Knee OsteoarthritisPhase 3STRIDES-XrayNCT03928184
Patient-Reported and Radiographic Outcomes in Evaluating Lorecivivint (SM04690) for the Treatment of Knee Osteoarthritis
A Phase 3 study testing Lorecivivint in people with Knee Osteoarthritis, run by Biosplice Therapeutics, Inc. at 99 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Knee Osteoarthritis
- What is being tested?
- Lorecivivint
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 501 participants
- Where
- 99 sitesUnited States
- Study dates
- 17 May 2019to 20 Aug 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females between 40 and 80 years of age, inclusive, in general good health apart from their knee OA
- Ambulatory (single assistive devices such as canes allowed if needed less than 50% of the time, subjects requiring a walker are excluded)
- 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)
- 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
- 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
- Pain compatible with OA of the knee(s) for at least 26 weeks prior to the Screening Visit
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- Primary source of pain throughout the body is due to OA in the target knee
- Body mass index (BMI) ≤ 40 kg/m2 at the Screening Visit
- Widespread Pain Index (WPI) score of ≤ 4 and a Symptom Severity Question 2 (SSQ2) score of ≤ 2 at the Screening Visit and Day 1
- Pain NRS scores recorded for the target knee on at least 4 out of the 7 days immediately preceding Day 1
- Pain NRS scores recorded for the nontarget knee on at least 4 out of the 7 days immediately preceding Day 1
- 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
- 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
- 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)
- 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)
- Willingness to use an electronic diary daily in the evening for the screening period and 56-week study duration
- 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
- 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
- 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 (ICF), and must have signed and dated it prior to any study-related procedure being performed
Who cannot join
- 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
- 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
- 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
- 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
- Partial or complete joint replacement in either knee
- Currently requires use of a lower extremity prosthesis, and/or a structural knee brace (i.e., a knee brace that contains hardware)
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- Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to Day 1
- 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
- Effusion of the target knee clinically requiring aspiration within 12 weeks prior to Day 1
- Use of electrotherapy, acupuncture, physical therapy, therapeutic ultrasound, and/or chiropractic treatments for knee OA within 4 weeks prior to Day 1
- Any bone fracture(s) within 26 weeks prior to the Screening Visit
- Previous treatment with SM04690
- Subjects who have previously failed screening on this protocol and fail to meet rescreening criteria
- 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
- 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
- Use of centrally acting analgesics within 12 weeks prior to Day 1
- Use of anticonvulsants within 12 weeks prior to Day 1
- Subjects requiring the use of opioids > 1x per week within 12 weeks prior to Day 1
- 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
- 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
- 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
- Clinically significant abnormal screening hematology values, blood chemistry values, or urinalysis values as determined by the Investigator
- 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
- 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
- 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
- History of mania, bipolar disorder, psychotic disorder, schizophrenia, or schizoaffective disorder
- 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
- 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.
- Hemoglobin A1c (HbA1c) >9 at the Screening Visit
- 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
- Any contraindications for an IA injection in the target knee in the opinion of the Investigator
- Subjects who have a current or pending disability claim, workers' compensation, or litigation(s) that may compromise response to treatment
- 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
- 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
Trial locations and contacts
99 sites in 1 country.
99 sites in 1 country
United States99 sites
Research Site
Albuquerque, New Mexico, 87108
Research Site
Anaheim, California, 92805
Research Site
Anderson, Indiana, 46011
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Austin, Texas, 78745
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Bay City, Michigan, 48706
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Bedford, Texas, 76021
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Birmingham, Alabama, 35205
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Birmingham, Alabama, 35215
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Birmingham, Alabama, 35216
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Bloomington, Illinois, 61704
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Boise, Idaho, 83713
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Boston, Massachusetts, 02111
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Boulder, Colorado, 80301
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Carrollton, Texas, 75007
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Charlotte, North Carolina, 28209
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Charlottesville, Virginia, 22911
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Cincinnati, Ohio, 45219
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Cincinnati, Ohio, 45224
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Cincinnati, Ohio, 45242
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Clearwater, Florida, 33761
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Colorado Springs, Colorado, 80918
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Columbus, Ohio, 43235
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Coral Gables, Florida, 33134
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Dallas, Texas, 75231
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Denver, Colorado, 80209
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Draper, Utah, 84020
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Duncansville, Pennsylvania, 16635
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Edinburg, Texas, 78539
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Evansville, Indiana, 47714
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Fargo, North Dakota, 58104
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Fort Mill, South Carolina, 29707
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Garden Grove, California, 92840
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Great Neck, New York, 11021
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Greenville, South Carolina, 29607
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Greer, South Carolina, 29651
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Gurnee, Illinois, 60031
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Hartsdale, New York, 10530
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Hazelwood, Missouri, 63042
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Hialeah, Florida, 33016
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Houston, Texas, 77029
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Houston, Texas, 77055
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Kansas City, Kansas, 66160
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La Vista, Nebraska, 68128
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Leland, North Carolina, 28451
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Lincoln, Nebraska, 68516
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Little Rock, Arkansas, 72205
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Marietta, Georgia, 30060
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Meridian, Idaho, 83642
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Miami, Florida, 33143
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Miami Lakes, Florida, 33014
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Monroe, Louisiana, 71203
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Mt. Pleasant, South Carolina, 29464
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Murray, Utah, 84123
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New Orleans, Louisiana, 70124
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New York, New York, 10016
Research Site 1
New York, New York, 10021
Research Site 2
New York, New York, 10021
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Newnan, Georgia, 30265
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Norco, California, 92860
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Oak Brook, Illinois, 60523
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Oklahoma City, Oklahoma, 73103
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Oklahoma City, Oklahoma, 73112
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Omaha, Nebraska, 68114
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Orlando, Florida, 32806
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Oviedo, Florida, 32765
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Peoria, Arizona, 85381
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Phoenix, Arizona, 85037
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Plano, Texas, 75075
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Pomona, California, 91767
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Port Orange, Florida, 32127
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Rapid City, South Dakota, 57702
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Richmond, Virginia, 23219
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Rochester, New York, 14609
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Rockford, Illinois, 61114
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Salisbury, North Carolina, 28144
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Salt Lake City, Utah, 84107
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San Antonio, Texas, 78215
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San Antonio, Texas, 78229
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San Antonio, Texas, 78258
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San Diego, California, 92103
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San Marcos, California, 92078
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Spring Valley, California, 91978
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St Louis, Missouri, 63141
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Stockbridge, Georgia, 30281
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Sunrise, Florida, 33351
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Troy, Michigan, 48085
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Tucson, Arizona, 85712
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Valparaiso, Indiana, 46383
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Waterbury, Connecticut, 06708
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West Palm Beach, Florida, 33409
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Westminster, California, 92683
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Wheaton, Maryland, 20902
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Wichita, Kansas, 67205
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Williamsville, New York, 14221
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Winston-Salem, North Carolina, 27103
Research Site
Winter Haven, Florida, 33880
Research Site #1
Winter Park, Florida, 32789
Research Site #2
Winter Park, Florida, 32789
Research Site
Woodstock, Georgia, 30189
About this study
Official title: 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.
