Clinical trial NCT02536833: A Study Evaluating the Safety, Tolerability, and Efficacy of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects
Official title: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis
Keywords: Osteoarthritis
Samumed
SM04690
Lead sponsor: Biosplice Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2015-09-01
Enrollment: 455
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change From Baseline Osteoarthritis (OA) Pain in the Target Knee
timeFrame: Baseline and Week 13
Secondary outcomes:
measure: Change From Baseline OA Pain in the Target Knee
timeFrame: Baseline and Week 26
measure: Change From Baseline OA Function in the Target Knee
timeFrame: Baseline and Week 13
measure: Change From Baseline OA Function in the Target Knee
timeFrame: Baseline and Week 26
measure: Change From Baseline OA Disease Activity as Assessed by the Patient
timeFrame: Baseline and Week 13
measure: Change From Baseline OA Disease Activity as Assessed by the Patient
timeFrame: Baseline and Week 26
measure: Change From Baseline in Medial Joint Space Width of Target Knee
timeFrame: Baseline and Week 26
Other outcomes:
measure: Change From Baseline OA Pain in the Target Knee
timeFrame: Baseline and Week 52
measure: Change From Baseline OA Function in the Target Knee
timeFrame: Baseline and Week 52
measure: Change From Baseline in Medial Joint Space Width of Target Knee
timeFrame: Baseline and Week 52
measure: Change From Baseline OA Pain in the Target Knee [Unilateral Symptomatic OA]
timeFrame: Baseline and Week 52
measure: Change From Baseline OA Function in the Target Knee [Unilateral Symptomatic OA]
timeFrame: Baseline and Week 52
measure: Change From Baseline in Medial Joint Space Width of Target Knee [Unilateral Symptomatic OA]
timeFrame: Baseline and Week 52
Locations:
city: Mobile
country: United States
facility: Research Site
state: Alabama
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: El Cajon
country: United States
facility: Research Site
state: California
city: Rancho Mirage
country: United States
facility: Research Site
state: California
city: Spring Valley
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Clearwater
country: United States
facility: Research Site
state: Florida
city: Coral Gables
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: West Palm Beach
country: United States
facility: Research Site
state: Florida
city: Woodstock
country: United States
facility: Research Site
state: Georgia
city: Newton
country: United States
facility: Research Site
state: Kansas
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Frederick
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Worcester
country: United States
facility: Research Site
state: Massachusetts
city: Saint Louis
country: United States
facility: Research Site 1
state: Missouri
city: Saint Louis
country: United States
facility: Research Site 2
state: Missouri
city: Orchard Park
country: United States
facility: Research Site
state: New York
city: Rochester
country: United States
facility: Research Site
state: New York
city: Raleigh
country: United States
facility: Research Site
state: North Carolina
city: Salisbury
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Duncansville
country: United States
facility: Research Site
state: Pennsylvania
city: Mount Pleasant
country: United States
facility: Research Site
state: South Carolina
city: Rapid City
country: United States
facility: Research Site
state: South Dakota
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Austin
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: West Layton
country: United States
facility: Research Site
state: Utah
city: Charlottesville
country: United States
facility: Research Site
state: Virginia
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Franklin
country: United States
facility: Research Site
state: Wisconsin
Study officials:
affiliation: Biosplice Therapeutics, Inc.
name: Yusuf Yazici, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.