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

Knee Osteoarthritis Clinical Trial

— STRIDES-X-ray  

Official title:

A Phase 3, 56-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Utilizing Patient-Reported and Radiographic Outcomes 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: NCT03928184
• Other study ID #: SM04690-OA-11
• Status: Completed
• Phase: Phase 3
• Start date: May 17, 2019
• Est. completion date: August 20, 2021

Study information

• Verified date: October 2021
• 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 intra-articularly (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 radiographs and patient reported outcomes (PROs) to evaluate the safety and efficacy of lorecivivint.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 513
• Est. completion date: August 20, 2021
• Est. primary completion date: August 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Males and females between 40 and 80 years of age, inclusive, in general good health apart from their knee OA

2. Ambulatory (single assistive devices such as canes allowed if needed less than 50% of the time, subjects requiring a walker are excluded)

3. 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)

4. mJSW by radiograph between 1.5 and 4 mm, inclusive, in the target knee within 12 weeks of the Screening Visit as assessed by independent central readers

5. Radiographic disease Stage 2 or 3 in the target knee within 12 weeks of the Screening Visit according to the Kellgren-Lawrence (KL) grading of knee OA as assessed by independent central readers

6. Pain compatible with OA of the knee(s) for at least 26 weeks prior to the Screening Visit

7. Primary source of pain throughout the body is due to OA in the target knee

8. Body mass index (BMI) = 40 kg/m2 at the Screening Visit

9. Widespread Pain Index (WPI) score of = 4 and a Symptom Severity Question 2 (SSQ2) score of = 2 at the Screening Visit and Day 1

10. Pain NRS scores recorded for the target knee on at least 4 out of the 7 days immediately preceding Day 1

11. Pain NRS scores recorded for the nontarget knee on at least 4 out of the 7 days immediately preceding Day 1

12. Daily OA knee pain diary average 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

13. Daily OA knee pain diary average NRS intensity score < 4 in the nontarget knee on the 11-point (0-10) NRS scale for the 7 days immediately preceding Day 1

14. WOMAC Pain of 20-40 (out of 50) for the target knee at baseline regardless of if the subject is on symptomatic oral treatment (baseline questionnaire completed during the screening period prior to randomization)

15. WOMAC Function of 68-136 (out of 170) for the target knee at baseline regardless of if the subject is on symptomatic oral treatment (baseline questionnaire completed during the screening period prior to randomization)

16. Willingness to use an electronic diary daily in the evening for the screening period and 56-week study duration

17. 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

18. Subjects with depression or anxiety must be clinically stable for at least 12 weeks prior to the Screening Visit and, if on treatment for depression or anxiety, be on at least 12 weeks of stable therapy

19. Full understanding of the requirements of the study and willingness to comply with all study visits and assessments

20. Subjects must have read and understood the informed consent form (ICF), and must have signed and dated it prior to any study-related procedure being performed

Exclusion Criteria:

1. Pregnant women, breastfeeding woman, 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

2. Women who are not post-menopausal or permanently surgically sterile who are sexually active, and who are not willing to use birth control during the study period

3. Men who are sexually active and of reproductive potential, who have partners who are capable of becoming pregnant, and who are not willing to use birth control during the study period

4. Significant malalignment of anatomical axis (medial angle formed by the femur and tibia) of the target knee (varus > 10°, valgus > 10°) by radiograph within 12 weeks of the Screening Visit as assessed by independent central readers

5. Partial or complete joint replacement in either knee

6. Currently requires use of a lower extremity prosthesis, and/or a structural knee brace (i.e., a knee brace that contains hardware)

7. Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to Day 1

8. 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

9. Effusion of the target knee clinically requiring aspiration within 12 weeks prior to Day 1

10. Use of electrotherapy, acupuncture, physical therapy, therapeutic ultrasound, and/or chiropractic treatments for knee OA within 4 weeks prior to Day 1

