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CompletedNCT05603754Updated Sep 1, 2026Results posted

Safety and Efficacy of Lorecivivint (SM04690) for the Treatment of Knee Osteoarthritis (STRIDES)

A Phase 3 interventional study of Lorecivivint and Placebo in Knee Osteoarthritis, sponsored by Biosplice Therapeutics, Inc.. Completed at 44 sites in United States. Open to participants aged 40 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-09-01.

Sponsored by Biosplice Therapeutics, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
499
Allocation
Randomized
Ages
40 Years to 80 Years
Sex
All
01

Study summary

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

Read the detailed description

SM04690-OA-21 was a phase 3, 16-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.

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.

02

Conditions studied

  • Knee Osteoarthritis
03

In context

Osteoarthritis, Knee

3,302 studies on the registry are indexed under Osteoarthritis, Knee; 608 are open to participants now.

This study's enrollment of 499 is above the median of 70 across 2,731 interventional studies indexed under Osteoarthritis, Knee.

Browse Osteoarthritis, Knee studies →

Lead sponsor

Biosplice Therapeutics, Inc. is the lead sponsor of 22 studies on the registry; none are open to participants now.

Of its 18 completed or terminated interventional studies of FDA-regulated products, 12 (67%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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)
  • Radiographic disease Stage 2 or 3 in target knee within 24 weeks of the Screening Visit according to the Kellgren-Lawrence (KL) grading of knee OA as assessed by independent central readers
  • Qualifying mean score on the 24-h average pain score (0-10 numeric rating scale)
  • Pain compatible with OA of the knee(s) for at least 26 weeks prior to the Screening Visit
  • Primary source of pain throughout the body is due to OA in the target knee
  • Body mass index (BMI) ≤ 35 kg/m2 at the Screening Visit

Exclusion criteria

Exclusion Criteria:

  • 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 the Screening Visit or Day 1
  • 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)
  • 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 allowed
  • Previous treatment with lorecivivint (SM04690)
  • Participation in a clinical research trial that included the receipt of an investigational product or any experimental therapeutic procedure within 26 weeks prior to the Screening Visit, or planned participation in any such trial
  • Subjects requiring the use of opioids > 1x per week within 12 weeks prior to Day 1
  • 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 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
  • Use of APAP or NSAIDs during washout period (between Screening Visit 2 and Day 1). Use of aspirin (up to 325 mg/day) for thrombosis prophylaxis is permitted.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
499 participants (actual)

Study arms

  • Experimental
    Lorecivivint

    Healthcare professional-administered intra-articular injection; performed on Day 1.

    Drug: Lorecivivint

  • Placebo comparator
    Vehicle

    Healthcare professional-administered intra-articular injection; performed on Day 1.

    Drug: Placebo

Interventions

  • DrugLorecivivint

    One intra-articular injection of 0.07 mg lorecivivint in 2 mL vehicle

    Also known as: SM04690

  • DrugPlacebo

    One intra-articular injection of 0 mg lorecivivint in 2 mL vehicle

    Also known as: Vehicle

06

What researchers measure

Primary outcomes

  1. Change From Baseline OA Pain in the Target Knee as Assessed by Weekly Average of Daily Pain Numeric Rating Scale (NRS) at Week 12

    Evaluate change from baseline OA pain in the target knee as assessed by weekly average of daily pain NRS at Week 12. 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 indicates pain as bad as you can imagine.

    Time frame: Baseline to Week 12

Secondary outcomes

  1. Change From Baseline OA Function as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscore (WOMAC Function) at Week 12

    Evaluate change from baseline OA function as assessed by WOMAC Function at Week 12. 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 NRS scale \[0-10\], where 0 indicates no pain / no stiffness / no difficulty, and 10 indicates extreme pain / extreme stiffness / extreme difficulty. For analysis, WOMAC Function scores were scaled to 0 to 100, where 0 represents "No Functional Difficulty" and 100 represents "Extreme Functional Difficulty".

    Time frame: Baseline and Week 12

  2. Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment at Week 12

    Evaluate change from baseline OA disease activity as assessed by Patient Global Assessment at Week 12. The Patient Global Assessment is an 11-point NRS \[0-10\] for subject self-reporting of how they feel their target knee is impacting them. For analysis, PGA scores were scaled to 0 to 100, where 0 represents "Very Good" and 100 represents "Very Bad".

