A Study Evaluating the Safety, Tolerability, and Efficacy of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects

NCT ID: NCT02536833

Last Updated: 2021-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 455 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-09
• Study Completion Date: 2017-04-20

Brief Summary

The purpose of this study is to assess the efficacy, safety, and tolerability of three different strengths of SM04690 injected in the target knee joint of moderately to severely symptomatic osteoarthritis (OA) subjects.

Conditions

Osteoarthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

0.03 mg SM04690

Single intra-articular injection of SM04690 0.03 mg in 2 mL injectable suspension

Group Type: EXPERIMENTAL

SM04690

Intervention Type: DRUG

0.07 mg SM04690

Single intra-articular injection of SM04690 0.07 mg in 2 mL injectable suspension

Group Type: EXPERIMENTAL

SM04690

Intervention Type: DRUG

0.23 mg SM04690

Single intra-articular injection of SM04690 0.23 mg in 2 mL injectable suspension

Group Type: EXPERIMENTAL

SM04690

Intervention Type: DRUG

Placebo

Single intra-articular injection of SM04690 0 mg in 2 mL phosphate buffered saline

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

SM04690

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Males and females between 40 and 80 years of age, inclusive, in general good health

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

3. Established diagnosis of primary femorotibial OA in the target knee by standard American College of Rheumatology (ACR) criteria for at least 6 months (clinical AND radiographic criteria); if bilateral knee OA is present, the target knee is defined as the knee with greater pain at screening based on the subject's evaluation and the Investigator's clinical judgment

4. Radiographic disease Stage 2 or 3 in the target knee according to the Kellgren-Lawrence grading of knee OA as assessed by independent central readers

5. Screening pain visual analog scale (VAS) score of 30-80 mm (on a scale of 0-100 mm) for the target knee while on symptomatic oral treatment at screening (if the subject requires oral treatment)

6. Total WOMAC score of 72-192 (out of 240) for the target knee while on symptomatic oral treatment at screening (if the subject requires oral treatment)

7. Willingness to omit the following for 24 hours prior to all Study Visits, excluding the Screening Visit:

1. Pain medications

2. Medications or supplements for the treatment of OA

3. Participation in a formalized in-office and/or supervised OA disease program (e.g., a prescribed patient education program, physiotherapy, etc.)

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

9. Subjects must have read and understood the informed consent form, and must have signed it prior to any study-related procedure being performed

10. Subject's Day 1 visit must occur while enrollment into the study is open

Exclusion Criteria

1. Women who are pregnant or lactating

2. Women of childbearing potential (i.e., who are not surgically sterile or postmenopausal as defined by no menstrual periods for 12 consecutive months and no other biological or physiological cause for amenorrhea can be identified); males who are sexually active and have a partner who is capable of becoming pregnant, neither of which have had surgery to become sterilized, who are not using an effective method of birth control (e.g., surgically-implanted hormonal therapy, intrauterine devices or oral birth control with barrier method)

3. Body mass index (BMI) >40

4. Partial or complete joint replacement in the target knee

5. Previous exposure to SM04690

6. Major surgery (e.g., interventional arthroscopy) in the target knee within 52 weeks prior to any study injection

7. Any planned or elective surgery during the study period

8. Significant and clinically evident misalignment of the target knee that would impact subject function, as determined by the Investigator

9. History of malignancy within the last 5 years; however, subjects with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they have been continuously disease free for at least 5 years prior to any study injection

10. Clinically significant abnormal Screening Visit hematology values, blood chemistry values, HbA1c, or urinalysis values as determined by the investigator

11. 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

12. Comorbid conditions that could affect pain assessment of the target knee, including, but not limited to, inflammatory rheumatic conditions such as rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, diabetic neuropathy, pseudogout, gout, and fibromyalgia

13. Other conditions that, in the opinion of the Investigator, could affect pain assessment of the target knee, including, but not limited to, symptomatic hip osteoarthritis and symptomatic degenerative disc disease

14. Any diagnosed psychiatric condition that includes, but is not limited to, a history of mania, bipolar disorder, psychotic disorder, schizophrenia, major depressive disorder, or generalized anxiety disorder

15. Participation in a clinical research trial that included the receipt of an investigational product or any experimental therapeutic procedure within 12 weeks prior to any study injection; the last date of participation in the trial, not the last date of receipt of investigational product, must be at least 12 weeks prior to Study Visit Day 1