11. Any bone fracture(s) within 26 weeks prior to the Screening Visit

12. Previous treatment with SM04690

13. Subjects who have previously failed screening on this protocol and fail to meet rescreening criteria

14. Participation in a clinical research trial that included the receipt of an investigational product (IP) or any experimental therapeutic procedure within 26 weeks prior to the Screening Visit, or planned participation in any such trial

15. Treatment with systemic (oral, intramuscular, or intravenous) glucocorticoids =10 mg prednisone or the equivalent per day within 4 weeks prior to Day 1, or subjects on <10 mg prednisone or the equivalent per day who have not maintained a stable regimen for at least 2 weeks prior to Day 1 in the opinion of the Investigator

16. Use of centrally acting analgesics within 12 weeks prior to Day 1

17. Use of anticonvulsants within 12 weeks prior to Day 1

18. Subjects requiring the use of opioids > 1x per week within 12 weeks prior to Day 1

19. Topical local anesthetic agents (gels, creams, or patches such as the Lidoderm patch) used for the treatment of knee OA within 7 days of Day 1

20. Planned surgery scheduled during the study period, not including non-surgical invasive procedures conducted for a diagnostic or therapeutic purpose scheduled during the study period

21. 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

22. Clinically significant abnormal screening hematology values, blood chemistry values, or urinalysis values as determined by the Investigator

23. 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

24. Other conditions that, in the opinion of the Investigator, could affect study endpoint assessments of either knee, including, but not limited to, peripheral neuropathy (e.g., diabetic neuropathy), symptomatic hip osteoarthritis, symptomatic degenerative disc disease, and patellofemoral syndrome

25. Comorbid conditions that could affect study endpoint assessments of the target knee, including, but not limited to, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, gout or pseudogout, and fibromyalgia

26. History of mania, bipolar disorder, psychotic disorder, schizophrenia, or schizoaffective disorder

27. 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

28. Any chronic condition that has not been well controlled or subjects with a chronic condition who have not maintained a stable therapeutic regimen of a prescription therapy in the opinion of the Investigator.

29. Hemoglobin A1c (HbA1c) >9 at the Screening Visit

30. If using NSAIDs and/or acetaminophen, subjects who have not maintained a stable regimen in the opinion of the Investigator for at least 4 weeks prior to Day 1

31. Any contraindications for an IA injection in the target knee in the opinion of the Investigator

32. Subjects who have a current or pending disability claim, workers' compensation, or litigation(s) that may compromise response to treatment

33. Subjects who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at any investigative site, or are directly affiliated with the study at any investigative site

34. Subjects employed by Samumed, LLC, or any of its affiliates or development partners (that is, an employee, temporary contract worker, or designee) responsible for the conduct of the study, or who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of said employees responsible for the conduct of the study

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Lorecivivint
Healthcare professional-administered intra-articular injection; performed on Day 1
• Placebo
Healthcare professional-administered intra-articular injection; performed on Day 1