    Time frame: Baseline and Week 12

07

Results

Posted Sep 1, 2026
Limitations and caveats
Hispanic/Latino subjects constituted \~65% of the study population primarily enrolled by 10 sites in the Miami, FL region. This observed Hispanic/Latino proportion is significantly higher than the overall Hispanic population suffering from knee OA (estimated at approximately 14% \[Deshpande BR et al. Arthritis Care Res 2016;68(12):1743-1750\]). Given the unusually high percentage of Hispanic/Latino participants, post-hoc efficacy analysis was conducted for non-Hispanic/Latino subjects only.

Participant flow

Participant flow — Overall Study
MilestoneLorecivivintVehicle
Started247252
Treated245251
Completed232243
Not completed159
Withdrew: Discontinue before study treatment administration21
Withdrew: Adverse event01
Withdrew: Lack of efficacy10
Withdrew: Lost to follow-up23
Withdrew: Site terminated by sponsor01
Withdrew: Subject non-compliance10
Withdrew: Withdrawal by subject for reason other than lack of efficacy73
Withdrew: Subject couldn't complete visit within specified window20

Outcome measures

PrimaryChange From Baseline OA Pain in the Target Knee as Assessed by Weekly Average of Daily Pain Numeric Rating Scale (NRS) at Week 12

Evaluate change from baseline OA pain in the target knee as assessed by weekly average of daily pain NRS at Week 12. 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 indicates pain as bad as you can imagine.

Time frame:
Baseline to Week 12
Reported as:
Mean · score on a scale
Change From Baseline OA Pain in the Target Knee as Assessed by Weekly Average of Daily Pain Numeric Rating Scale (NRS) at Week 12
score on a scaleLorecivivintVehicle
Change From Baseline OA Pain in the Target Knee as Assessed by Weekly Average of Daily Pain Numeric Rating Scale (NRS) at Week 12-3.64 ± 2.44-3.54 ± 2.45
Statistical analysis
  • Lorecivivint vs Vehicle · Mixed Models Analysis · p = 0.543 (The familywise error rate will be controlled in the strong sense using the closed, fixed sequence testing method evaluated in the following sequential order: H1: Pain NRS H2: WOMAC Function H3: Patient Global) · Mean difference (final values): -0.12 · 95% CI -0.53 to 0.28Estimate was calculated as Lorecivivint - Placebo. A negative value indicates more improvement in the Lorecivivint compared to Placebo.
SecondaryChange From Baseline OA Function as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscore (WOMAC Function) at Week 12

Evaluate change from baseline OA function as assessed by WOMAC Function at Week 12. 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 NRS scale \[0-10\], where 0 indicates no pain / no stiffness / no difficulty, and 10 indicates extreme pain / extreme stiffness / extreme difficulty. For analysis, WOMAC Function scores were scaled to 0 to 100, where 0 represents "No Functional Difficulty" and 100 represents "Extreme Functional Difficulty".

Time frame:
Baseline and Week 12
Reported as:
Mean · score on a scale
Change From Baseline OA Function as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscore (WOMAC Function) at Week 12
score on a scaleLorecivivintVehicle
Change From Baseline OA Function as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscore (WOMAC Function) at Week 12-29.28 ± 23.45-28.65 ± 24.40
Statistical analysis
  • Lorecivivint vs Vehicle · Mixed Models Analysis · p = 0.977 (The familywise error rate will be controlled in the strong sense using the closed, fixed sequence testing method evaluated in the following sequential order: H1: Pain NRS H2: WOMAC Function H3: Patient Global) · Mean difference (final values): 0.06 · 95% CI -4.16 to 4.28Estimate was calculated as Lorecivivint - Placebo. A negative value indicates more improvement in the Lorecivivint compared to Placebo.
SecondaryChange From Baseline OA Disease Activity as Assessed by Patient Global Assessment at Week 12

Evaluate change from baseline OA disease activity as assessed by Patient Global Assessment at Week 12. The Patient Global Assessment is an 11-point NRS \[0-10\] for subject self-reporting of how they feel their target knee is impacting them. For analysis, PGA scores were scaled to 0 to 100, where 0 represents "Very Good" and 100 represents "Very Bad".

