 • n=8 Participants
|
|
Kellgren-Lawrence Grade
Grade 3
|
19 Participants
n=210 Participants
|
29 Participants
n=19 Participants
|
48 Participants
n=8 Participants
|
|
Medial Joint Space Width
|
3.193 mm
STANDARD_DEVIATION 1.348 • n=210 Participants
|
3.119 mm
STANDARD_DEVIATION 1.216 • n=19 Participants
|
3.156 mm
STANDARD_DEVIATION 1.277 • n=8 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 52Population: Full Analysis Set includes all subjects who received at least one study injection in Phase A. Subjects' observed data were analyzed as randomized for the FAS without imputation.
Evaluate change in total bone mineral density (BMD) from baseline in the treated knee compared to placebo by quantitative computed tomography (qCT)
Outcome measures
| Measure |
Vehicle
n=34 Participants
Intra-articular injections of 0 mg SM04690 in 2 mL vehicle
Placebo: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
0.07 mg SM04690
n=37 Participants
Intra-articular injections of 0.07 mg SM04690 in 2 mL vehicle
SM04690: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
|---|---|---|
|
Change in Total BMD From Baseline in the Treated Knee Compared to Placebo by qCT
|
-0.47 mg/cm^3
Standard Deviation 8.21
|
-3.32 mg/cm^3
Standard Deviation 10.00
|
SECONDARY outcome
Timeframe: Baseline and Weeks 12Population: Full Analysis Set includes all subjects who received at least one study injection in Phase A. Subjects' observed data were analyzed as randomized for the FAS without imputation.
Evaluate change in total BMD from baseline in the treated knee compared to placebo by qCT
Outcome measures
| Measure |
Vehicle
n=43 Participants
Intra-articular injections of 0 mg SM04690 in 2 mL vehicle
Placebo: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
0.07 mg SM04690
n=45 Participants
Intra-articular injections of 0.07 mg SM04690 in 2 mL vehicle
SM04690: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
|---|---|---|
|
Change in Total BMD From Baseline in the Treated Knee Compared to Placebo by qCT
|
-0.38 mg/cm^3
Standard Deviation 7.89
|
-0.34 mg/cm^3
Standard Deviation 7.28
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: Full Analysis Set includes all subjects who received at least one study injection in Phase A. Subjects' observed data were analyzed as randomized for the FAS without imputation.
Evaluate change in total BMD from baseline in the treated knee compared to placebo by qCT
Outcome measures
| Measure |
Vehicle
n=40 Participants
Intra-articular injections of 0 mg SM04690 in 2 mL vehicle
Placebo: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
0.07 mg SM04690
n=39 Participants
Intra-articular injections of 0.07 mg SM04690 in 2 mL vehicle
SM04690: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
|---|---|---|
|
Change in Total BMD From Baseline in the Treated Knee Compared to Placebo by qCT
|
1.34 mg/cm^3
Standard Deviation 7.77
|
-0.76 mg/cm^3
Standard Deviation 8.81
|
SECONDARY outcome
Timeframe: Baseline and Week 36Population: Full Analysis Set includes all subjects who received at least one study injection in Phase A. Subjects' observed data were analyzed as randomized for the FAS without imputation.
Evaluate change in total BMD from baseline in the treated knee compared to placebo by qCT
Outcome measures
| Measure |
Vehicle
n=36 Participants
Intra-articular injections of 0 mg SM04690 in 2 mL vehicle
Placebo: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
0.07 mg SM04690
n=33 Participants
Intra-articular injections of 0.07 mg SM04690 in 2 mL vehicle
SM04690: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
|---|---|---|
|
Change in Total BMD From Baseline in the Treated Knee Compared to Placebo by qCT
|
-1.82 mg/cm^3
Standard Deviation 8.47
|
-2.06 mg/cm^3
Standard Deviation 7.18
|
SECONDARY outcome
Timeframe: Baseline and Week 64Population: Full Analysis Set (FASB) includes all subjects who received at least one study injection in Phase B. Subjects' observed data were analyzed as randomized for the FASB without imputation.
