Patient-Reported Outcomes in Evaluating Lorecivivint (SM04690) for Moderate to Severe Knee Osteoarthritis (STRIDES-1)

NCT04385303 | Completed Phase 3 Results FDA Drug

• 1 other identifier: SM04690-OA-10
• Study Type: interventional
• Target: 496
• Locations: 1 country
• Sites: 76

Brief Summary

This phase 3 study is a multicenter, randomized, double-blind, placebo-controlled study of lorecivivint injected intraarticularly (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 patient reported outcomes (PROs) to evaluate the safety and efficacy of lorecivivint.

Conditions

Knee Osteoarthritis

Keywords

SM04690; Wnt pathway inhibitor; osteoarthritis; Samumed; lorecivivint

Outcome Measures

Primary Outcomes (1)

• Change From Baseline OA Pain in the Target Knee as Assessed by the 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 the 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 represents the worst possible pain.

  Baseline and Week 12

Secondary Outcomes (5)

• Change From Baseline OA Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS) at Week 24

  Baseline and Week 24

• 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) at Week 12

  Baseline and Week 12

• 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) at Week 24

  Baseline and Week 24

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

  Baseline and Week 12

• Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment at Week 24

  Baseline and Week 24

Study Arms (2)

Vehicle

ACTIVE COMPARATOR

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

Drug: Placebo

Lorecivivint

EXPERIMENTAL

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

Drug: Lorecivivint

Interventions

Lorecivivint DRUG

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

Also known as: SM04690

Lorecivivint

Placebo DRUG

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

Also known as: Vehicle

Vehicle

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• Significant malalignment of anatomical axis (medial angle formed by the femur and tibia) of the target knee (varus \> 10°, valgus \> 10°) by radiograph within 24 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)
• 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)
• Subjects who have previously failed screening on this protocol and fail to meet re-screening criteria
• 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

Sponsors & Collaborators

• Biosplice Therapeutics, Inc.: lead

Study Sites (76)

Research Site

Birmingham, Alabama, 35205, United States

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Birmingham, Alabama, 35215, United States

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Mobile, Alabama, 36608, United States

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Phoenix, Arizona, 85018, United States

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Phoenix, Arizona, 85053, United States

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Tucson, Arizona, 85712, United States

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Little Rock, Arkansas, 72205, United States

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Anaheim, California, 92805, United States

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Beverly Hills, California, 90211, United States

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Canoga Park, California, 91303, United States

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Garden Grove, California, 92840, United States

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La Mesa, California, 91942, United States

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Norco, California, 92860, United States

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Pomona, California, 91767, United States

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San Diego, California, 92103, United States

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Santa Monica, California, 90404, United States

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Thousand Oaks, California, 91360, United States

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Westminster, California, 92683, United States

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Boulder, Colorado, 80301, United States

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Hamden, Connecticut, 06517, United States

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Clearwater, Florida, 33761, United States

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Edgewater, Florida, 32132, United States

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Gulf Breeze, Florida, 32561, United States

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Miami, Florida, 33125, United States

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Miami, Florida, 33173, United States

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Miami Lakes, Florida, 33014, United States

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Sunrise, Florida, 33351, United States

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Sweetwater, Florida, 33172, United States

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West Palm Beach, Florida, 33409, United States

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Winter Haven, Florida, 33880, United States

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Winter Park, Florida, 32789, United States

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Marietta, Georgia, 30060, United States

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Newnan, Georgia, 30265, United States

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Woodstock, Georgia, 30189, United States

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Boise, Idaho, 83713, United States

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Chicago, Illinois, 60607, United States

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Gurnee, Illinois, 60031, United States

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Oak Brook, Illinois, 60523, United States

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Evansville, Indiana, 47714, United States

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Greenwood, Indiana, 46143, United States

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Valparaiso, Indiana, 46383, United States

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New Orleans, Louisiana, 70124, United States

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Wheaton, Maryland, 20902, United States

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Boston, Massachusetts, 02111, United States

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Troy, Michigan, 48085, United States

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Hazelwood, Missouri, 63042, United States

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Kansas City, Missouri, 64114, United States

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St Louis, Missouri, 63141, United States

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St Louis, Missouri, 63141, United States

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Omaha, Nebraska, 68114, United States

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Las Vegas, Nevada, 89119, United States

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Reno, Nevada, 89519, United States

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Freehold, New Jersey, 07728, United States

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Albuquerque, New Mexico, 87102, United States

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Hartsdale, New York, 10530, United States

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Rochester, New York, 14642, United States

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Greensboro, North Carolina, 27408, United States

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Salisbury, North Carolina, 28144, United States

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Winston-Salem, North Carolina, 27103, United States

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Cincinnati, Ohio, 45224, United States

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Edmond, Oklahoma, 73013, United States

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Duncansville, Pennsylvania, 16635, United States

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Charleston, South Carolina, 29406, United States

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Fort Mill, South Carolina, 29707, United States

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Mt. Pleasant, South Carolina, 29464, United States

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Rapid City, South Dakota, 57702, United States

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Bellaire, Texas, 77401, United States

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Carrollton, Texas, 75007, United States

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Dallas, Texas, 75231, United States

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Houston, Texas, 77029, United States

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Plano, Texas, 75075, United States

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Draper, Utah, 84020, United States

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Ogden, Utah, 84405, United States

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Salt Lake City, Utah, 84107, United States

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Charlottesville, Virginia, 22911, United States

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Richmond, Virginia, 23219, United States

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Related Publications (1)

• 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.

  PMID: 39495154 DERIVED

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Interventions

lorecivivint

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Limitations and Caveats

This trial was conducted during COVID-19 and its confounding effects on clinical outcomes in knee OA patients based on observational data have been reported (Knee Surg Sports Traumatol Arthrosc, 2020;28(8):2435-43). Structural progression enrichment in the OA-11 trial, which enrolled concurrently, might have confounded short-term therapeutic pain detection; this hypothesis was evaluated in the post-hoc Kellgren-Lawrence Grade 2 only analysis.

Results Point of Contact

• Title: Christopher Swearingen, PhD, VP of Biometrics
• Organization: Biosplice Therapeutics

chris.swearingen@biosplice.com

858.926.2952

Study Officials

• Yusuf Yazici, M.D.

  Biosplice Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2020
• First Posted: May 12, 2020
• Study Start: May 26, 2020
• Primary Completion: September 8, 2021
• Study Completion: September 8, 2021
• Last Updated: February 4, 2026
• Results First Posted: February 4, 2026

Record last verified: 2026-01

Locations

US (76)