Patient-Reported and Radiographic Outcomes in Evaluating Lorecivivint (SM04690) for the Treatment of Knee Osteoarthritis (STRIDES-Xray)

A 56-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of a Single Injection of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects

This phase 3 study is a multicenter, randomized, double-blind, placebo-controlled study of lorecivivint injected intra-articularly (IA) into the target knee (most painful) joint of moderately to severely symptomatic osteoarthritis (OA) subjects at a single dose of 0.07 mg lorecivivint per 2 mL injection. This study will utilize radiographs and patient reported outcomes (PROs) to evaluate the safety and efficacy of lorecivivint.

Study Overview

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

Detailed Description

SM04690-OA-11 was a phase 3, 56-week multicenter, randomized, double-blind, placebo-controlled, parallel group study investigating the safety, tolerability and efficacy of LOR 0.07 mg (compared with PBO) injected into the target knee joint of moderately to severely symptomatic knee OA subjects.

Patient-reported outcomes included Pain Numeric Rating Scale (NRS) [0-10], Western Ontario and McMaster Universities Arthritis Index (WOMAC), and Patient Global Assessment (PGA) of knee osteoarthritis. Joint space as measured by a positioner-assisted posterior-anterior x-ray was the radiographic outcome.

The primary efficacy endpoint was change from baseline in target knee Pain NRS at Week 12. Secondary endpoints included change at Week 12 in WOMAC Function and PGA, as well as change in joint space at Week 52.