Time frame:
Baseline and Week 12
Reported as:
Mean · score on a scale
Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment at Week 12
score on a scaleLorecivivintVehicle
Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment at Week 12-33.84 ± 26.55-33.33 ± 28.21
Statistical analysis
  • Lorecivivint vs Vehicle · Mixed Models Analysis · p = 0.985 (The familywise error rate will be controlled in the strong sense using the closed, fixed sequence testing method evaluated in the following sequential order: H1: Pain NRS H2: WOMAC Function H3: Patient Global) · Mean difference (final values): 0.04 · 95% CI -5.73 to 3.25Estimate was calculated as Lorecivivint - Placebo. A negative value indicates more improvement in the Lorecivivint compared to Placebo.
Post-hocChange From Baseline in OA Pain in the Target Knee (Pain NRS) for Sites for Non-Hispanic/Latino Subjects

Evaluate change from baseline OA pain in the target knee as assessed by the weekly averages of daily pain Numeric Rating Scale (NRS) for non-Hispanic/Latino subjects. 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.

Time frame:
Baseline and Week 12
Reported as:
Mean · score on a scale
Change From Baseline in OA Pain in the Target Knee (Pain NRS) for Sites for Non-Hispanic/Latino Subjects
score on a scaleLorecivivintVehicle
Change From Baseline in OA Pain in the Target Knee (Pain NRS) for Sites for Non-Hispanic/Latino Subjects-3.14 ± 2.25-2.51 ± 2.10
Statistical analysis
  • Lorecivivint vs Vehicle · ANCOVA · p = 0.100 · Mean difference (final values): -0.56 · 95% CI -1.24 to 0.11Estimate was calculated as Lorecivivint - Placebo. A negative value indicates more improvement in the Lorecivivint compared to Placebo.

Adverse events

Collected over AEs were assessed at each in-person study visit from the time of study medication injection on Day 1 through Week 16 (EOS) or Early Termination.. Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Lorecivivint0/242 (0%)2/242 (0.8%)37/242 (15.3%)
Vehicle0/249 (0%)3/249 (1.2%)26/249 (10.4%)
Most frequent serious events
Most frequent serious events
EventLorecivivintVehicle
Non-cardiac chest painGeneral disorders1/2420/249
Cholecystitis acuteHepatobiliary disorders1/2420/249
Angina pectorisCardiac disorders0/2421/249
Hip fractureInjury, poisoning and procedural complications0/2421/249
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders0/2421/249
Most frequent other events
Most frequent other events
EventLorecivivintVehicle
HeadacheNervous system disorders15/24210/249
Back painMusculoskeletal and connective tissue disorders3/24211/249
NasopharyngitisInfections and infestations6/2428/249
ArthralgiaMusculoskeletal and connective tissue disorders7/2426/249
DiarrhoeaGastrointestinal disorders7/2423/249
InfluenzaInfections and infestations5/2420/249

Baseline characteristics

The Full Analysis Set (FAS) includes all subjects who were randomized and received a study injection. The FAS is used to describe the analysis set which is as complete as possible and as close as possible to the intent-to-treat ideal of including all randomized subjects. Subjects will be analyzed as randomized for the FAS.

Age, Continuous
Age, Continuous(years)LorecivivintVehicleTotal
Mean60.4 ± 8.761.3 ± 9.260.9 ± 9.0
Sex: Female, Male
Sex: Female, Male(Participants)LorecivivintVehicleTotal
Female156154310
Male8695181
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)LorecivivintVehicleTotal
Hispanic or Latino158158316
Not Hispanic or Latino8390173
Unknown or Not Reported112
Race (NIH/OMB)
Race (NIH/OMB)(Participants)LorecivivintVehicleTotal
American Indian or Alaska Native101
Asian257
Native Hawaiian or Other Pacific Islander101
Black or African American464591
White188196384
More than one race437
Unknown or Not Reported000
Body Mass Index
Body Mass Index(kg / m^2)LorecivivintVehicleTotal
Mean29.21 ± 3.7028.87 ± 3.8229.04 ± 3.76
Kellgren-Lawrence Grade
Kellgren-Lawrence Grade(Participants)LorecivivintVehicleTotal
Grade 2242246488
Grade 3033
08

