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

• Sponsor: Biosplice Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02951026
• Collaborator: (none)
• Enrollment: 703
• Locations: 62
• Actual Duration (Months): 37.4
• Patients Per Site: 11.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis	Other: Not applicable (no therapy is administered as part of this study)

Study Design

• Study Type: Observational
• Actual Enrollment: 703 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: 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
• Actual Study Start Date: Sep 19, 2016
• Actual Primary Completion Date: Oct 31, 2019
• Actual Study Completion Date: Oct 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
0.03mg SM04690 (previously injected) 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); 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.
0.07mg SM04690 (previously injected) 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); 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.
0.23mg SM04690 (previously injected) 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); 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.
Placebo (previously injected) 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); 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.

Outcome Measures

Primary Outcome Measures

1. Incidence rate of serious adverse events (SAEs) [Month 60]

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

Secondary Outcome Measures

1. Adverse events (AEs) of interest [Month 6]

   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).

2. AEs of interest [Month 12]

   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.

3. AEs of interest [Month 24]

   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.

4. AEs of interest [Month 36]

   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.

5. AEs of interest [Month 48]

   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.

6. AEs of interest [Month 60]

   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.

7. Incidence and incidence rate of total knee replacement (TKR) [Month 60]

   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.

8. Change in joint space width (JSW) [Baseline and Month 6]

   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.

9. Change in joint space width (JSW) [Baseline and Month 12]

   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.

10. Change in joint space width (JSW) [Baseline and Month 24]

    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.

11. Change in joint space width (JSW) [Baseline and Month 36]

    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.

12. Change in joint space width (JSW) [Baseline and Month 48]

    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.

13. Change in joint space width (JSW) [Baseline and Month 60]

    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.

14. Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score [Baseline and Month 6]

    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.

15. Change in WOMAC total score [Baseline and Month 12]

    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.

16. Change in WOMAC total score [Baseline and Month 24]

    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.

17. Change in WOMAC total score [Baseline and Month 36]

    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.

18. Change in WOMAC total score [Baseline and Month 48]

    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.

19. Change in WOMAC total score [Baseline and Month 60]

    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.

20. Change in WOMAC pain subscore [Baseline and Month 6]

    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.

21. Change in WOMAC pain subscore [Baseline and Month 12]

    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.

22. Change in WOMAC pain subscore [Baseline and Month 24]

    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.

23. Change in WOMAC pain subscore [Baseline and Month 36]

    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.

24. Change in WOMAC pain subscore [Baseline and Month 48]

    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.

25. Change in WOMAC pain subscore [Baseline and Month 60]

    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.

26. Change in WOMAC function subscore [Baseline and Month 6]

    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.

27. Change in WOMAC function subscore [Baseline and Month 12]

    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.

28. Change in WOMAC function subscore [Baseline and Month 24]

    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.

29. Change in WOMAC function subscore [Baseline and Month 36]

    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.

30. Change in WOMAC function subscore [Baseline and Month 48]

    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.

31. Change in WOMAC function subscore [Baseline and Month 60]

    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.

32. Change in Physician Global Assessment [Baseline and Month 6]

    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.

33. Change in Physician Global Assessment [Baseline and Month 12]

    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.

34. Change in Physician Global Assessment [Baseline and Month 24]

    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.

35. Change in Physician Global Assessment [Baseline and Month 36]

    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.

36. Change in Physician Global Assessment [Baseline and Month 48]

    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.

37. Change in Physician Global Assessment [Baseline and Month 60]

    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.

38. Change in Patient Global Assessment [Baseline and Month 6]

    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.

39. Change in Patient Global Assessment [Baseline and Month 12]

    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.

40. Change in Patient Global Assessment [Baseline and Month 24]

    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.

41. Change in Patient Global Assessment [Baseline and Month 36]

    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.

42. Change in Patient Global Assessment [Baseline and Month 48]

    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.

43. Change in Patient Global Assessment [Baseline and Month 60]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States
2	Research Site	Oro Valley	Arizona	United States
3	Research Site	Phoenix	Arizona	United States
4	Research Site	Tucson	Arizona	United States
5	Research Site	Canoga Park	California	United States
6	Research Site	Carmichael	California	United States
7	Research Site	Cerritos	California	United States
8	Research Site	El Cajon	California	United States
9	Research Site	Gold River	California	United States
10	Research Site	La Mesa	California	United States
11	Research Site	Palm Springs	California	United States
12	Research Site	Rancho Mirage	California	United States
13	Research Site	Sacramento	California	United States
14	Research Site	San Diego	California	United States
15	Research Site	San Marcos	California	United States
16	Research Site	Spring Valley	California	United States
17	Research Site	Boulder	Colorado	United States
18	Research Site	Stamford	Connecticut	United States
19	Research Site	Trumbull	Connecticut	United States
20	Research Site	Waterbury	Connecticut	United States
21	Research Site	Clearwater	Florida	United States
22	Research Site	Coral Gables	Florida	United States
23	Research Site	DeLand	Florida	United States
24	Research Site	Edgewater	Florida	United States
25	Research Site	Lauderdale Lakes	Florida	United States
26	Research Site	Miami	Florida	United States
27	Research Site	Marietta	Georgia	United States
28	Research Site	Woodstock	Georgia	United States
29	Research Site	Chicago	Illinois	United States
30	Research Site	Newton	Kansas	United States
31	Research Site	Wichita	Kansas	United States
32	Research Site	Lexington	Kentucky	United States
33	Research Site	Frederick	Maryland	United States
34	Research Site	Boston	Massachusetts	United States
35	Research Site	Troy	Michigan	United States
36	Research Site	Kansas City	Missouri	United States
37	Research Site	Saint Louis	Missouri	United States
38	Research Site	Saint Peters	Missouri	United States
39	Research Site	Lincoln	Nebraska	United States
40	Research Site	Las Vegas	Nevada	United States
41	Research Site	Albuquerque	New Mexico	United States
42	Research Site	Orchard Park	New York	United States
43	Research Site	Rochester	New York	United States
44	Research Site	Charlotte	North Carolina	United States
45	Research Site	High Point	North Carolina	United States
46	Research Site	Raleigh	North Carolina	United States
47	Research Site	Salisbury	North Carolina	United States
48	Research Site	Cincinnati	Ohio	United States
49	Research Site	Cleveland	Ohio	United States
50	Research Site	Duncansville	Pennsylvania	United States
51	Research Site	Philadelphia	Pennsylvania	United States
52	Research Site	Charleston	South Carolina	United States
53	Research Site	Mount Pleasant	South Carolina	United States
54	Research Site	Rapid City	South Dakota	United States
55	Research Site	Knoxville	Tennessee	United States
56	Research Site	Austin	Texas	United States
57	Research Site	Bedford	Texas	United States
58	Research Site	Houston	Texas	United States
59	Research Site	San Angelo	Texas	United States
60	Research Site	Layton	Utah	United States
61	Research Site	Arlington	Virginia	United States
62	Research Site	Charlottesville	Virginia	United States

Sponsors and Collaborators

• Biosplice Therapeutics, Inc.

Investigators

• Study Director: Yusuf Yazici, M.D., Biosplice Therapeutics, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Biosplice Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02951026
• Other Study ID Numbers: SM04690-OA-05
• First Posted: Nov 1, 2016
• Last Update Posted: Apr 17, 2020
• Last Verified: Apr 1, 2020

• Keywords provided by Biosplice Therapeutics, Inc.: knee; osteoarthritis; intra-articular injection; SM04690
• Additional relevant MeSH terms: Osteoarthritis

Study Results

No Results Posted as of Apr 17, 2020