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

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

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.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: Placebo; Drug: SM04690

• Study Type: Interventional
• Enrollment (Actual): 455
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Research Site
  • Arizona
    • Phoenix, Arizona, United States, 85029
      • Research Site
    • Tucson, Arizona, United States, 85712
      • Research Site
  • California
    • El Cajon, California, United States, 92020
      • Research Site
    • Rancho Mirage, California, United States, 92270
      • Research Site
    • Spring Valley, California, United States, 91978
      • Research Site
  • Colorado
    • Denver, Colorado, United States, 80230
      • Research Site
  • Florida
    • Clearwater, Florida, United States, 33761
      • Research Site
    • Coral Gables, Florida, United States, 33134
      • Research Site
    • Jacksonville, Florida, United States, 32216
      • Research Site
    • Miami, Florida, United States, 33173
      • Research Site
    • West Palm Beach, Florida, United States, 33409
      • Research Site
  • Georgia
    • Woodstock, Georgia, United States, 30189
      • Research Site
  • Kansas
    • Newton, Kansas, United States, 67114
      • Research Site
    • Wichita, Kansas, United States, 67205
      • Research Site
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Research Site
  • Maryland
    • Frederick, Maryland, United States, 21702
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Research Site
    • Worcester, Massachusetts, United States, 01605
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Research Site 1
    • Saint Louis, Missouri, United States, 63141
      • Research Site 2
  • New York
    • Orchard Park, New York, United States, 14127
      • Research Site
    • Rochester, New York, United States, 14609
      • Research Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Research Site
    • Salisbury, North Carolina, United States, 28144
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45246
      • Research Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Research Site
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Research Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Research Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37912
      • Research Site
  • Texas
    • Austin, Texas, United States, 78745
      • Research Site
    • Houston, Texas, United States, 77074
      • Research Site
  • Utah
    • West Layton, Utah, United States, 84041
      • Research Site
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Research Site
    • Richmond, Virginia, United States, 23225
      • Research Site
  • Wisconsin
    • Franklin, Wisconsin, United States, 53132
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.03 mg SM04690; Single intra-articular injection of SM04690 0.03 mg in 2 mL injectable suspension	Drug: SM04690
Experimental: 0.07 mg SM04690; Single intra-articular injection of SM04690 0.07 mg in 2 mL injectable suspension	Drug: SM04690
Experimental: 0.23 mg SM04690; Single intra-articular injection of SM04690 0.23 mg in 2 mL injectable suspension	Drug: SM04690
Placebo Comparator: Placebo; Single intra-articular injection of SM04690 0 mg in 2 mL phosphate buffered saline	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline Osteoarthritis (OA) Pain in the Target Knee	Change from baseline OA pain in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain) at Week 13. 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 Pain subscore is reported ranging from 0 to 100.	Baseline and Week 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline OA Pain in the Target Knee	Change from baseline OA pain in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain) at Week 26. 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 Pain subscore is reported ranging from 0 to 100.	Baseline and Week 26
Change From Baseline OA Function in the Target Knee	Change from 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) at Week 13. 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 is reported ranging from 0 to 100.	Baseline and Week 13
Change From Baseline OA Function in the Target Knee	Change from 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) at Week 26. 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 is reported ranging from 0 to 100.	Baseline and Week 26
Change From Baseline OA Disease Activity as Assessed by the Patient	Change from baseline OA disease activity as assessed by the Patient Global Assessment at Week 13. The Patient Global Assessment was completed using a 100 mm visual analog scale (VAS) adapted from the Patient Assessment Form © 1999, American College of Rheumatology. The subject rated how well he/she was doing, considering all the ways in which illness and health conditions may affected him/her. The VAS scale was anchored by "Very Well" on the left (scored as 0) and "Very Poorly" on the right (scored as 100). Higher scores indicated poorer disease assessment by the subject.	Baseline and Week 13
Change From Baseline OA Disease Activity as Assessed by the Patient	Change from baseline OA disease activity as assessed by the Patient Global Assessment at Week 26. The Patient Global Assessment was completed using a 100 mm visual analog scale (VAS) adapted from the Patient Assessment Form © 1999, American College of Rheumatology. The subject rated how well he/she was doing, considering all the ways in which illness and health conditions may affected him/her. The VAS scale was anchored by "Very Well" on the left (scored as 0) and "Very Poorly" on the right (scored as 100). Higher scores indicated poorer disease assessment by the subject.	Baseline and Week 26
Change From Baseline in Medial Joint Space Width of Target Knee	Change from baseline in medial joint space width as documented by X-ray of the target knee at Week 26.	Baseline and Week 26

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline OA Pain in the Target Knee	Change from baseline OA pain in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain) at Week 52. 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 Pain subscore is reported ranging from 0 to 100.	Baseline and Week 52
Change From Baseline OA Function in the Target Knee	Change from 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) at Week 52. 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 is reported ranging from 0 to 100.	Baseline and Week 52
Change From Baseline in Medial Joint Space Width of Target Knee	Change from baseline in medial joint space width as documented by X-ray of the target knee at Week 52.	Baseline and Week 52
Change From Baseline OA Pain in the Target Knee [Unilateral Symptomatic OA]	Change from baseline OA pain in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain) at Week 52. 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 Pain subscore is reported ranging from 0 to 100.	Baseline and Week 52
Change From Baseline OA Function in the Target Knee [Unilateral Symptomatic OA]	Change from 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) at Week 52. 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 is reported ranging from 0 to 100.	Baseline and Week 52
Change From Baseline in Medial Joint Space Width of Target Knee [Unilateral Symptomatic OA]	Change from baseline in medial joint space width as documented by X-ray of the target knee at Week 52.	Baseline and Week 52

Collaborators and Investigators

• Sponsor: Biosplice Therapeutics, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2015
• Primary Completion (Actual): April 20, 2017
• Study Completion (Actual): April 20, 2017

Study Registration Dates

• First Submitted: August 28, 2015
• First Submitted That Met QC Criteria: August 28, 2015
• First Posted (Estimate): September 1, 2015

Study Record Updates

• Last Update Posted (Actual): March 17, 2021
• Last Update Submitted That Met QC Criteria: March 15, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Osteoarthritis; Samumed; SM04690
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Anti-Inflammatory Agents; Lorecivivint
• Other Study ID Numbers: SM04690-OA-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No