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

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

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.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis
• Intervention / Treatment: Other: Not applicable (no therapy is administered as part of this study)

• Study Type: Observational
• Enrollment (Actual): 703

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Research Site
  • Arizona
    • Oro Valley, Arizona, United States
      • Research Site
    • Phoenix, Arizona, United States
      • Research Site
    • Tucson, Arizona, United States
      • Research Site
  • California
    • Canoga Park, California, United States
      • Research Site
    • Carmichael, California, United States
      • Research Site
    • Cerritos, California, United States
      • Research Site
    • El Cajon, California, United States
      • Research Site
    • Gold River, California, United States
      • Research Site
    • La Mesa, California, United States
      • Research Site
    • Palm Springs, California, United States
      • Research Site
    • Rancho Mirage, California, United States
      • Research Site
    • Sacramento, California, United States
      • Research Site
    • San Diego, California, United States
      • Research Site
    • San Marcos, California, United States
      • Research Site
    • Spring Valley, California, United States
      • Research Site
  • Colorado
    • Boulder, Colorado, United States
      • Research Site
  • Connecticut
    • Stamford, Connecticut, United States
      • Research Site
    • Trumbull, Connecticut, United States
      • Research Site
    • Waterbury, Connecticut, United States
      • Research Site
  • Florida
    • Clearwater, Florida, United States
      • Research Site
    • Coral Gables, Florida, United States
      • Research Site
    • DeLand, Florida, United States
      • Research Site
    • Edgewater, Florida, United States
      • Research Site
    • Lauderdale Lakes, Florida, United States
      • Research Site
    • Miami, Florida, United States
      • Research Site
  • Georgia
    • Marietta, Georgia, United States
      • Research Site
    • Woodstock, Georgia, United States
      • Research Site
  • Illinois
    • Chicago, Illinois, United States
      • Research Site
  • Kansas
    • Newton, Kansas, United States
      • Research Site
    • Wichita, Kansas, United States
      • Research Site
  • Kentucky
    • Lexington, Kentucky, United States
      • Research Site
  • Maryland
    • Frederick, Maryland, United States
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States
      • Research Site
  • Michigan
    • Troy, Michigan, United States
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States
      • Research Site
    • Saint Louis, Missouri, United States
      • Research Site
    • Saint Peters, Missouri, United States
      • Research Site
  • Nebraska
    • Lincoln, Nebraska, United States
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States
      • Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States
      • Research Site
  • New York
    • Orchard Park, New York, United States
      • Research Site
    • Rochester, New York, United States
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States
      • Research Site
    • High Point, North Carolina, United States
      • Research Site
    • Raleigh, North Carolina, United States
      • Research Site
    • Salisbury, North Carolina, United States
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States
      • Research Site
    • Cleveland, Ohio, United States
      • Research Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States
      • Research Site
    • Philadelphia, Pennsylvania, United States
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States
      • Research Site
    • Mount Pleasant, South Carolina, United States
      • Research Site
  • South Dakota
    • Rapid City, South Dakota, United States
      • Research Site
  • Tennessee
    • Knoxville, Tennessee, United States
      • Research Site
  • Texas
    • Austin, Texas, United States
      • Research Site
    • Bedford, Texas, United States
      • Research Site
    • Houston, Texas, United States
      • Research Site
    • San Angelo, Texas, United States
      • Research Site
  • Utah
    • Layton, Utah, United States
      • Research Site
  • Virginia
    • Arlington, Virginia, United States
      • Research Site
    • Charlottesville, Virginia, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Subjects can only participate in this study upon completion of a Samumed SM04690-OA phase 2 or phase 3 study.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Biosplice Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2016
• Primary Completion (Actual): October 31, 2019
• Study Completion (Actual): October 31, 2019

Study Registration Dates

• First Submitted: October 7, 2016
• First Submitted That Met QC Criteria: October 28, 2016
• First Posted (Estimate): November 1, 2016

Study Record Updates

• Last Update Posted (Actual): April 17, 2020
• Last Update Submitted That Met QC Criteria: April 15, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: osteoarthritis; knee; intra-articular injection; SM04690
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: SM04690-OA-05