16. Treatment of the target knee with systemic or intra-articular corticosteroids (e.g., methylprednisolone) within 8 weeks prior to Study Visit Day 1

17. Viscosupplementation (e.g., hyaluronic acid) in the target knee within 24 weeks prior to Study Visit Day 1

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

19. Use of electrotherapy, acupuncture, and/or chiropractic treatments for knee OA within 4 weeks prior to Study Visit Day 1

20. Any known active infections, including suspicion of intra-articular infection, hepatitis B or hepatitis C infection, and/or infections that may compromise the immune system such as human immunodeficiency virus (HIV)

21. Subjects taking prescription medications for OA who have not maintained a stable therapeutic regimen for a minimum of 12 weeks prior to Study Visit Day 1

22. Subjects requiring the chronic use (i.e., regular and consistent use for ≥ 12 weeks) of the medications listed below within 12 weeks prior to Study Visit Day 1:

1. Opioids, both oral (e.g., tramadol) or transdermal (e.g., fentanyl patches) formulations

2. Centrally acting analgesics (e.g., duloxetine)

3. Glucocorticoids (e.g., methylprednisolone) administered by any route, with exception of inhaled, intranasal, and ophthalmic solutions

23. 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 for a minimum of 12 weeks prior to Study Visit Day 1. In addition, the following subjects will be excluded:

1. Subjects with a baseline HbA1c >9

2. Subjects with uncontrolled hypertension in the opinion of the investigator

3. Subjects with symptomatic coronary artery disease in the opinion of the investigator

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

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

26. 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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biosplice Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yusuf Yazici, M.D.

Role: STUDY_DIRECTOR

Biosplice Therapeutics, Inc.

Locations

Research Site

Mobile, Alabama, United States

Research Site

Phoenix, Arizona, United States

Research Site

Tucson, Arizona, United States

Research Site

El Cajon, California, United States

Research Site

Rancho Mirage, California, United States

Research Site

Spring Valley, California, United States

Research Site

Denver, Colorado, United States

Research Site

Clearwater, Florida, United States

Research Site

Coral Gables, Florida, United States

Research Site

Jacksonville, Florida, United States

Research Site

Miami, Florida, United States

Research Site

West Palm Beach, Florida, United States

Research Site

Woodstock, Georgia, United States

Research Site

Newton, Kansas, United States

Research Site

Wichita, Kansas, United States

Research Site

Lexington, Kentucky, United States

Research Site

Frederick, Maryland, United States

Research Site

Boston, Massachusetts, United States

Research Site

Worcester, Massachusetts, United States

Research Site 1

St Louis, Missouri, United States

Research Site 2

St Louis, Missouri, United States

Research Site

Orchard Park, New York, United States

Research Site

Rochester, New York, United States

Research Site

Raleigh, North Carolina, United States

Research Site

Salisbury, North Carolina, United States

Research Site

Cincinnati, Ohio, United States

Research Site

Duncansville, Pennsylvania, United States

Research Site

Mt. Pleasant, South Carolina, United States

Research Site

Rapid City, South Dakota, United States

Research Site

Knoxville, Tennessee, United States

Research Site

Austin, Texas, United States

Research Site

Houston, Texas, United States

Research Site

West Layton, Utah, United States

Research Site

Charlottesville, Virginia, United States

Research Site

Richmond, Virginia, United States

Research Site

Franklin, Wisconsin, United States

Countries

United States

References

Yazici Y, McAlindon TE, Gibofsky A, Lane NE, Clauw D, Jones M, Bergfeld J, Swearingen CJ, DiFrancesco A, Simsek I, Tambiah J, Hochberg MC. Lorecivivint, a Novel Intraarticular CDC-like Kinase 2 and Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A Inhibitor and Wnt Pathway Modulator for the Treatment of Knee Osteoarthritis: A Phase II Randomized Trial. Arthritis Rheumatol. 2020 Oct;72(10):1694-1706. doi: 10.1002/art.41315. Epub 2020 Sep 6.

Reference Type: RESULT

PMID: 32432388 (View on PubMed)

Tambiah J, Kennedy S, Swearingen C, McAlindon T, Yazici Y. Impact of structural severity on outcomes in knee osteoarthritis: an analysis of data from phase 2 and phase 3 lorecivivint clinical trials. Rheumatology (Oxford). 2025 May 1;64(5):2583-2590. doi: 10.1093/rheumatology/keae610.

Reference Type: DERIVED

PMID: 39495154 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SM04690-OA-02

Identifier Type: -

Identifier Source: org_study_id