Evaluate change in total bone mineral density (BMD) from baseline in the treated knee compared to placebo by quantitative computed tomography (qCT)
Outcome measures
| Measure |
Vehicle
n=25 Participants
Intra-articular injections of 0 mg SM04690 in 2 mL vehicle
Placebo: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
0.07 mg SM04690
n=30 Participants
Intra-articular injections of 0.07 mg SM04690 in 2 mL vehicle
SM04690: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
|---|---|---|
|
Change in Total BMD From Baseline in the Treated Knee Compared to Placebo by qCT
|
-4.56 mg/cm^3
Standard Deviation 9.84
|
-3.76 mg/cm^3
Standard Deviation 9.94
|
SECONDARY outcome
Timeframe: Baseline and Week 76Population: Full Analysis Set (FASB) includes all subjects who received at least one study injection in Phase B. Subjects' observed data were analyzed as randomized for the FASB without imputation.
Evaluate change in total BMD from baseline in the treated knee compared to placebo by qCT
Outcome measures
| Measure |
Vehicle
n=25 Participants
Intra-articular injections of 0 mg SM04690 in 2 mL vehicle
Placebo: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
0.07 mg SM04690
n=30 Participants
Intra-articular injections of 0.07 mg SM04690 in 2 mL vehicle
SM04690: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
|---|---|---|
|
Change in Total BMD From Baseline in the Treated Knee Compared to Placebo by qCT
|
-2.13 mg/cm^3
Standard Deviation 8.94
|
-5.61 mg/cm^3
Standard Deviation 10.67
|
SECONDARY outcome
Timeframe: Baseline and Week 88Population: Full Analysis Set (FASB) includes all subjects who received at least one study injection in Phase B. Subjects' observed data were analyzed as randomized for the FASB without imputation.
Evaluate change in total BMD from baseline in the treated knee compared to placebo by qCT
Outcome measures
| Measure |
Vehicle
n=23 Participants
Intra-articular injections of 0 mg SM04690 in 2 mL vehicle
Placebo: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
0.07 mg SM04690
n=28 Participants
Intra-articular injections of 0.07 mg SM04690 in 2 mL vehicle
SM04690: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
|---|---|---|
|
Change in Total BMD From Baseline in the Treated Knee Compared to Placebo by qCT
|
-2.59 mg/cm^3
Standard Deviation 10.52
|
-5.14 mg/cm^3
Standard Deviation 11.59
|
SECONDARY outcome
Timeframe: Baseline and Week 104Population: Full Analysis Set (FASB) includes all subjects who received at least one study injection in Phase B. Subjects' observed data were analyzed as randomized for the FASB without imputation.
Evaluate change in total BMD from baseline in the treated knee compared to placebo by qCT
Outcome measures
| Measure |
Vehicle
n=24 Participants
Intra-articular injections of 0 mg SM04690 in 2 mL vehicle
Placebo: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
0.07 mg SM04690
n=29 Participants
Intra-articular injections of 0.07 mg SM04690 in 2 mL vehicle
SM04690: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
|---|---|---|
|
Change in Total BMD From Baseline in the Treated Knee Compared to Placebo by qCT
|
-2.95 mg/cm^3
Standard Deviation 13.21
|
-7.08 mg/cm^3
Standard Deviation 12.34
|
Adverse Events
0.07 mg SM04690
Serious events: 2 serious events
Other events: 11 other events
Deaths: 0 deaths
Vehicle
Serious events: 2 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
0.07 mg SM04690
n=51 participants at risk
Intra-articular injections of 0.07 mg SM04690 in 2 mL vehicle
SM04690: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
Vehicle
n=50 participants at risk
Intra-articular injections of 0 mg SM04690 in 2 mL vehicle
Placebo: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/51 • Baseline to End of Study Visit at Week 104 (2 years)
|
2.0%
1/50 • Number of events 1 • Baseline to End of Study Visit at Week 104 (2 years)
|
|
Cardiac disorders
Nodal rhythm
|
0.00%
0/51 • Baseline to End of Study Visit at Week 104 (2 years)
|
2.0%
1/50 • Number of events 1 • Baseline to End of Study Visit at Week 104 (2 years)