• Study Type: Interventional
• Enrollment (Actual): 501
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Research Site
    • Birmingham, Alabama, United States, 35216
      • Research Site
    • Birmingham, Alabama, United States, 35215
      • Research Site
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Research Site
    • Phoenix, Arizona, United States, 85037
      • Research Site
    • Tucson, Arizona, United States, 85712
      • Research Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Research Site
  • California
    • Anaheim, California, United States, 92805
      • Research Site
    • Garden Grove, California, United States, 92840
      • Research Site
    • Norco, California, United States, 92860
      • Research Site
    • Pomona, California, United States, 91767
      • Research Site
    • San Diego, California, United States, 92103
      • Research Site
    • San Marcos, California, United States, 92078
      • Research Site
    • Spring Valley, California, United States, 91978
      • Research Site
    • Westminster, California, United States, 92683
      • Research Site
  • Colorado
    • Boulder, Colorado, United States, 80301
      • Research Site
    • Colorado Springs, Colorado, United States, 80918
      • Research Site
    • Denver, Colorado, United States, 80209
      • Research Site
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Research Site
  • Florida
    • Clearwater, Florida, United States, 33761
      • Research Site
    • Coral Gables, Florida, United States, 33134
      • Research Site
    • Hialeah, Florida, United States, 33016
      • Research Site
    • Miami, Florida, United States, 33143
      • Research Site
    • Miami Lakes, Florida, United States, 33014
      • Research Site
    • Orlando, Florida, United States, 32806
      • Research Site
    • Oviedo, Florida, United States, 32765
      • Research Site
    • Port Orange, Florida, United States, 32127
      • Research Site
    • Sunrise, Florida, United States, 33351
      • 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 #1
    • Winter Park, Florida, United States, 32789
      • Research Site #2
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Research Site
    • Newnan, Georgia, United States, 30265
      • Research Site
    • Stockbridge, Georgia, United States, 30281
      • Research Site
    • Woodstock, Georgia, United States, 30189
      • Research Site
  • Idaho
    • Boise, Idaho, United States, 83713
      • Research Site
    • Meridian, Idaho, United States, 83642
      • Research Site
  • Illinois
    • Bloomington, Illinois, United States, 61704
      • Research Site
    • Gurnee, Illinois, United States, 60031
      • Research Site
    • Oak Brook, Illinois, United States, 60523
      • Research Site
    • Rockford, Illinois, United States, 61114
      • Research Site
  • Indiana
    • Anderson, Indiana, United States, 46011
      • Research Site
    • Evansville, Indiana, United States, 47714
      • Research Site
    • Valparaiso, Indiana, United States, 46383
      • Research Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Research Site
    • Wichita, Kansas, United States, 67205
      • Research Site
  • Louisiana
    • Monroe, Louisiana, United States, 71203
      • Research Site
    • New Orleans, Louisiana, United States, 70124
      • Research Site
  • Maryland
    • Wheaton, Maryland, United States, 20902
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • 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
    • La Vista, Nebraska, United States, 68128
      • Research Site
    • Lincoln, Nebraska, United States, 68516
      • Research Site
    • Omaha, Nebraska, United States, 68114
      • Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108
      • Research Site
  • New York
    • Great Neck, New York, United States, 11021
      • Research Site
    • Hartsdale, New York, United States, 10530
      • Research Site
    • New York, New York, United States, 10016
      • Research Site
    • New York, New York, United States, 10021
      • Research Site 1
    • New York, New York, United States, 10021
      • Research Site 2
    • Rochester, New York, United States, 14609
      • Research Site
    • Williamsville, New York, United States, 14221
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • Research Site
    • Leland, North Carolina, United States, 28451
      • Research Site
    • Salisbury, North Carolina, United States, 28144
      • Research Site
    • Winston-Salem, North Carolina, United States, 27103
      • Research Site
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Research Site
    • Cincinnati, Ohio, United States, 45219
      • Research Site
    • Cincinnati, Ohio, United States, 45224
      • Research Site
    • Columbus, Ohio, United States, 43235
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Research Site
    • Oklahoma City, Oklahoma, United States, 73103
      • Research Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Research Site
  • South Carolina
    • Fort Mill, South Carolina, United States, 29707
      • Research Site
    • Greenville, South Carolina, United States, 29607
      • Research Site
    • Greer, South Carolina, United States, 29651
      • Research Site
    • Mt. Pleasant, South Carolina, United States, 29464
      • Research Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Research Site
  • Texas
    • Austin, Texas, United States, 78745
      • Research Site
    • Bedford, Texas, United States, 76021
      • Research Site
    • Carrollton, Texas, United States, 75007
      • Research Site
    • Dallas, Texas, United States, 75231
      • Research Site
    • Edinburg, Texas, United States, 78539
      • Research Site
    • Houston, Texas, United States, 77029
      • Research Site
    • Houston, Texas, United States, 77055
      • Research Site
    • Plano, Texas, United States, 75075
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site
    • San Antonio, Texas, United States, 78215
      • Research Site
    • San Antonio, Texas, United States, 78258
      • Research Site
  • Utah
    • Draper, Utah, United States, 84020
      • Research Site
    • Murray, Utah, United States, 84123
      • Research Site
    • Salt Lake City, Utah, United States, 84107
      • Research Site
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Research Site
    • Richmond, Virginia, United States, 23219
      • 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. Ambulatory (single assistive devices such as canes allowed if needed less than 50% of the time, subjects requiring a walker are excluded)
3. Diagnosis of femorotibial OA in the target knee by standard American College of Rheumatology (ACR) criteria at the Screening Visit (clinical AND radiographic criteria); OA of the knee is not to be secondary to any rheumatologic conditions (e.g., rheumatoid arthritis)
4. mJSW by radiograph between 1.5 and 4 mm, inclusive, in the target knee within 12 weeks of the Screening Visit as assessed by independent central readers
