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

Study OA-07 was a randomized, double-blind, placebo-controlled, Phase 3, multicenter, 2-year clinical trial that enrolled subjects from the recently completed Study OA-11 (NCT03928184).

The first 48 weeks of OA-07 the trial was placebo-controlled with subjects receiving the same randomized treatment received in OA-11. Investigators, research staff and subjects remained blinded to treatment allocation.

At Week 48, all subjects were administered LOR in the open-label portion of the trial.

Study Overview

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

Detailed Description

At Visit 1E (on Day 1), upon completion of initial study procedures (e.g., informed consent, eligibility requirements, clinical evaluations including pregnancy testing [as applicable], baseline patient-reported outcome [PRO] assessments and safety data collection), subjects received a blinded IA injection of either LOR or PBO (as originally randomized in the parent [OA-11] study) into their target knee.

At Visit 3E (Week 48), upon completion of scheduled clinical, medical, safety and Patient-reported outcome (PRO) assessments, all subjects received an open-label injection of IA LOR into their target knee, such that previously PBO-treated subjects were effectively crossed over to the LOR treatment cohort.

Subjects were given the option to either receive a final injection of IA LOR into their target knee and complete both Visit 6E (Week 100) assessments and End-of-Study Visit assessments, or receive no injection and complete End-of-Study Visit assessments only. Subjects who had completed Visit 6E prior to the announcement of study closure were instructed to return to the clinic for End-of-Study Visit assessments.

Study OA-07's initial study design was to assess the safety and efficacy of additional treatment with LOR compared to PBO over one year and conclude at Visit 3E. The study was amended to become an open-label study at the Visit 3E that included an End-of-Study visit but without a specified time. The study was intended and described in the protocol to be run until such time as the Sponsor chose to close it. Study OA-07 was administratively closed at Visit 6E (Week 100), with no safety concerns, one year into the open-label study. For these reasons, Study OA-07 is considered a completed 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
    • St 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
    • Mt. 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 Study SM04690-OA-11 (NCT03928184)
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: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lorecivivint; 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
Placebo Comparator: Placebo; 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
Change From OA-11-study Baseline Medial Joint Space Width (mJSW) in the Target Knee	Change from OA-11-study baseline in mJSW measured in millimeters as documented by radiograph (X-ray) of the target knee. JSW measurements were provided by a blinded, central imaging vendor using landmark-based, computer-assisted proprietary methodology.	OA-11-study baseline; Visit 3E (Week 48)
Change From OA-07-study Baseline OA Pain in the Target Knee	Change from OA-07-study baseline OA pain the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain). 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 Pain subscore ranges from 0 [no pain] to 100 [pain as bad as it can be].	OA-07-study baseline; Visit 2E (Week 24)
Change From OA-07-study Baseline OA Function in the Target Knee	Change from OA-07-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 [highest functional status] to 100 [most impaired functional status].	OA-07-study baseline; Visit 2E (Week 24)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From OA-07-study Baseline OA Pain in the Target Knee	Change from OA-07-study baseline OA pain the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain). 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 Pain subscore ranges from 0 [no pain] to 100 [pain as bad as it can be].	OA-07-study baseline; Visit 3E (Week 48)
Change From OA-07-study Baseline OA Function in the Target Knee	Change from OA-07-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 [highest functional status] to 100 [most impaired functional status].	OA-07-study baseline; Visit 3E (Week 48)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From OA-11-study Baseline Medial Joint Space Width (mJSW) in the Target Knee	Change from OA-11-study baseline in mJSW measured in millimeters as documented by radiograph (X-ray) of the target knee. JSW measurements were provided by a blinded, central imaging vendor using landmark-based, computer-assisted proprietary methodology.	OA-11-study baseline; Visit 6E (Week 100)

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 (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: osteoarthritis; Samumed; SM04690; Wnt pathway inhibitor; lorecivivint; Biosplice Therapeutics, Inc.; DYRK inhibitor; CLK inhibitor
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; 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