MRI Study to Evaluate the Safety and Efficacy of SM04690 for Knee Osteoarthritis

NCT03706521 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: SM04690-OA-08
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study was to evaluate the safety and efficacy of lorecivivint (LOR) injected in the target knee joint of moderately to severely symptomatic osteoarthritis (OA) subjects. Efficacy was primarily evaluated via magnetic resonance imaging (MRI).

Conditions

Knee Osteoarthritis

Keywords

SM04690; Wnt pathway inhibitor; osteoarthritis; lorecivivint; Biosplice Therapeutics, Inc.

Outcome Measures

Primary Outcomes (4)

• Change From Baseline in Medial Tibial Cartilage Thickness in the Target Knee as Measured by MRI

  The assessment of hyaline cartilage thickness present in the knee joint can be useful in evaluating cartilage health. Cartilage thickness decreases may indicate knee osteoarthritis progression. Cartilage thickness was measured using a semi-automated Local-Area Cartilage Segmentation (LACS) software for knee cartilage segmentation of knee MRI. The LACS coordinate system is based on anatomical bony landmarks and permits measurement within any subregion of the femorotibial joint consistently across longitudinal assessments.

  Baseline and Week 26

• Change From Baseline in Medial Tibial Cartilage Volume in the Target Knee as Measured by MRI

  The assessment of hyaline cartilage volume present in the knee joint can be useful in evaluating cartilage health. Cartilage volume decreases may indicate knee osteoarthritis progression. Cartilage volume was measured using a semi-automated Local-Area Cartilage Segmentation (LACS) software for knee cartilage segmentation of knee MRI. The LACS coordinate system is based on anatomical bony landmarks and permits measurement within any subregion of the femorotibial joint consistently across longitudinal assessments.

  Baseline and Week 26

• Change From Baseline in Average T1 Rho for the Medial Tibial Cartilage of Target Knee

  T1rho mapping refers to an investigational magnetic resonance imaging technique that measures the low-frequency interactions between macromolecules such as proteoglycan and glycosaminoglycan and water, useful for evaluating cartilage health. Increase in T1rho measurements over time can represent cartilage degeneration.

  Baseline and Week 26

• Change From Baseline in Average T2 Mapping in Medial Tibial Cartilage of Target Knee

  T2 mapping refers to an investigational magnetic resonance imaging technique that measures biochemical changes in cartilage, including the integrity of collagen network, and collagen and water content, useful for evaluating cartilage health. Increase in T2 mapping measurements over time can represent cartilage degeneration.

  Baseline and Week 26

Study Arms (1)

Lorecivivint 0.07 mg

EXPERIMENTAL

Single intra-articular injection of lorecivivint (SM04690) 0.07 mg in 2 mL vehicle lorecivivint: Healthcare professional-administered intra-articular injection performed once on Day 1 of the study.

Drug: lorecivivint

Interventions

lorecivivint DRUG

Healthcare professional-administered intra-articular injection performed once on Day 1 of the study.

Also known as: SM04690

Lorecivivint 0.07 mg

Eligibility Criteria

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

You may qualify if:

• 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)
• 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
• Daily OA knee pain diary average Numeric Rating Scale (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
• Pain NRS scores recorded for the target knee on at least 4 out of the 7 days immediately preceding Day 1
• Daily OA knee pain diary average NRS intensity score \<4 in the non-target knee on the 11-point (0-10) NRS scale for the 7 days immediately preceding Day 1
• Pain NRS scores recorded for the non-target knee on at least 4 out of the 7 days immediately preceding Day 1
• Baseline mJSW by radiograph between 2 and 4 mm, inclusive, in the target knee at the Screening Visit as assessed by independent central readers
• Total WOMAC score of 96-192 (out of 240) for the target knee at Day 1 regardless of if the subject is on symptomatic oral treatment
• Negative drug test for amphetamine, methamphetamine, buprenorphine, cocaine, methadone, opiates, phencyclidine (PCP), propoxyphene, barbiturates, benzodiazepine, methaqualone, and tricyclic antidepressants, except if any such drugs are clinically indicated and allowed by the protocol at the Screening Visit
• Subjects with depression or anxiety must be clinically stable for 12 weeks prior to the Screening Visit and, if on treatment for depression or anxiety, be on 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, and must have signed it prior to any study-related procedure being performed
• Subject's Screening Visit must occur while enrollment into the study is open

You may not qualify if:

• Women who are pregnant, lactating, or have a positive pregnancy test result at the Screening Visit
• Women of childbearing potential who are sexually active, and who are not willing to use an acceptable method of birth control during the study period
• Men of childbearing potential who are sexually active and have a partner who is capable of becoming pregnant, neither of whom are agreeable to using an acceptable method of birth control during the study period
• Body mass index (BMI) \> 40
• Partial or complete joint replacement in either knee
• Currently requires: a) regular use (in the opinion of the Investigator) of ambulatory assistive devices (e.g., wheelchair, parallel bars, walker, canes, or crutches), or b) use of a lower extremity prosthesis, and/or a structural knee brace (i.e., a knee brace that contains hardware)
• Radiographic disease Stage 0, 1, or 4 in the target knee at the Screening Visit according to the Kellgren-Lawrence (KL) grading of knee OA as assessed by independent central readers
• Previous treatment with lorecivivint (SM04690)
• Subjects who have previously failed screening on this protocol and fail to meet re-screening criteria
• Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to the Screening Visit
• Any surgery scheduled during the study period. Non-surgical invasive procedures conducted for a diagnostic or therapeutic purpose scheduled during the study period are not prohibited
• Significant and clinically evident misalignment of either knee that would impact subject function, as determined by the Investigator
• History of malignancy within the last 5 years; however, subjects with prior history of in situ basal or squamous cell skin cancer are eligible if completely excised. Subjects with other malignancies are eligible if they have been continuously disease free for at least 5 years prior to the Screening Visit
• Clinically significant abnormal screening hematology values, blood chemistry values, or urinalysis values as determined by the Investigator
• Any condition, including laboratory findings not included in the Screening Visit laboratory tests and findings in the medical history or in the pre-study assessments, 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

Sponsors & Collaborators

• Biosplice Therapeutics, Inc.: lead

Study Sites (1)

Research Site

San Francisco, California, 94158, United States

Location

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Interventions

lorecivivint

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Limitations and Caveats

Given the pilot nature of the study and the impact of COVID-19 pandemic-related issues on data completeness, limited conclusions can be drawn from this study.

Results Point of Contact

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

info@biosplice.com

858.926.2900

Study Officials

• Yusuf Yazici, M.D.

  Biosplice Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2018
• First Posted: October 16, 2018
• Study Start: March 11, 2019
• Primary Completion: July 22, 2020
• Study Completion: December 21, 2020
• Last Updated: March 4, 2026
• Results First Posted: March 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)