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

NCT03928184 | Completed Phase 3 Results FDA Drug

• 1 other identifier: SM04690-OA-11
• Study Type: interventional
• Target: 501
• Locations: 1 country
• Sites: 99

Brief 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. This study will utilize radiographs and 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 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 Outcomes (8)

• Change From Baseline in OA Pain in the Target Knee (Pain NRS)

  Baseline and Week 24

• Change From Baseline in OA Pain in the Target Knee (Pain NRS)

  Baseline and Week 52

• Change From Baseline in OA Function in the Target Knee (WOMAC Function)

  Baseline and Week 12

• Change From Baseline in OA Function in the Target Knee (WOMAC Function)

  Baseline and Week 24

• Change From Baseline in OA Function in the Target Knee (WOMAC Function)

  Baseline and Week 52

Other Outcomes (1)

• Change From Baseline in Medial Joint Space Width (mJSW) in the Target Knee

  Baseline and Week 52

Study Arms (2)

0.07 mg lorecivivint

EXPERIMENTAL

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

Drug: Lorecivivint

Vehicle

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Placebo DRUG

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

Also known as: Vehicle

Vehicle

Lorecivivint DRUG

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

Also known as: SM04690

0.07 mg lorecivivint

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)
• 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
• 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)

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Biosplice Therapeutics, Inc.: lead

Study Sites (99)

Research Site

Birmingham, Alabama, 35205, United States

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Birmingham, Alabama, 35215, United States

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Birmingham, Alabama, 35216, United States

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Peoria, Arizona, 85381, United States

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Phoenix, Arizona, 85037, 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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Garden Grove, California, 92840, 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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San Marcos, California, 92078, United States

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Spring Valley, California, 91978, United States

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Westminster, California, 92683, United States

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Boulder, Colorado, 80301, United States

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Colorado Springs, Colorado, 80918, United States

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Denver, Colorado, 80209, United States

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Waterbury, Connecticut, 06708, United States

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Clearwater, Florida, 33761, United States

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Coral Gables, Florida, 33134, United States

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Hialeah, Florida, 33016, United States

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Miami, Florida, 33143, United States

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Miami Lakes, Florida, 33014, United States

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Orlando, Florida, 32806, United States

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Oviedo, Florida, 32765, United States

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Port Orange, Florida, 32127, United States

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Sunrise, Florida, 33351, 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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Research Site #1

Winter Park, Florida, 32789, 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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Stockbridge, Georgia, 30281, United States

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Woodstock, Georgia, 30189, United States

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Boise, Idaho, 83713, United States

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Meridian, Idaho, 83642, United States

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Bloomington, Illinois, 61704, 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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Rockford, Illinois, 61114, United States

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Anderson, Indiana, 46011, United States

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Evansville, Indiana, 47714, United States

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Valparaiso, Indiana, 46383, United States

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Kansas City, Kansas, 66160, United States

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Wichita, Kansas, 67205, United States

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Monroe, Louisiana, 71203, 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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Bay City, Michigan, 48706, United States

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Troy, Michigan, 48085, United States

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Hazelwood, Missouri, 63042, United States

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St Louis, Missouri, 63141, United States

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La Vista, Nebraska, 68128, United States

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Lincoln, Nebraska, 68516, United States

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Omaha, Nebraska, 68114, United States

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Albuquerque, New Mexico, 87108, United States

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Great Neck, New York, 11021, United States

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Hartsdale, New York, 10530, United States

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New York, New York, 10016, United States

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New York, New York, 10021, United States

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New York, New York, 10021, United States

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Rochester, New York, 14609, United States

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Williamsville, New York, 14221, United States

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Charlotte, North Carolina, 28209, United States

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Leland, North Carolina, 28451, 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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Fargo, North Dakota, 58104, United States

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Cincinnati, Ohio, 45219, United States

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Cincinnati, Ohio, 45224, United States

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Cincinnati, Ohio, 45242, United States

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Columbus, Ohio, 43235, United States

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Oklahoma City, Oklahoma, 73103, United States

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Oklahoma City, Oklahoma, 73112, United States

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Duncansville, Pennsylvania, 16635, United States

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Fort Mill, South Carolina, 29707, United States

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Greenville, South Carolina, 29607, United States

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Greer, South Carolina, 29651, 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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Austin, Texas, 78745, United States

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Bedford, Texas, 76021, United States

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Carrollton, Texas, 75007, United States

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Dallas, Texas, 75231, United States

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Edinburg, Texas, 78539, United States

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Houston, Texas, 77029, United States

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Houston, Texas, 77055, United States

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Plano, Texas, 75075, United States

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San Antonio, Texas, 78215, United States

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San Antonio, Texas, 78229, United States

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San Antonio, Texas, 78258, United States

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Draper, Utah, 84020, United States

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Murray, Utah, 84123, 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, leading to a severely damaged OA population in the OA-11 trial, might have confounded short-term therapeutic pain detection and repeat dosing may be required to demonstrate clinical benefit in severely damaged OA populations.

Results Point of Contact

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

info@biosplice.com

858.926.2900

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: April 23, 2019
• First Posted: April 26, 2019
• Study Start: May 17, 2019
• Primary Completion: August 20, 2021
• Study Completion: August 20, 2021
• Last Updated: February 13, 2026
• Results First Posted: February 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (99)