A Study Utilizing Patient-Reported Outcomes to Evaluate the Safety and Efficacy of Lorecivivint (SM04690) for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis

Knee Osteoarthritis Clinical Trial

— STRIDES-1  

Official title:

A Phase 3, 28-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of a Single Injection of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04385303
• Other study ID #: SM04690-OA-10
• Status: Completed
• Phase: Phase 3
• Start date: May 26, 2020
• Est. completion date: September 8, 2021

Study information

• Verified date: March 2022
• Source: Biosplice Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 498
• Est. completion date: September 8, 2021
• Est. primary completion date: September 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Key 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

Key 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

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Lorecivivint
One intra-articular injection of 0.07 mg lorecivivint in 2 m vehicle
• Placebo
One intra-articular injection of 0 mg lorecivivint in 2 m vehicle

Locations

Country	Name	City	State
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Anaheim	California
United States	Research Site	Bellaire	Texas
United States	Research Site	Beverly Hills	California
United States	Research Site	Birmingham	Alabama
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boise	Idaho
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boulder	Colorado
United States	Research Site	Canoga Park	California
United States	Research Site	Carrollton	Texas
United States	Research Site	Charleston	South Carolina
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Reserach Site	Clearwater	Florida
United States	Research Site	Dallas	Texas
United States	Research Site	Draper	Utah
United States	Research Site	Duncansville	Pennsylvania
United States	Research Site	Edgewater	Florida
United States	Research Site	Edmond	Oklahoma
United States	Research Site	Evansville	Indiana
United States	Research Site	Fort Mill	South Carolina
United States	Research Site	Freehold	New Jersey
United States	Research Site	Garden Grove	California
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Greenwood	Indiana
United States	Research Site	Gulf Breeze	Florida
United States	Research Site	Gurnee	Illinois
United States	Research Site	Hamden	Connecticut
United States	Research Site	Hartsdale	New York
United States	Research Site	Hazelwood	Missouri
United States	Research Site	Houston	Texas
United States	Research Site	Kansas City	Missouri
United States	Research Site	La Mesa	California
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Marietta	Georgia
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami Lakes	Florida
United States	Research Site	Mobile	Alabama
United States	Research Site	Mount Pleasant	South Carolina
United States	Research Site	New Orleans	Louisiana
United States	Research Site	Newnan	Georgia
United States	Research Site	Norco	California
United States	Research Site	Oak Brook	Illinois
United States	Research Site	Ogden	Utah
United States	Research Site	Omaha	Nebraska
United States	Research Site	Phoenix	Arizona
United States	Research Site	Phoenix	Arizona
United States	Research Site	Plano	Texas
United States	Research Site	Pomona	California
United States	Research Site	Rapid City	South Dakota
United States	Research Site	Reno	Nevada
United States	Research Site	Richmond	Virginia
United States	Research Site	Rochester	New York
United States	Research Site 1	Saint Louis	Missouri
United States	Research Site 2	Saint Louis	Missouri
United States	Research Site	Salisbury	North Carolina
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Diego	California
United States	Research Site	Santa Monica	California
United States	Research Site	Sunrise	Florida
United States	Research Site	Sweetwater	Florida
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	Westminster	California
United States	Research Site	Wheaton	Maryland
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Winter Haven	Florida
United States	Research Site 1	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	Change from baseline OA pain in the target knee as assessed by the weekly average of daily pain numeric rating scale (NRS) at Week 12	Evaluate change from baseline OA pain in the target knee as assessed by the weekly average of daily pain NRS at Week 12. 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	Change from baseline OA pain in the target knee as assessed by the weekly average of daily pain numeric rating scale (NRS) at Week 24	Evaluate change from baseline OA pain in the target knee as assessed by the weekly average of daily pain NRS at Week 24. 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 24
Secondary	Change from baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function subscore (WOMAC Function) at Weeks 12 and 24	Evaluate change from baseline OA function in the target knee as assessed by WOMAC Function subscore at Weeks 12 and 24. The WOMAC is a widely-used, proprietary outcome measurement tool used 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 4 (highest pain/highest stiffness/lowest function). The WOMAC Function subscore ranges from 0 to 68.	Baseline, Weeks 12 and 24
Secondary	Change from baseline OA disease activity as assessed by Patient Global Assessment at Weeks 12 and 24	Evaluate change from baseline OA disease activity as assessed by Patient Global Assessment at Weeks 12 and 24. The Patient Global Assessment is an 11-point [0-10] Numeric Rating Scale [NRS] on which the subjects will rate how they feel their target knee OA is doing, considering all the ways in which their target knee OA may affect them. The NRS is anchored by descriptors at each end ("Very Good" on the left and "Very Bad" on the right).	Baseline, Weeks 12 and 24
Secondary	Change from baseline in usage of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen for target knee OA pain at Week 24	Evaluate change from baseline in usage of NSAIDs and acetaminophen for target knee OA pain at Week 24.	Baseline, Week 24