5. Radiographic disease Stage 2 or 3 in the target knee within 12 weeks of the Screening Visit according to the Kellgren-Lawrence (KL) grading of knee OA as assessed by independent central readers
6. Pain compatible with OA of the knee(s) for at least 26 weeks prior to the Screening Visit
7. Primary source of pain throughout the body is due to OA in the target knee
8. Body mass index (BMI) ≤ 40 kg/m2 at the Screening Visit
9. Widespread Pain Index (WPI) score of ≤ 4 and a Symptom Severity Question 2 (SSQ2) score of ≤ 2 at the Screening Visit and Day 1
10. Pain NRS scores recorded for the target knee on at least 4 out of the 7 days immediately preceding Day 1
11. Pain NRS scores recorded for the nontarget knee on at least 4 out of the 7 days immediately preceding Day 1
12. Daily OA knee pain diary average NRS intensity score ≥ 4 and ≤ 8 in the target knee on the 11-point (0-10) NRS scale for the 7 days immediately preceding Day 1
13. Daily OA knee pain diary average NRS intensity score < 4 in the nontarget knee on the 11-point (0-10) NRS scale for the 7 days immediately preceding Day 1
14. WOMAC Pain of 20-40 (out of 50) for the target knee at baseline regardless of if the subject is on symptomatic oral treatment (baseline questionnaire completed during the screening period prior to randomization)
15. WOMAC Function of 68-136 (out of 170) for the target knee at baseline regardless of if the subject is on symptomatic oral treatment (baseline questionnaire completed during the screening period prior to randomization)
16. Willingness to use an electronic diary daily in the evening for the screening period and 56-week study duration
17. Negative drug test for amphetamine, buprenorphine, cocaine, methadone, opiates, phencyclidine (PCP), propoxyphene, barbiturates, benzodiazepine, methaqualone, and tricyclic antidepressants, unless any of these drugs are allowed per protocol and prescribed by a physician to treat a specific condition
18. Subjects with depression or anxiety must be clinically stable for at least 12 weeks prior to the Screening Visit and, if on treatment for depression or anxiety, be on at least 12 weeks of stable therapy
19. Full understanding of the requirements of the study and willingness to comply with all study visits and assessments
20. 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 woman, 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 the Screening Visit or 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. Men who are sexually active and of reproductive potential, who have partners who are capable of becoming pregnant, and who are not willing to use birth control during the study period
4. Significant malalignment of anatomical axis (medial angle formed by the femur and tibia) of the target knee (varus > 10°, valgus > 10°) by radiograph within 12 weeks of the Screening Visit as assessed by independent central readers
5. Partial or complete joint replacement in either knee
6. Currently requires use of a lower extremity prosthesis, and/or a structural knee brace (i.e., a knee brace that contains hardware)
7. Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to Day 1
8. Intra-articular (IA) injection into the target 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
9. Effusion of the target knee clinically requiring aspiration within 12 weeks prior to Day 1
10. Use of electrotherapy, acupuncture, physical therapy, therapeutic ultrasound, and/or chiropractic treatments for knee OA within 4 weeks prior to Day 1
11. Any bone fracture(s) within 26 weeks prior to the Screening Visit
12. Previous treatment with SM04690
13. Subjects who have previously failed screening on this protocol and fail to meet rescreening criteria
14. Participation in a clinical research trial that included the receipt of an investigational product (IP) or any experimental therapeutic procedure within 26 weeks prior to the Screening Visit, or planned participation in any such trial
15. Treatment with systemic (oral, intramuscular, or intravenous) glucocorticoids ≥10 mg prednisone or the equivalent per day within 4 weeks prior to Day 1, or subjects on <10 mg prednisone or the equivalent per day who have not maintained a stable regimen for at least 2 weeks prior to Day 1 in the opinion of the Investigator
16. Use of centrally acting analgesics within 12 weeks prior to Day 1
17. Use of anticonvulsants within 12 weeks prior to Day 1
18. Subjects requiring the use of opioids > 1x per week within 12 weeks prior to Day 1
19. Topical local anesthetic agents (gels, creams, or patches such as the Lidoderm patch) used for the treatment of knee OA within 7 days of Day 1
20. Planned surgery scheduled during the study period, not including non-surgical invasive procedures conducted for a diagnostic or therapeutic purpose scheduled during the study period
21. History of malignancy within the last 5 years, not including subjects with prior history of adequately treated in situ cervical cancer or basal or squamous cell skin cancer
22. Clinically significant abnormal screening hematology values, blood chemistry values, or urinalysis values as determined by the Investigator
23. 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
24. Other conditions that, in the opinion of the Investigator, could affect study endpoint assessments of either knee, including, but not limited to, peripheral neuropathy (e.g., diabetic neuropathy), symptomatic hip osteoarthritis, symptomatic degenerative disc disease, and patellofemoral syndrome
25. Comorbid conditions that could affect study endpoint assessments of the target knee, including, but not limited to, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, gout or pseudogout, and fibromyalgia
26. History of mania, bipolar disorder, psychotic disorder, schizophrenia, or schizoaffective disorder
27. Any known active infections, including urinary tract infection, upper respiratory tract infection, sinusitis, suspicion of IA infection, hepatitis B or hepatitis C infection, and/or infections that may compromise the immune system such as human immunodeficiency virus (HIV) at Day 1
28. Any chronic condition that has not been well controlled or subjects with a chronic condition who have not maintained a stable therapeutic regimen of a prescription therapy in the opinion of the Investigator.
29. Hemoglobin A1c (HbA1c) >9 at the Screening Visit
30. If using NSAIDs and/or acetaminophen, subjects who have not maintained a stable regimen in the opinion of the Investigator for at least 4 weeks prior to Day 1
31. Any contraindications for an IA injection in the target knee in the opinion of the Investigator
32. Subjects who have a current or pending disability claim, workers' compensation, or litigation(s) that may compromise response to treatment
33. Subjects who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at any investigative site, or are directly affiliated with the study at any investigative site
34. 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, or who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of said employees responsible for the conduct of the study

