A Long-Term Safety and Efficacy Study of Lorecivivint in Subjects With Osteoarthritis of the Knee

A Long-Term Extension Study Evaluating the Safety and Efficacy of Lorecivivint in Subjects With Osteoarthritis of the Knee

This study is designed as a long-term extension to the Phase 3 parent-study SM04690-OA-11. It aims to evaluate the safety and efficacy of long-term use of lorecivivint (LOR) in subjects with knee osteoarthritis (OA). The first 48 weeks will be single-blind and placebo-controlled while the remainder of the study will be open-label and uncontrolled. Subjects must enroll no later than 6 weeks following completion of the parent-study.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Drug: Lorecivivint; Drug: Placebo

Detailed Description

At the first visit (Day 1), all subjects will complete Patient Acceptable Symptom State (PASS) and pain Numeric Rating Scale (NRS) assessments and then receive a blinded study injection into their target knee (the same target knee injected in the parent study), with subjects receiving the same treatment (either 0.07 mg LOR or placebo) as they received in the parent study. Subjects will have clinic visits for pain and function assessments, collection of adverse events, and knee radiographs. At Week 48, all subjects, regardless of previous treatment, will receive an injection of 0.07 mg LOR into their target knee. Subjects will receive injections of 0.07 mg LOR into their target knee every 52 weeks thereafter until end of study.

• Study Type: Interventional
• Enrollment (Actual): 276
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Research Site
  • California
    • Anaheim, California, United States, 92805
      • Research Site
    • Pomona, California, United States, 91767
      • Research Site
    • San Diego, California, United States, 92103
      • Research Site
    • Thousand Oaks, California, United States, 91360
      • Research Site
  • Colorado
    • Denver, Colorado, United States, 80209
      • Research Site
  • Florida
    • Hialeah, Florida, United States, 33016
      • Research Site
    • Miami, Florida, United States, 33173
      • Research Site
    • Miami Lakes, Florida, United States, 33014
      • Research Site
    • Port Orange, Florida, United States, 32127
      • Research Site
    • West Palm Beach, Florida, United States, 33409
      • Research Site
    • Winter Haven, Florida, United States, 33880
      • Research Site
    • Winter Park, Florida, United States, 32789
      • Research Site
  • Georgia
    • Newnan, Georgia, United States, 30265
      • Research Site
    • Woodstock, Georgia, United States, 30189
      • Research Site
  • Illinois
    • Gurnee, Illinois, United States, 60031
      • Research Site
    • Oak Brook, Illinois, United States, 60523
      • Research Site
  • Indiana
    • Valparaiso, Indiana, United States, 46383
      • Research Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70124
      • Research Site
  • Michigan
    • Bay City, Michigan, United States, 48706
      • Research Site
    • Troy, Michigan, United States, 48085
      • Research Site
  • Missouri
    • Hazelwood, Missouri, United States, 63042
      • Research Site
    • Saint Louis, Missouri, United States, 63141
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Research Site
  • New York
    • Hartsdale, New York, United States, 10530
      • Research Site
    • New York, New York, United States, 10016
      • Research Site
    • Rochester, New York, United States, 14609
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • Research Site
    • Salisbury, North Carolina, United States, 28144
      • Research Site
    • Winston-Salem, North Carolina, United States, 27103
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Research Site
    • Columbus, Ohio, United States, 43235
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Research Site
  • South Carolina
    • Fort Mill, South Carolina, United States, 29707
      • Research Site
    • Mount Pleasant, South Carolina, United States, 29464
      • Research Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Research Site
  • Texas
    • Carrollton, Texas, United States, 75007
      • Research Site
    • Plano, Texas, United States, 75075
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site
  • Utah
    • Draper, Utah, United States, 84020
      • Research Site
    • Salt Lake City, Utah, United States, 84107
      • Research Site
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 41 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Completion of the Samumed study SM04690-OA-11
2. Compliance with procedures in study SM04690-OA-11, in the opinion of the Investigator
3. Fully understanding study requirements and willingness to comply with study visits and assessments
4. Understanding and signing of the informed consent form (ICF) prior to any study-related procedures

Exclusion Criteria:

1. Any condition that, in the opinion of the Investigator, constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation
2. Any contraindications for an intra-articular (IA) injection in the target knee in the opinion of the Investigator
3. Any known reason identified by the Investigator or Sponsor that the subject may not be compliant with study visits or may no longer be an appropriate candidate for the study (e.g. planned major surgery, knee replacement during the parent study, planning to move away from the research site, or initiation of a prohibited concomitant medication including, but not limited to, IA injection of glucocorticoids, hyaluronic acid derivatives, platelet-rich plasma, stem cell therapies, or other agents with therapeutic intent into the target knee)
4. Participation in a clinical research trial (other than the prior SM04690-OA-11 study) that included the receipt of an investigational product (IP) or any experimental therapeutic procedure within 12 weeks before any study injection, or planned participation in any such trial
5. Current or pending disability claim, workers' compensation, or litigation(s) that may compromise response to treatment
6. Pregnant women, breastfeeding women, and women who are not post-menopausal (defined as 12 months with no menses without an alternative medical cause) or permanently surgically sterile (includes hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) who have a positive or indeterminate pregnancy test result at Visit 1E (Day 1)
7. Women who are not post-menopausal or permanently surgically sterile who are sexually active, and who are not willing to use birth control (as outlined in the protocol) during the study period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Subjects assigned to this arm will receive one intra-articular injection of 0.07 mg lorecivivint in 2 ml vehicle (same treatment as in the parent-study) into their target knee (the same target knee injected in the parent study); performed on Day 1, at Week 48 and every 52 weeks thereafter.	Drug: Lorecivivint; Healthcare professional-administered intra-articular injections of lorecivivint.; Other Names: SM04690
Experimental: Arm 2; Subjects assigned to this arm will receive one intra-articular injection of 0 mg lorecivivint in 2 ml vehicle (same treatment as in the parent-study) into their target knee (the same target knee injected in the parent study) on Day 1, followed by one intra-articular injection of 0.07 mg lorecivivint in 2 ml vehicle at Week 48 and every 52 weeks thereafter.	Drug: Lorecivivint; Healthcare professional-administered intra-articular injections of lorecivivint.; Other Names: SM04690; Drug: Placebo; Healthcare professional-administered intra-articular injection of vehicle.; Other Names: Vehicle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Safety Outcome: Number of participants with adverse events (AEs) and serious adverse events (SAEs)	AEs that occur during the study will be recorded, and ongoing AEs at the end of the parent-study will continue to be monitored. All AEs will be evaluated for severity, seriousness and causal relationship to study medication.	Visit 1E (Day 1) through Visit 3E (Week 48)
Primary Efficacy Outcome: Change from parent-study baseline medial joint space width (mJSW) in the target knee	Change from parent-study baseline in mJSW as documented by radiograph (X-ray) of the target knee	Parent-study baseline; Visit 3E (Week 48)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from parent-study baseline OA pain in the target knee	Change from parent-study baseline OA pain in the target knee as assessed by the weekly averages of daily pain Numeric Rating Scale (NRS). The pain NRS is an 11-point scale [0-10] for subject self-reporting of average knee pain in the last 24 hours; 0 indicates no pain, and 10 represents the worst possible pain.	Parent-study baseline; Visit 2E (Week 24)
Change from parent-study baseline OA function in the target knee	Change from parent-study baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) physical functioning subscore (WOMAC Function). The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Function subscore ranges from 0 to 170.	Parent-study baseline; Visit 2E (Week 24)
Change from parent-study baseline OA pain in the target knee	Change from parent-study baseline OA pain in the target knee as assessed by the weekly averages of daily pain Numeric Rating Scale (NRS). The pain NRS is an 11-point scale [0-10] for subject self-reporting of average knee pain in the last 24 hours; 0 indicates no pain, and 10 represents the worst possible pain.	Parent-study baseline; Visit 3E (Week 48)
Change from parent-study baseline OA function in the target knee	Change from parent-study baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) physical functioning subscore (WOMAC Function). The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Function subscore ranges from 0 to 170.	Parent-study baseline; Visit 3E (Week 48)

Collaborators and Investigators

• Sponsor: Biosplice Therapeutics, Inc.
• Investigators: Study Director: Ismail Simsek, MD, Biosplice Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2020
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: August 14, 2020
• First Submitted That Met QC Criteria: August 18, 2020
• First Posted (Actual): August 20, 2020

Study Record Updates

• Last Update Posted (Estimated): December 20, 2023
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: osteoarthritis; Samumed; SM04690; Wnt pathway inhibitor; lorecivivint; Biosplice Therapeutics, Inc.
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Anti-Inflammatory Agents; Lorecivivint
• Other Study ID Numbers: SM04690-OA-07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No