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

NCT ID: NCT04385303

Last Updated: 2026-02-04

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

496 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-26

Study Completion Date

2021-09-08

Brief Summary

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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.

Detailed Description

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SM04690-OA-10 was a phase 3, 28-week multicenter, randomized, double-blind, placebo-controlled, parallel group study investigating the safety, tolerability and efficacy of lorecivivint 0.07 mg (compared with placebo) 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.

Conditions

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Knee Osteoarthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Vehicle

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

Group Type ACTIVE_COMPARATOR

Placebo

Intervention Type DRUG

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

Lorecivivint

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

Group Type EXPERIMENTAL

Lorecivivint

Intervention Type DRUG

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

Interventions

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Lorecivivint

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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SM04690 Vehicle

Eligibility Criteria

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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
* 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

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
* 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
Minimum Eligible Age

40 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Biosplice Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yusuf Yazici, M.D.

Role: STUDY_DIRECTOR

Biosplice Therapeutics, Inc.

Locations

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Research Site

Birmingham, Alabama, United States

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Birmingham, Alabama, United States

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Mobile, Alabama, United States

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Phoenix, Arizona, United States

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Little Rock, Arkansas, United States

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Anaheim, California, United States

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Beverly Hills, California, United States

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Canoga Park, California, United States

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Garden Grove, California, United States

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La Mesa, California, United States

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Norco, California, United States

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Pomona, California, United States

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San Diego, California, United States

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Santa Monica, California, United States

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Thousand Oaks, California, United States

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Westminster, California, United States

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Boulder, Colorado, United States

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Hamden, Connecticut, United States

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Clearwater, Florida, United States

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Edgewater, Florida, United States

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Gulf Breeze, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami Lakes, Florida, United States

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Sunrise, Florida, United States

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Sweetwater, Florida, United States

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West Palm Beach, Florida, United States

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Winter Haven, Florida, United States

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Winter Park, Florida, United States

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Marietta, Georgia, United States

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Newnan, Georgia, United States

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Woodstock, Georgia, United States

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Boise, Idaho, United States

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Chicago, Illinois, United States

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Gurnee, Illinois, United States

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Oak Brook, Illinois, United States

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Evansville, Indiana, United States

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Greenwood, Indiana, United States

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Valparaiso, Indiana, United States

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New Orleans, Louisiana, United States

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Wheaton, Maryland, United States

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Boston, Massachusetts, United States

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Troy, Michigan, United States

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Hazelwood, Missouri, United States

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Kansas City, Missouri, United States

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St Louis, Missouri, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Las Vegas, Nevada, United States

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Reno, Nevada, United States

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Freehold, New Jersey, United States

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Albuquerque, New Mexico, United States

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Hartsdale, New York, United States

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Rochester, New York, United States

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Greensboro, North Carolina, United States

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Salisbury, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Cincinnati, Ohio, United States

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Edmond, Oklahoma, United States

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Duncansville, Pennsylvania, United States

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Charleston, South Carolina, United States

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Fort Mill, South Carolina, United States

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Mt. Pleasant, South Carolina, United States

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Rapid City, South Dakota, United States

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Bellaire, Texas, United States

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Carrollton, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Plano, Texas, United States

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Draper, Utah, United States

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Ogden, Utah, United States

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Salt Lake City, Utah, United States

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Charlottesville, Virginia, United States

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Richmond, Virginia, United States

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Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 39495154 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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SM04690-OA-10

Identifier Type: -

Identifier Source: org_study_id

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