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: 0.07 mg lorecivivint; One intra-articular injection of 0.07 mg lorecivivint in 2 ml vehicle	Drug: Lorecivivint; Healthcare professional-administered intra-articular injection; performed on Day 1; Other Names: SM04690
Placebo Comparator: Vehicle; One intra-articular injection of 0 mg lorecivivint in 2 ml vehicle	Drug: Placebo; Healthcare professional-administered intra-articular injection; performed on Day 1; Other Names: Vehicle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in OA Pain in the Target Knee (Pain NRS)	Evaluate change from 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.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in OA Pain in the Target Knee (Pain NRS)	Evaluate change from 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.	Baseline and Week 24
Change From Baseline in OA Pain in the Target Knee (Pain NRS)	Evaluate change from 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.	Baseline and Week 52
Change From Baseline in OA Function in the Target Knee (WOMAC Function)	Evaluate change from baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function subscore (WOMAC Function). 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 (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on an 11-point numeric rating scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Function raw subscore ranges from 0 to 170, and is scaled 0 (highest overall function) to 100 (lowest overall function) for analysis and reporting.	Baseline and Week 12
Change From Baseline in OA Function in the Target Knee (WOMAC Function)	Evaluate change from baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function subscore (WOMAC Function). 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 (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on an 11-point numeric rating scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Function raw subscore ranges from 0 to 170, and is scaled 0 (highest overall function) to 100 (lowest overall function) for analysis and reporting.	Baseline and Week 24
Change From Baseline in OA Function in the Target Knee (WOMAC Function)	Evaluate change from baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function subscore (WOMAC Function). 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 (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on an 11-point numeric rating scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Function raw subscore ranges from 0 to 170, and is scaled 0 (highest overall function) to 100 (lowest overall function) for analysis and reporting.	Baseline and Week 52
Change From Baseline in OA Disease Activity (Patient Global Assessment)	Evaluate change from baseline OA disease activity as assessed by Patient Global Assessment. The Patient Global Assessment is an 11-point [0-10] Numeric Rating Scale [NRS] on which the subjects will rate how they feel their target knee OA is doing, considering all the ways in which their target knee OA may affect them. The NRS is anchored by descriptors at each end ("Very Good" on the left and "Very Bad" on the right). For analysis, Patient Global Assessment scores were scaled to [0-100], where 0 represents "Very Good" and 100 represents "Very Bad".	Baseline and Week 12
Change From Baseline in OA Disease Activity (Patient Global Assessment)	Evaluate change from baseline OA disease activity as assessed by Patient Global Assessment. The Patient Global Assessment is an 11-point [0-10] Numeric Rating Scale [NRS] on which the subjects will rate how they feel their target knee OA is doing, considering all the ways in which their target knee OA may affect them. The NRS is anchored by descriptors at each end ("Very Good" on the left and "Very Bad" on the right). For analysis, Patient Global Assessment scores were scaled to [0-100], where 0 represents "Very Good" and 100 represents "Very Bad".	Baseline and Week 24
Change From Baseline in OA Disease Activity (Patient Global Assessment)	Evaluate change from baseline OA disease activity as assessed by Patient Global Assessment. The Patient Global Assessment is an 11-point [0-10] Numeric Rating Scale [NRS] on which the subjects will rate how they feel their target knee OA is doing, considering all the ways in which their target knee OA may affect them. The NRS is anchored by descriptors at each end ("Very Good" on the left and "Very Bad" on the right). For analysis, Patient Global Assessment scores were scaled to [0-100], where 0 represents "Very Good" and 100 represents "Very Bad".	Baseline and Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Medial Joint Space Width (mJSW) in the Target Knee	Evaluate change from baseline in mJSW as documented by radiograph of the target knee	Baseline and Week 52

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Tambiah J, Kennedy S, Swearingen C, McAlindon T, Yazici Y. Impact of structural severity on outcomes in knee osteoarthritis: an analysis of data from phase 2 and phase 3 lorecivivint clinical trials. Rheumatology (Oxford). 2025 May 1;64(5):2583-2590. doi: 10.1093/rheumatology/keae610.

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2019
• Primary Completion (Actual): August 20, 2021
• Study Completion (Actual): August 20, 2021

Study Registration Dates

• First Submitted: April 23, 2019
• First Submitted That Met QC Criteria: April 23, 2019
• First Posted (Actual): April 26, 2019

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: osteoarthritis; Samumed; SM04690; Wnt pathway inhibitor; lorecivivint
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee; Anti-Inflammatory Agents; lorecivivint
• Other Study ID Numbers: SM04690-OA-11

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