Locations

Country	Name	City	State
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Anaheim	California
United States	Research Site	Anderson	Indiana
United States	Research Site	Austin	Texas
United States	Research Site	Bay City	Michigan
United States	Research Site	Bedford	Texas
United States	Research Site	Birmingham	Alabama
United States	Research Site	Birmingham	Alabama
United States	Research Site	Birmingham	Alabama
United States	Research Site	Bloomington	Illinois
United States	Research Site	Boise	Idaho
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boulder	Colorado
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	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Clearwater	Florida
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Columbus	Ohio
United States	Research Site	Coral Gables	Florida
United States	Research Site	Dallas	Texas
United States	Research Site	Denver	Colorado
United States	Research Site	Draper	Utah
United States	Research Site	Duncansville	Pennsylvania
United States	Research Site	Edinburg	Texas
United States	Research Site	Evansville	Indiana
United States	Research Site	Fargo	North Dakota
United States	Research Site	Fort Mill	South Carolina
United States	Research Site	Garden Grove	California
United States	Research Site	Great Neck	New York
United States	Research Site	Greenville	South Carolina
United States	Research Site	Greer	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	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Kansas City	Kansas
United States	Research Site	La Vista	Nebraska
United States	Research Site	Leland	North Carolina
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Marietta	Georgia
United States	Research Site	Meridian	Idaho
United States	Research Site	Miami	Florida
United States	Research Site	Miami Lakes	Florida
United States	Research Site	Monroe	Louisiana
United States	Research Site	Mount Pleasant	South Carolina
United States	Research Site	Murray	Utah
United States	Research Site	New Orleans	Louisiana
United States	Research Site	New York	New York
United States	Research Site 1	New York	New York
United States	Research Site 2	New York	New York
United States	Research Site	Newnan	Georgia
United States	Research Site	Norco	California
United States	Research Site	Oak Brook	Illinois
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Omaha	Nebraska
United States	Research Site	Orlando	Florida
United States	Research Site	Oviedo	Florida
United States	Research Site	Peoria	Arizona
United States	Research Site	Phoenix	Arizona
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	Richmond	Virginia
United States	Research Site	Rochester	New York
United States	Research Site	Rockford	Illinois
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 Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	San Marcos	California
United States	Research Site	Spring Valley	California
United States	Research Site	Stockbridge	Georgia
United States	Research Site	Sunrise	Florida
United States	Research Site	Troy	Michigan
United States	Research Site	Tucson	Arizona
United States	Research Site	Valparaiso	Indiana
United States	Research Site	Waterbury	Connecticut
United States	Research Site	West Palm Beach	Florida
United States	Research Site	Westminster	California
United States	Research Site	Wheaton	Maryland
United States	Research Site	Wichita	Kansas
United States	Research Site	Williamsville	New York
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 #2	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
Other	Change from baseline in serum bone biomarkers	Evaluate change from baseline in serum bone biomarkers N-terminal propeptides of procollagen type I [PINP] and ß-C-terminal telopeptide [ß-CTX]	Baseline and Week 56
Other	Change from baseline in a serum cartilage biomarker	Evaluate change from baseline in serum cartilage biomarker cartilage oligomeric matrix protein [COMP]	Baseline and Week 56
Other	Change from baseline in medial joint space width (mJSW) in the target knee	Evaluate change from baseline in mJSW as documented by radiograph of the target knee	Baseline and Week 52
Other	Change from baseline in health-related quality of life (HRQOL)	Evaluate change from baseline in HRQOL as assessed by the 36-Item Short Form Health Survey (SF-36). The SF-36 consists of eight scaled scores which are the weighted sums of the questions in their section (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health). Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. A score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.	Baseline and Week 52
Other	Change from baseline in OA pain in the target knee (WOMAC Pain)	Evaluate change from baseline in OA pain in the target knee as assessed by WOMAC pain subscore (WOMAC Pain). 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 Pain subscore ranges from 0 to 20.	Baseline, Weeks 12, 24 and 52
Other	Change from baseline in OA pain, function and stiffness (WOMAC Total score)	Evaluate change from baseline in OA pain, function and stiffness as a composite outcome measure as assessed by WOMAC Total score. 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). WOMAC Total is a composite of the three domains (pain/stiffness/function) with a total score of 0 to 96.	Baseline, Weeks 12, 24 and 52
Primary	Change from baseline in OA pain in the target knee (pain NRS)	Evaluate change from 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.	Baseline and Week 12
Secondary	Change from baseline in OA pain in the target knee (Pain NRS)	Evaluate change from 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.	Baseline, Weeks 24 and 52
Secondary	Change from baseline in OA function in the target knee (WOMAC Function)	Evaluate 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). 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, 24 and 52
Secondary	Change from baseline in OA disease activity (Patient Global Assessment)	Evaluate change from baseline OA disease activity as assessed by Patient Global Assessment. 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, 24 and 52
Secondary	Change from baseline in usage of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen for target knee OA pain		Baseline and Week 52