A Long-Term Safety and Efficacy Study of Lorecivivint in Subjects With Osteoarthritis of the Knee

NCT04520607 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: SM04690-OA-07
• Study Type: interventional
• Target: 276
• Locations: 1 country
• Sites: 42

Brief Summary

Study OA-07 was a randomized, double-blind, placebo-controlled, Phase 3, multicenter, 2-year clinical trial that enrolled subjects from the recently completed Study OA-11 (NCT03928184). The first 48 weeks of OA-07 the trial was placebo-controlled with subjects receiving the same randomized treatment received in OA-11. Investigators, research staff and subjects remained blinded to treatment allocation. At Week 48, all subjects were administered LOR in the open-label portion of the trial.

Conditions

Osteoarthritis, Knee

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Change From OA-11-study Baseline Medial Joint Space Width (mJSW) in the Target Knee

  Change from OA-11-study baseline in mJSW measured in millimeters as documented by radiograph (X-ray) of the target knee. JSW measurements were provided by a blinded, central imaging vendor using landmark-based, computer-assisted proprietary methodology.

  OA-11-study baseline; Visit 3E (Week 48)

• Change From OA-07-study Baseline OA Pain in the Target Knee

  Change from OA-07-study baseline OA pain the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain). The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals 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 a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Pain subscore ranges from 0 \[no pain\] to 100 \[pain as bad as it can be\].

  OA-07-study baseline; Visit 2E (Week 24)

• Change From OA-07-study Baseline OA Function in the Target Knee

  Change from OA-07-study baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) physical functioning subscore (WOMAC Function). The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals 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 a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Function subscore ranges from 0 \[highest functional status\] to 100 \[most impaired functional status\].

  OA-07-study baseline; Visit 2E (Week 24)

Secondary Outcomes (2)

• Change From OA-07-study Baseline OA Pain in the Target Knee

  OA-07-study baseline; Visit 3E (Week 48)

• Change From OA-07-study Baseline OA Function in the Target Knee

  OA-07-study baseline; Visit 3E (Week 48)

Other Outcomes (1)

• Change From OA-11-study Baseline Medial Joint Space Width (mJSW) in the Target Knee

  OA-11-study baseline; Visit 6E (Week 100)

Study Arms (2)

Lorecivivint

EXPERIMENTAL

Subjects assigned to this arm will receive one intra-articular injection of 0.07 mg lorecivivint in 2 ml vehicle (same treatment as in the parent-study) into their target knee (the same target knee injected in the parent study); performed on Day 1, at Week 48 and every 52 weeks thereafter.

Drug: Lorecivivint

Placebo

PLACEBO COMPARATOR

Subjects assigned to this arm will receive one intra-articular injection of 0 mg lorecivivint in 2 ml vehicle (same treatment as in the parent-study) into their target knee (the same target knee injected in the parent study) on Day 1, followed by one intra-articular injection of 0.07 mg lorecivivint in 2 ml vehicle at Week 48 and every 52 weeks thereafter.

Drug: Placebo; Drug: Lorecivivint

Interventions

Placebo DRUG

Healthcare professional-administered intra-articular injection of vehicle.

Also known as: Vehicle

Placebo

Lorecivivint DRUG

Healthcare professional-administered intra-articular injections of lorecivivint.

Also known as: SM04690

Lorecivivint; Placebo

Eligibility Criteria

• Age: 41 Years - 81 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Completion of the Study SM04690-OA-11 (NCT03928184)
• Compliance with procedures in study SM04690-OA-11, in the opinion of the Investigator
• Fully understanding study requirements and willingness to comply with study visits and assessments
• Understanding and signing of the informed consent form (ICF) prior to any study-related procedures

You may not qualify if:

• Any condition 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
• Any contraindications for an intra-articular (IA) injection in the target knee in the opinion of the Investigator
• Any known reason identified by the Investigator or Sponsor that the subject may not be compliant with study visits or may no longer be an appropriate candidate for the study (e.g. planned major surgery, knee replacement during the parent study, planning to move away from the research site, or initiation of a prohibited concomitant medication including, but not limited to, IA injection of glucocorticoids, hyaluronic acid derivatives, platelet-rich plasma, stem cell therapies, or other agents with therapeutic intent into the target knee)
• Participation in a clinical research trial (other than the prior SM04690-OA-11 study) that included the receipt of an investigational product (IP) or any experimental therapeutic procedure within 12 weeks before any study injection, or planned participation in any such trial
• Current or pending disability claim, workers' compensation, or litigation(s) that may compromise response to treatment
• 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 Visit 1E (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 (as outlined in the protocol) during the study period

Sponsors & Collaborators

• Biosplice Therapeutics, Inc.: lead

Study Sites (42)

Research Site

Tucson, Arizona, 85712, United States

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Anaheim, California, 92805, 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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Thousand Oaks, California, 91360, United States

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Denver, Colorado, 80209, United States

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Hialeah, Florida, 33016, 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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Port Orange, Florida, 32127, 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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Newnan, Georgia, 30265, United States

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Woodstock, Georgia, 30189, 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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Valparaiso, Indiana, 46383, United States

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New Orleans, Louisiana, 70124, 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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Omaha, Nebraska, 68114, 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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Rochester, New York, 14609, United States

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Charlotte, North Carolina, 28209, 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, 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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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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Carrollton, Texas, 75007, United States

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Plano, Texas, 75075, United States

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San Antonio, Texas, 78229, United States

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Draper, Utah, 84020, United States

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Salt Lake City, Utah, 84107, United States

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Charlottesville, Virginia, 22911, United States

Location

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Interventions

lorecivivint

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Results Point of Contact

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

info@biosplice.com

858-926-2900

Study Officials

• Ismail Simsek, MD

  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
• Masking Details: The first 48 weeks were research site personnel (investigator, coordinators, assessors) and subjects were blinded to the treatment assignment. After Week 48, the remainder of the study was open-label with all subjects receiving LOR study injections.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2020
• First Posted: August 20, 2020
• Study Start: August 25, 2020
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: March 24, 2026
• Results First Posted: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (42)