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

NCT02536833 | Completed Phase 2 Results FDA Drug

• 1 other identifier: SM04690-OA-02
• Study Type: interventional
• Target: 455
• Locations: 1 country
• Sites: 36

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

Keywords

Osteoarthritis; Samumed; SM04690

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Change From Baseline OA Pain in the Target Knee

  Baseline and Week 26

• Change From Baseline OA Function in the Target Knee

  Baseline and Week 13

• Change From Baseline OA Function in the Target Knee

  Baseline and Week 26

• Change From Baseline OA Disease Activity as Assessed by the Patient

  Baseline and Week 13

• Change From Baseline OA Disease Activity as Assessed by the Patient

  Baseline and Week 26

Other Outcomes (6)

• Change From Baseline OA Pain in the Target Knee

  Baseline and Week 52

• Change From Baseline OA Function in the Target Knee

  Baseline and Week 52

• Change From Baseline in Medial Joint Space Width of Target Knee

  Baseline and Week 52

Study Arms (4)

0.03 mg SM04690

EXPERIMENTAL

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

Drug: SM04690

0.07 mg SM04690

EXPERIMENTAL

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

Drug: SM04690

0.23 mg SM04690

EXPERIMENTAL

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

Drug: SM04690

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

SM04690 DRUG

0.03 mg SM04690; 0.07 mg SM04690; 0.23 mg SM04690

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females between 40 and 80 years of age, inclusive, in general good health
• Ambulatory (single assistive devices such as canes allowed if needed less than 50% of the time, subjects requiring a walker are excluded)
• 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
• 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
• 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)
• 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)
• Willingness to omit the following for 24 hours prior to all Study Visits, excluding the Screening Visit:
• Pain medications
• Medications or supplements for the treatment of OA
• Participation in a formalized in-office and/or supervised OA disease program (e.g., a prescribed patient education program, physiotherapy, etc.)
• Full understanding of the requirements of the study and willingness to comply with all study visits and assessments
• Subjects must have read and understood the informed consent form, and must have signed it prior to any study-related procedure being performed
• Subject's Day 1 visit must occur while enrollment into the study is open

You may not qualify if:

• Women who are pregnant or lactating
• 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)
• Body mass index (BMI) \>40
• Partial or complete joint replacement in the target knee
• Previous exposure to SM04690
• Major surgery (e.g., interventional arthroscopy) in the target knee within 52 weeks prior to any study injection
• Any planned or elective surgery during the study period
• Significant and clinically evident misalignment of the target knee that would impact subject function, as determined by the Investigator
• 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
• Clinically significant abnormal Screening Visit hematology values, blood chemistry values, HbA1c, or urinalysis values as determined by the investigator
• 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
• 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
• 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
• 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
• 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

Sponsors & Collaborators

• Biosplice Therapeutics, Inc.: lead

Study Sites (36)

Research Site

Mobile, Alabama, 36608, United States

Location

Research Site

Phoenix, Arizona, 85029, United States

Location

Research Site

Tucson, Arizona, 85712, United States

Location

Research Site

El Cajon, California, 92020, United States

Location

Research Site

Rancho Mirage, California, 92270, United States

Location

Research Site

Spring Valley, California, 91978, United States

Location

Research Site

Denver, Colorado, 80230, United States

Location

Research Site

Clearwater, Florida, 33761, United States

Location

Research Site

Coral Gables, Florida, 33134, United States

Location

Research Site

Jacksonville, Florida, 32216, United States

Location

Research Site

Miami, Florida, 33173, United States

Location

Research Site

West Palm Beach, Florida, 33409, United States

Location

Research Site

Woodstock, Georgia, 30189, United States

Location

Research Site

Newton, Kansas, 67114, United States

Location

Research Site

Wichita, Kansas, 67205, United States

Location

Research Site

Lexington, Kentucky, 40504, United States

Location

Research Site

Frederick, Maryland, 21702, United States

Location

Research Site

Boston, Massachusetts, 02111, United States

Location

Research Site

Worcester, Massachusetts, 01605, United States

Location

Research Site 1

St Louis, Missouri, 63141, United States

Location

Research Site 2

St Louis, Missouri, 63141, United States

Location

Research Site

Orchard Park, New York, 14127, United States

Location

Research Site

Rochester, New York, 14609, United States

Location

Research Site

Raleigh, North Carolina, 27612, United States

Location

Research Site

Salisbury, North Carolina, 28144, United States

Location

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Cincinnati, Ohio, 45246, United States

Location

Research Site

Duncansville, Pennsylvania, 16635, United States

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Research Site

Mt. Pleasant, South Carolina, 29464, United States

Location

Research Site

Rapid City, South Dakota, 57702, United States

Location

Research Site

Knoxville, Tennessee, 37912, United States

Location

Research Site

Austin, Texas, 78745, United States

Location

Research Site

Houston, Texas, 77074, United States

Location

Research Site

West Layton, Utah, 84041, United States

Location

Research Site

Charlottesville, Virginia, 22911, United States

Location

Research Site

Richmond, Virginia, 23225, United States

Location

Research Site

Franklin, Wisconsin, 53132, United States

Location

Related Publications (2)

• 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.

  PMID: 32432388 RESULT

• 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.

  PMID: 39495154 DERIVED

MeSH Terms

Conditions

Osteoarthritis

Interventions

lorecivivint

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Results Point of Contact

• Title: Christopher Swearingen, PhD, VP of Clinical Outcomes and Analytics
• Organization: Samumed

chris@samumed.com

858.926.2952

Study Officials

• Yusuf Yazici, M.D.

  Biosplice Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2015
• First Posted: September 1, 2015
• Study Start: September 9, 2015
• Primary Completion: April 20, 2017
• Study Completion: April 20, 2017
• Last Updated: March 17, 2021
• Results First Posted: September 16, 2020

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (36)