Study locations

44 sites
  • Tucson Orthopaedic Institute
    Tucson, Arizona 85712, United States
  • Core Healthcare Research
    Cerritos, California 90703, United States
  • BioSolutions Clinical Research Center
    La Mesa, California 91942, United States
  • Infinity Clinical Research
    Norco, California 92860, United States
  • Dream Team Clinical Research
    Pomona, California 91767, United States
  • Artemis Institute for Clinical Research
    San Diego, California 92103, United States
  • Encompass Clinical Research
    Spring Valley, California 97978, United States
  • Millennium Clinical Trials, LLC
    Thousand Oaks, California 91360, United States
  • Unique Clinical Trials
    Doral, Florida 33172, United States
  • Eastern Research, Inc.
    Hialeah, Florida 33013, United States
  • TecTum Research
    Hollywood, Florida 33024, United States
  • Columbus Clinical Services, LLC
    Miami, Florida 33125, United States
  • AppleMed Research Group, LLC
    Miami, Florida 33126, United States
  • Advance Medical Research Center
    Miami, Florida 33135, United States
  • Health and Life Research Institute, LLC
    Miami, Florida 33155, United States
  • BioMed Research and Medical Center
    Miami, Florida 33156, United States
  • Well Pharma Medical Research, Corp
    Miami, Florida 33173, United States
  • South Florida Research Phase I-IV, Inc.
    Miami Springs, Florida 33166, United States
  • Tampa Pain Relief Center
    Tampa, Florida 33603, United States
  • Premier Medical Associates
    The Villages, Florida 32159, United States
  • Conquest Research, LLC
    Winter Park, Florida 32789, United States
  • Pinnacle Trials, Inc.
    Stockbridge, Georgia 30281, United States
  • Chicago Clinical Research Institute
    Chicago, Illinois 60607, United States
  • MediSphere Medical Research Center, LLC
    Evansville, Indiana 47714, United States
  • DelRicht Research - Mandeville
    Mandeville, Louisiana 70471, United States
  • DelRicht Research
    New Orleans, Louisiana 70124, United States
  • DelRicht Research - Prairieville
    Prairieville, Louisiana 70817, United States
  • DelRicht Research - Rockville
    Rockville, Maryland 20852, United States
  • Skylight Health Research
    Burlington, Massachusetts 01803, United States
  • Oakland Medical Research
    Troy, Michigan 48085, United States
  • Healthcare Research Network
    Hazelwood, Missouri 63042, United States
  • Albuquerque Clinical Trials
    Albuquerque, New Mexico 87102, United States
  • Hightop Medical Research Center
    Cincinnati, Ohio 45224, United States
  • Conrad Clinical Research
    Edmond, Oklahoma 73013, United States
  • DelRicht Research - Tulsa
    Tulsa, Oklahoma 74133, United States
  • Clinical Trials of South Carolina
    Charleston, South Carolina 29406, United States
  • Piedmont Research Partners, LLC
    Fort Mill, South Carolina 29707, United States
  • Health Concepts
    Rapid City, South Dakota 57702, United States
  • Zenos Clinical Research
    Dallas, Texas 75230, United States
  • Synergy Groups Medical, LLC
    Houston, Texas 77036, United States
  • Synergy Groups Medical, LLC
    Houston, Texas 77061, United States
  • Clinical Investigations of Texas
    Plano, Texas 75075, United States
  • Diagnostic Research Group
    San Antonio, Texas 78229, United States
  • Wasatch Clinical Research, LLC
    Salt Lake City, Utah 84107, United States
09

References and documents

Study documents

  • Study protocol · Nov 9, 2022
  • Statistical analysis plan · Apr 1, 2024

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 1, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT05603754
Lead sponsor
Biosplice Therapeutics, Inc.
Collaborators
NBCD A/S
Responsible party
Sponsor
First posted
Nov 3, 2022
Start date
Nov 18, 2022
Primary completion
Feb 20, 2024
Completion
Feb 20, 2024
Results posted
Sep 1, 2026
Last update
Sep 1, 2026

Study contacts

Yusuf Yazici, MD
study director · Biosplice Therapeutics, Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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