An Observational Study Evaluating the Safety, Tolerability, and Efficacy of Treatment of SM04690 or Placebo Previously Injected in the Target Knee Joint of Subjects With Moderately to Severely Symptomatic Osteoarthritis

Adverse events (AEs) of interest

Compare the number of subjects who experience an AE of interest occurring in the (previously injected) SM04690 treatment arms to the (previously injected) placebo treatment arm at Month 6. AEs of interest include those related to either knee and/or an AE that is a newly diagnosed chronic condition requiring treatment (e.g., hypertension, hyperlipidemia, diabetes).

Time frame: Month 6

AEs of interest

Compare the number of subjects who experience an AE of interest occurring in the (previously injected) SM04690 treatment arms to the (previously injected) placebo treatment arm at Month 12.

Time frame: Month 12

AEs of interest

Compare the number of subjects who experience an AE of interest occurring in the (previously injected) SM04690 treatment arms to the (previously injected) placebo treatment arm at Month 24.

Time frame: Month 24

AEs of interest

Compare the number of subjects who experience an AE of interest occurring in the (previously injected) SM04690 treatment arms to the (previously injected) placebo treatment arm at Month 36.

Time frame: Month 36

AEs of interest

Compare the number of subjects who experience an AE of interest occurring in the (previously injected) SM04690 treatment arms to the (previously injected) placebo treatment arm at Month 48.

Time frame: Month 48

AEs of interest

Compare the number of subjects who experience an AE of interest occurring in the (previously injected) SM04690 treatment arms to the (previously injected) placebo treatment arm at Month 60.

Time frame: Month 60

Incidence and incidence rate of total knee replacement (TKR)

Compare the incidence and incidence rate of TKR in the previously injected knee occurring in the (previously injected) SM04690 treatment arms to the (previously injected) placebo treatment arm by Month 60.

Time frame: Month 60

Change in joint space width (JSW)

Change from baseline in JSW as documented by X-ray of the target knee in both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 6.

Time frame: Baseline and Month 6

Change in joint space width (JSW)

Change from baseline in JSW as documented by X-ray of the target knee in both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 12.

Time frame: Baseline and Month 12

Change in joint space width (JSW)

Change from baseline in JSW as documented by X-ray of the target knee in both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 24.

Time frame: Baseline and Month 24

Change in joint space width (JSW)

Change from baseline in JSW as documented by X-ray of the target knee in both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 36.

Time frame: Baseline and Month 36

Change in joint space width (JSW)

Change from baseline in JSW as documented by X-ray of the target knee in both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 48.

Time frame: Baseline and Month 48

Change in joint space width (JSW)

Change from baseline in JSW as documented by X-ray of the target knee in both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 60.

Time frame: Baseline and Month 60

Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score

Change from baseline in WOMAC total score for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 6.

Time frame: Baseline and Month 6

Change in WOMAC total score

Change from baseline in WOMAC total score for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 12.

Time frame: Baseline and Month 12

Change in WOMAC total score

Change from baseline in WOMAC total score for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 24.

Time frame: Baseline and Month 24

Change in WOMAC total score

Change from baseline in WOMAC total score for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 36.

Time frame: Baseline and Month 36

Change in WOMAC total score

Change from baseline in WOMAC total score for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 48.

Time frame: Baseline and Month 48

Change in WOMAC total score

Change from baseline in WOMAC total score for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 60.

Time frame: Baseline and Month 60

Change in WOMAC pain subscore

Change from baseline in WOMAC pain subscore for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 6.

Time frame: Baseline and Month 6

Change in WOMAC pain subscore

Change from baseline in WOMAC pain subscore for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 12.

Time frame: Baseline and Month 12

Change in WOMAC pain subscore

Change from baseline in WOMAC pain subscore for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 24.

Time frame: Baseline and Month 24

Change in WOMAC pain subscore

Change from baseline in WOMAC pain subscore for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 36.

Time frame: Baseline and Month 36

Change in WOMAC pain subscore

Change from baseline in WOMAC pain subscore for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 48.

Time frame: Baseline and Month 48

Change in WOMAC pain subscore

Change from baseline in WOMAC pain subscore for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 60.

Time frame: Baseline and Month 60

Change in WOMAC function subscore

Change from baseline in WOMAC function subscore for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 6.

Time frame: Baseline and Month 6

Change in WOMAC function subscore

Change from baseline in WOMAC function subscore for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 12.

Time frame: Baseline and Month 12

Change in WOMAC function subscore

Change from baseline in WOMAC function subscore for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 24.

Time frame: Baseline and Month 24

Change in WOMAC function subscore

Change from baseline in WOMAC function subscore for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 36.

Time frame: Baseline and Month 36

Change in WOMAC function subscore

Change from baseline in WOMAC function subscore for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 48.

Time frame: Baseline and Month 48

Change in WOMAC function subscore

Change from baseline in WOMAC function subscore for the target knee for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 60.

Time frame: Baseline and Month 60

Change in Physician Global Assessment

Change from baseline OA disease activity as assessed by Physician Global Assessment for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 6.

Time frame: Baseline and Month 6

Change in Physician Global Assessment

Change from baseline OA disease activity as assessed by Physician Global Assessment for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 12.

Time frame: Baseline and Month 12

Change in Physician Global Assessment

Change from baseline OA disease activity as assessed by Physician Global Assessment for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 24.

Time frame: Baseline and Month 24

Change in Physician Global Assessment

Change from baseline OA disease activity as assessed by Physician Global Assessment for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 36.

Time frame: Baseline and Month 36

Change in Physician Global Assessment

Change from baseline OA disease activity as assessed by Physician Global Assessment for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 48.

Time frame: Baseline and Month 48

Change in Physician Global Assessment

Change from baseline OA disease activity as assessed by Physician Global Assessment for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 60.

Time frame: Baseline and Month 60

Change in Patient Global Assessment

Change from baseline OA disease activity as assessed by Patient Global Assessment for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 6.

Time frame: Baseline and Month 6

Change in Patient Global Assessment

Change from baseline OA disease activity as assessed by Patient Global Assessment for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 12.

Time frame: Baseline and Month 12

Change in Patient Global Assessment

Change from baseline OA disease activity as assessed by Patient Global Assessment for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 24.

Time frame: Baseline and Month 24

Change in Patient Global Assessment

Change from baseline OA disease activity as assessed by Patient Global Assessment for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 36.

Time frame: Baseline and Month 36

Change in Patient Global Assessment

Change from baseline OA disease activity as assessed by Patient Global Assessment for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 48.

Time frame: Baseline and Month 48

Change in Patient Global Assessment

Change from baseline OA disease activity as assessed by Patient Global Assessment for both the (previously injected) SM04690 treatment arms and the (previously injected) placebo treatment arm at Month 60.

Time frame: Baseline and Month 60