3-year, Open-Label Study Evaluating Safety, Tolerability, and Efficacy of Lorecivivint in Knee Osteoarthritis

A 3-Year, Multicenter, Open-Label Study Evaluating the Safety, Tolerability, and Efficacy of Intra-articular Lorecivivint in Subjects With Osteoarthritis of the Knee in a Real-World Setting (STRIDES-EXTRA)

This study is designed as a 3-year, multicenter, open-label study evaluating the safety, tolerability, and efficacy of intra-articular (IA) Lorecivivint (LOR) in subjects with osteoarthritis of the knee in a real-world setting.

Study Overview

• Status: Terminated
• Conditions: Osteoarthritis of the Knee
• Intervention / Treatment: Drug: Lorecivivint

Detailed Description

At Day 1, after a screening period of up to 14 days, subjects will receive an IA injection of 0.07 mg LOR into one or both knees, followed by a 36-month evaluation period.

Clinic visits will be scheduled at Day 1, and Months 3, 12, 24, and 36 [End of study (EOS)] or Early Termination (ET).

All Patient Reported Outcome (PRO) measurements, including Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and Pain Numeric Rating Scale (NRS), as well as safety evaluations will be conducted at each clinic visit. An additional phone follow-up visit for safety will occur 4 weeks after the injection on Day 1.

Study was terminated by Sponsor based on a business decision not due to safety. The study report was finalized without any statistical analysis.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Research Site
  • Florida
    • Winter Park, Florida, United States, 32789
      • Research Site
  • Illinois
    • Oak Brook, Illinois, United States, 60523
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75231
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males and females between 40 and 80 years of age, inclusive, in general good health apart from their knee OA
2. Femorotibial OA by standard American College of Rheumatology (ACR) criteria; knee OA is not to be secondary to any rheumatologic conditions (e.g., rheumatoid arthritis).
3. Pain compatible with knee OA for at least 26 weeks prior to the Screening Visit
4. Negative drug test for amphetamine, buprenorphine, cocaine, methadone, opiates, phencyclidine (PCP), propoxyphene, barbiturates, and benzodiazepine, unless any of these drugs are prescribed by a physician to treat a specific condition
5. Full understanding of the requirements of the study and willingness to comply with all study visits and assessments
6. Subjects must have read and understood the informed consent form (ICF), and must have signed and dated it prior to any study-related procedure being performed

Exclusion Criteria:

1. 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 Screening and Day 1
2. Women who are not post-menopausal or permanently surgically sterile who are sexually active, and who are not willing to use birth control during the study period
3. Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to Day 1
4. Intra-articular (IA) injection into either knee with a therapeutic aim including, but not limited to, hyaluronic acid, platelet-rich plasma (PRP), and stem cell therapies within 26 weeks prior to Day 1 or IA glucocorticoids within 12 weeks prior to Day 1
5. 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
6. Any comorbid condition that could affect study endpoint assessments of the knee, including, but not limited to, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, gout or pseudogout, and fibromyalgia
7. Any contraindications for an IA injection in the knee(s) to be injected at Day 1 in the opinion of the Investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.07 mg Lorecivivint; One intra-articular injection of 0.07 mg Lorecivivint in 2 ml vehicle in one or both knees as clinically indicated. Bilateral injection of 0.07 mg LOR are allowed. Lorecivivint: Healthcare professional-administered intra-articular injection	Drug: Lorecivivint; Healthcare professional-administered intra-articular (IA) injection into one or both knees as clinically indicated. Bilateral injections of 0.07 mg of LOR are allowed. IA injection performed on Day 1. Additional IA injections of LOR to same knee (with at least a 6 month separation) between Day 1 and Month 33.; Other Names: SM04690

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Pain Numeric Rating Scale (NRS) Score for the Left Knee	Change from baseline in pain numeric rating scale (NRS) score for the left knee. 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. Change was calculated as three-month visit minus baseline; a negative value indicates improvement while a positive value indicates worsening.	Three Months after Day 1 Injection
Change From Baseline in Pain Numeric Rating Scale (NRS) Score for the Right Knee	Change from baseline in pain numeric rating scale (NRS) score for the right knee. 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. Change was calculated as three-month visit minus baseline; a negative value indicates improvement while a positive value indicates worsening.	Three Months after Day 1 Injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscore (WOMAC Function) in Left Knee	Change from baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index NRS3.1 physical function subscore (WOMAC Function) in left knee. The WOMAC is a widely-used, proprietary outcome measurement tool used to evaluate the condition of subjects with OA of the knee and hip, including pain, stiffness, and physical functioning of a target joint. 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 (raw) and will be scaled 0 to 100 for reporting. Change was calculated as three-month visit minus baseline; a negative value indicates improvement while a positive value indicates worsening.	Three Months after Day 1 Injection
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscore (WOMAC Function) in Right Knee	Change from baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index NRS3.1 physical function subscore (WOMAC Function) in right knee. The WOMAC is a widely-used, proprietary outcome measurement tool used to evaluate the condition of subjects with OA of the knee and hip, including pain, stiffness, and physical functioning of a target joint. 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 (raw) and will be scaled 0 to 100 for reporting. Change was calculated as three-month visit minus baseline; a negative value indicates improvement while a positive value indicates worsening.	Three Months after Day 1 Injection
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain) in Left Knee	Change from baseline OA pain in the target knee as assessed by Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index NRS3.1 pain subscore (WOMAC Pain) in left knee. The WOMAC is a widely-used, proprietary outcome measurement tool used to evaluate the condition of subjects with OA of the knee and hip, including pain, stiffness, and physical functioning of a target joint. 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 to 50 (raw) and will be scaled 0 to 100 for reporting. Change was calculated as three-month visit minus baseline; a negative value indicates improvement while a positive value indicates worsening.	Three Months after Day 1 Injection
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain) in Right Knee	Change from baseline OA pain in the target knee as assessed by Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index NRS3.1 pain subscore (WOMAC Pain) in right knee. The WOMAC is a widely-used, proprietary outcome measurement tool used to evaluate the condition of subjects with OA of the knee and hip, including pain, stiffness, and physical functioning of a target joint. 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 to 50 (raw) and will be scaled 0 to 100 for reporting. Change was calculated as three-month visit minus baseline; a negative value indicates improvement while a positive value indicates worsening.	Three Months after Day 1 Injection

Collaborators and Investigators

• Sponsor: Biosplice Therapeutics, Inc.
• Investigators: Study Director: Yusuf Yazici, MD, Biosplice Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2021
• Primary Completion (Actual): December 13, 2021
• Study Completion (Actual): December 13, 2021

Study Registration Dates

• First Submitted: June 4, 2021
• First Submitted That Met QC Criteria: June 11, 2021
• First Posted (Actual): June 18, 2021

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: osteoarthritis; Samumed; SM04690; Wnt pathway inhibitor; Biosplice Therapeutics, Inc.; Lorecivivint; 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-17

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