Read the 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.
- Conditions
- Knee Osteoarthritis
- Being tested
- Lorecivivint, Placebo
- Keywords
- SM04690, Wnt pathway inhibitor, osteoarthritis, Samumed, lorecivivint
- Medical subject headings
- Osteoarthritis, Knee, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LorecivivintDrug
Also called SM04690
Healthcare professional-administered intra-articular injection; performed on Day 1
PlaceboDrug
Also called Vehicle
Healthcare professional-administered intra-articular injection; performed on Day 1
| Study group | Role | What they receive |
|---|---|---|
| 0.07 mg lorecivivint | Experimental | One intra-articular injection of 0.07 mg lorecivivint in 2 ml vehicle Receives: Drug: Lorecivivint |
| Vehicle | Placebo comparator | One intra-articular injection of 0 mg lorecivivint in 2 ml vehicle Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Week 12
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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".
Measured: 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".
Measured: 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".
Measured: Baseline and Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2019
- Study start17 May 2019
- Primary completion20 Aug 2021
- Study completion20 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Knee OsteoarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 501 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biosplice Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yusuf Yazici, M.D., Study director, Biosplice Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03928184
- Sponsor's protocol ID
- SM04690-OA-11
- Acronym
- STRIDES-Xray
- Status last verified
- Jan 2026
- First submitted
- 23 Apr 2019
- Last updated
- 13 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 39495154
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03928184
- Acronym / sponsor ID
- STRIDES-Xray / SM04690-OA-11
- Conditions
- Knee Osteoarthritis
- Keywords
- SM04690, Wnt pathway inhibitor, osteoarthritis, Samumed, lorecivivint
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 501 participants (actual)
- Lead sponsor
- Biosplice Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 17 May 2019 (actual)
- Primary completion
- 20 Aug 2021 (actual)
- Study completion
- 20 Aug 2021 (actual)
- First posted
- 26 Apr 2019 (actual)
- Results
- Posted 13 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 0.07 mg lorecivivint | Experimental | Drug: LorecivivintOne intra-articular injection of 0.07 mg lorecivivint in 2 ml vehicle |
| Vehicle | Placebo comparator | Drug: PlaceboOne intra-articular injection of 0 mg lorecivivint in 2 ml vehicle |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Males and females between 40 and 80 years of age, inclusive, in general good health apart from their knee OA
- Ambulatory (single assistive devices such as canes allowed if needed less than 50% of the time, subjects requiring a walker are excluded)
- 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)
- 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
- 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
Key exclusion criteria (34 listed)
- 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
- 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
- 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
- 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
- Partial or complete joint replacement in either knee
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LorecivivintAlso: SM04690Healthcare professional-administered intra-articular injection; performed on Day 1 | Drug | 0.07 mg lorecivivint |
| PlaceboAlso: VehicleHealthcare professional-administered intra-articular injection; performed on Day 1 | Drug | Vehicle |
Primary outcome
Change From Baseline in OA Pain in the Target Knee (Pain NRS)
Time frame: Baseline and Week 12
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.
8 secondary outcomes
Change From Baseline in OA Pain in the Target Knee (Pain NRS)
Time frame: Baseline and Week 24
Change From Baseline in OA Pain in the Target Knee (Pain NRS)
Time frame: Baseline and Week 52
Change From Baseline in OA Function in the Target Knee (WOMAC Function)
Time frame: Baseline and Week 12
Change From Baseline in OA Function in the Target Knee (WOMAC Function)
Time frame: Baseline and Week 24
Change From Baseline in OA Function in the Target Knee (WOMAC Function)
Time frame: Baseline and Week 52
Change From Baseline in OA Disease Activity (Patient Global Assessment)
Time frame: Baseline and Week 12
Change From Baseline in OA Disease Activity (Patient Global Assessment)
Time frame: Baseline and Week 24
Change From Baseline in OA Disease Activity (Patient Global Assessment)
Time frame: Baseline and Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39495154Tambiah 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yusuf Yazici, M.D. study director
Biosplice Therapeutics, Inc.
99 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lorecivivint in people with Knee Osteoarthritis, run by Biosplice Therapeutics, Inc. at 99 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 99 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in OA Pain in the Target Knee (Pain NRS) (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03928184, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2026.