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

Osteoarthritis, Knee Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04520607
• Other study ID #: SM04690-OA-07
• Status: Completed
• Phase: Phase 3
• Start date: August 25, 2020
• Est. completion date: June 30, 2023

Study information

• Verified date: December 2023
• Source: Biosplice Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed as a long-term extension to the Phase 3 parent-study SM04690-OA-11. It aims to evaluate the safety and efficacy of long-term use of lorecivivint (LOR) in subjects with knee osteoarthritis (OA). The first 48 weeks will be single-blind and placebo-controlled while the remainder of the study will be open-label and uncontrolled. Subjects must enroll no later than 6 weeks following completion of the parent-study.

Description:

At the first visit (Day 1), all subjects will complete Patient Acceptable Symptom State (PASS) and pain Numeric Rating Scale (NRS) assessments and then receive a blinded study injection into their target knee (the same target knee injected in the parent study), with subjects receiving the same treatment (either 0.07 mg LOR or placebo) as they received in the parent study. Subjects will have clinic visits for pain and function assessments, collection of adverse events, and knee radiographs. At Week 48, all subjects, regardless of previous treatment, will receive an injection of 0.07 mg LOR into their target knee. Subjects will receive injections of 0.07 mg LOR into their target knee every 52 weeks thereafter until end of study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 276
• Est. completion date: June 30, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 41 Years to 81 Years

Eligibility

Inclusion Criteria:

1. Completion of the Samumed study SM04690-OA-11

2. Compliance with procedures in study SM04690-OA-11, in the opinion of the Investigator

3. Fully understanding study requirements and willingness to comply with study visits and assessments

4. Understanding and signing of the informed consent form (ICF) prior to any study-related procedures

Exclusion Criteria:

1. 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

2. Any contraindications for an intra-articular (IA) injection in the target knee in the opinion of the Investigator

3. 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)

4. 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

5. Current or pending disability claim, workers' compensation, or litigation(s) that may compromise response to treatment

6. 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)

7. 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

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Placebo
Healthcare professional-administered intra-articular injection of vehicle.
• Lorecivivint
Healthcare professional-administered intra-articular injections of lorecivivint.

Locations

Country	Name	City	State
United States	Research Site	Anaheim	California
United States	Research Site	Bay City	Michigan
United States	Research Site	Carrollton	Texas
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Denver	Colorado
United States	Research Site	Draper	Utah
United States	Research Site	Fort Mill	South Carolina
United States	Research Site	Gurnee	Illinois
United States	Research Site	Hartsdale	New York
United States	Research Site	Hazelwood	Missouri
United States	Research Site	Hialeah	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami Lakes	Florida
United States	Research Site	Mount Pleasant	South Carolina
United States	Research Site	New Orleans	Louisiana
United States	Research Site	New York	New York
United States	Research Site	Newnan	Georgia
United States	Research Site	Oak Brook	Illinois
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Omaha	Nebraska
United States	Research Site	Plano	Texas
United States	Research Site	Pomona	California
United States	Research Site	Port Orange	Florida
United States	Research Site	Rapid City	South Dakota
United States	Research Site	Rochester	New York
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Salisbury	North Carolina
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	Thousand Oaks	California
United States	Research Site	Troy	Michigan
United States	Research Site	Tucson	Arizona
United States	Research Site	Valparaiso	Indiana
United States	Research Site	West Palm Beach	Florida
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Winter Haven	Florida
United States	Research Site	Winter Park	Florida
United States	Research Site	Woodstock	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Biosplice Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Safety Outcome: Number of participants with adverse events (AEs) and serious adverse events (SAEs)	AEs that occur during the study will be recorded, and ongoing AEs at the end of the parent-study will continue to be monitored. All AEs will be evaluated for severity, seriousness and causal relationship to study medication.	Visit 1E (Day 1) through Visit 3E (Week 48)
Primary	Primary Efficacy Outcome: Change from parent-study baseline medial joint space width (mJSW) in the target knee	Change from parent-study baseline in mJSW as documented by radiograph (X-ray) of the target knee	Parent-study baseline; Visit 3E (Week 48)
Secondary	Change from parent-study baseline OA pain in the target knee	Change from parent-study 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.	Parent-study baseline; Visit 2E (Week 24)
Secondary	Change from parent-study baseline OA function in the target knee	Change from parent-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 to 170.	Parent-study baseline; Visit 2E (Week 24)
Secondary	Change from parent-study baseline OA pain in the target knee	Change from parent-study 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.	Parent-study baseline; Visit 3E (Week 48)
Secondary	Change from parent-study baseline OA function in the target knee	Change from parent-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 to 170.	Parent-study baseline; Visit 3E (Week 48)