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

Study Overview
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Brief Summary
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This long-term extension study is designed to monitor the long-term safety, tolerability, and efficacy of treatment of SM04690 or placebo previously injected in the target knee joints of subjects with moderately to severely symptomatic osteoarthritis (OA) from a Samumed-sponsored SM04690-OA phase 2 or phase 3 study. No additional SM04690 or placebo therapy will be administered in this study.

Official Title
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A Phase 3, Multicenter, Observational Long-term 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

Conditions
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Osteoarthritis

Intervention / Treatment
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* Other: Not applicable (no therapy is administered as part of this study)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completion of scheduled end-of-study visit of Samumed-sponsored SM04690-OA phase 2 or phase 3 studies Full understanding of the requirements of the study and willingness to comply with all study visits and assessments Subjects must have read and understood the informed consent form, and must have signed it prior to any study-related procedure being performed Exclusion Criteria: Unable to undergo the radiograph procedures detailed within the protocol Partial or complete joint replacement in the target knee Subjects who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at the investigative site, or are directly affiliated with the study at the investigative site Subjects employed by Samumed, LLC, or any of its affiliates or development partners (that is, an employee, temporary contract worker, or designee) responsible for the conduct of the study

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 0.03mg SM04690 (previously injected)<br>Subjects in this group received a single intra-articular injection of 0.03mg SM04690 into the target knee during the parent study prior to enrolling in this observational study. | Other: Not applicable (no therapy is administered as part of this study)<br>* No experimental therapy or placebo is being administered in this study. All subjects in this observational study received a single intra-articular injection of SM04690 or placebo in a prior parent study.<br>|
| 0.07mg SM04690 (previously injected)<br>Subjects in this group received a single intra-articular injection of 0.07mg SM04690 into the target knee during the parent study prior to enrolling in this observational study. | Other: Not applicable (no therapy is administered as part of this study)<br>* No experimental therapy or placebo is being administered in this study. All subjects in this observational study received a single intra-articular injection of SM04690 or placebo in a prior parent study.<br>|
| 0.23mg SM04690 (previously injected)<br>Subjects in this group received a single intra-articular injection of 0.23mg SM04690 into the target knee during the parent study prior to enrolling in this observational study. | Other: Not applicable (no therapy is administered as part of this study)<br>* No experimental therapy or placebo is being administered in this study. All subjects in this observational study received a single intra-articular injection of SM04690 or placebo in a prior parent study.<br>|
| Placebo (previously injected)<br>Subjects in this group received a single intra-articular injection of placebo into the target knee during the parent study prior to enrolling in this observational study. | Other: Not applicable (no therapy is administered as part of this study)<br>* No experimental therapy or placebo is being administered in this study. All subjects in this observational study received a single intra-articular injection of SM04690 or placebo in a prior parent study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of serious adverse events (SAEs) | Compare the incidence rate of SAEs occurring in the (previously injected) SM04690 treatment arms to the (previously injected) placebo treatment arm by Month 60 | Month 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Baseline and Month 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SM04690, knee, osteoarthritis, intra-articular injection