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/51 • Baseline to End of Study Visit at Week 104 (2 years)
|
2.0%
1/50 • Number of events 1 • Baseline to End of Study Visit at Week 104 (2 years)
|
|
Injury, poisoning and procedural complications
Procedural pneumothorax
|
0.00%
0/51 • Baseline to End of Study Visit at Week 104 (2 years)
|
2.0%
1/50 • Number of events 1 • Baseline to End of Study Visit at Week 104 (2 years)
|
|
Gastrointestinal disorders
Gastric ulcer
|
2.0%
1/51 • Number of events 1 • Baseline to End of Study Visit at Week 104 (2 years)
|
0.00%
0/50 • Baseline to End of Study Visit at Week 104 (2 years)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hormone receptor positive breast cancer
|
2.0%
1/51 • Number of events 1 • Baseline to End of Study Visit at Week 104 (2 years)
|
0.00%
0/50 • Baseline to End of Study Visit at Week 104 (2 years)
|
|
Nervous system disorders
Intracranial aneurysm
|
2.0%
1/51 • Number of events 1 • Baseline to End of Study Visit at Week 104 (2 years)
|
0.00%
0/50 • Baseline to End of Study Visit at Week 104 (2 years)
|
|
Cardiac disorders
Aortic valve incompetence
|
0.00%
0/51 • Baseline to End of Study Visit at Week 104 (2 years)
|
2.0%
1/50 • Number of events 1 • Baseline to End of Study Visit at Week 104 (2 years)
|
Other adverse events
| Measure |
0.07 mg SM04690
n=51 participants at risk
Intra-articular injections of 0.07 mg SM04690 in 2 mL vehicle
SM04690: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
Vehicle
n=50 participants at risk
Intra-articular injections of 0 mg SM04690 in 2 mL vehicle
Placebo: Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)
|
|---|---|---|
|
Investigations
Blood pressure increased
|
7.8%
4/51 • Number of events 4 • Baseline to End of Study Visit at Week 104 (2 years)
|
2.0%
1/50 • Number of events 2 • Baseline to End of Study Visit at Week 104 (2 years)
|
|
Infections and infestations
Sinusitis
|
5.9%
3/51 • Number of events 4 • Baseline to End of Study Visit at Week 104 (2 years)
|
2.0%
1/50 • Number of events 1 • Baseline to End of Study Visit at Week 104 (2 years)
|
|
Infections and infestations
COVID-19
|
3.9%
2/51 • Number of events 2 • Baseline to End of Study Visit at Week 104 (2 years)
|
0.00%
0/50 • Baseline to End of Study Visit at Week 104 (2 years)
|
|
Infections and infestations
Influenza
|
3.9%
2/51 • Number of events 2 • Baseline to End of Study Visit at Week 104 (2 years)
|
0.00%
0/50 • Baseline to End of Study Visit at Week 104 (2 years)
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
3.9%
2/51 • Number of events 2 • Baseline to End of Study Visit at Week 104 (2 years)
|
0.00%
0/50 • Baseline to End of Study Visit at Week 104 (2 years)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.0%
1/51 • Number of events 1 • Baseline to End of Study Visit at Week 104 (2 years)
|
10.0%
5/50 • Number of events 5 • Baseline to End of Study Visit at Week 104 (2 years)
|
|
Infections and infestations
Nasopharyngitis
|
2.0%
1/51 • Number of events 1 • Baseline to End of Study Visit at Week 104 (2 years)
|
4.0%
2/50 • Number of events 2 • Baseline to End of Study Visit at Week 104 (2 years)
|
|
Ear and labyrinth disorders
Cerumen impaction
|
0.00%
0/51 • Baseline to End of Study Visit at Week 104 (2 years)
|
4.0%
2/50 • Number of events 2 • Baseline to End of Study Visit at Week 104 (2 years)
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/51 • Baseline to End of Study Visit at Week 104 (2 years)
|
4.0%
2/50 • Number of events 2 • Baseline to End of Study Visit at Week 104 (2 years)
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/51 • Baseline to End of Study Visit at Week 104 (2 years)
|
4.0%
2/50 • Number of events 3 • Baseline to End of Study Visit at Week 104 (2 years)
|
Additional Information
Christopher Swearingen, PhD, VP of Biometrics
Biosplice Therapeutics
Phone: 858.926.2900
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee There is an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
- Publication restrictions are in place
Restriction type: OTHER