A Study Evaluating the Safety and Efficacy of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis

NCT03122860 | Completed Phase 2 Results FDA Drug

• 1 other identifier: SM04690-OA-04
• Study Type: interventional
• Target: 700
• Locations: 1 country
• Sites: 74

Brief Summary

This phase 2 study is a placebo-controlled, double-blind, parallel group study of four concentrations of SM04690 (0.03, 0.07, 0.15, and 0.23 mg per 2 mL injection) injected intraarticularly (IA) into the target knee joint of subjects with moderately to severely symptomatic osteoarthritis (OA). Based on previous studies of SM04690, key phenotypes of laterality (unilateral vs bilateral) as well as chronic pain (as measured by the Widespread Pain Index) were identified as confounding variables impacting the overall assessment of both radiologic and clinical efficacy outcomes. The design of SM04690-OA-04 is based upon previous study designs while assessing strategies to combat the confounding impact of laterality and chronic pain. To evaluate the effect of IA vehicle injection on patient-reported outcomes (PRO) such as pain, stiffness, and function in OA, this study also includes one cohort that receives a 2 mL IA injection of vehicle (placebo), and one cohort that receives a sham injection (i.e., a needle stick with 0 mL vehicle injected).

Conditions

Knee Osteoarthritis

Keywords

SM04690; Wnt pathway inhibitor; osteoarthritis; Samumed

Outcome Measures

Primary Outcomes (4)

• Change From Baseline Osteoarthritis (OA) Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS)

  Change from baseline OA pain in the target knee as assessed by the weekly average of daily pain NRS at Week 24. 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 (pain as bad as one can imagine).

  Baseline and Week 24

• Change From Baseline OA Pain in the Target Knee as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain)

  Change from baseline OA pain in the target knee as assessed by WOMAC Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain) at Week 24. 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 standardized and reported ranging from 0 to 100 \[0 = no pain; 100 = pain as bad as it can be\].

  Baseline and Week 24

• Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function)

  Change from baseline OA function in the target knee as assessed by WOMAC Numeric Rating Scale (NRS 3.1) physical functioning subscore (WOMAC Function) at Week 24. 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 standardized and reported ranging from 0 to 100 \[0 = no functional disability, 100 = unable to function\].

  Baseline and Week 24

• Change From Baseline in Medial Joint Space Width (mJSW) of the Target Knee

  Change from baseline in mJSW as documented by radiograph of the target knee.

  Baseline and Week 24

Secondary Outcomes (1)

• Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA)

  Baseline and Week 24

Other Outcomes (4)

• Change From Baseline OA Pain in the Target Knee as Assessed by WOMAC Pain Subscore (WOMAC Pain)

  Baseline and Week 12

• Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function)

  Baseline and Week 12

• Change From Baseline OA Pain in the Target Knee as Assesses by the Weekly Average of Daily Pain NRS

  Baseline and Week 12

Study Arms (6)

0.03 mg SM04690

EXPERIMENTAL

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

Drug: SM04690

0.07 mg SM04690

EXPERIMENTAL

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

Drug: SM04690

0.15 mg SM04690

EXPERIMENTAL

Single intra-articular injection of 0.15 mg SM04690 in 2 mL vehicle

Drug: SM04690

0.23 mg SM04690

EXPERIMENTAL

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

Drug: SM04690

Placebo

PLACEBO COMPARATOR

Single intra-articular injection of 0 mg SM04690 in 2 mL vehicle

Other: Placebo

Sham

SHAM COMPARATOR

Single intra-articular injection of 0 mg SM04690 in 0 mL vehicle

Other: Sham

Interventions

SM04690 DRUG

Healthcare professional-administered intra-articular injection performed once on Day 1 of the study

0.03 mg SM04690; 0.07 mg SM04690; 0.15 mg SM04690; 0.23 mg SM04690

Placebo OTHER

Healthcare professional-administered intra-articular injection performed once on Day 1 of the study

Placebo

Sham OTHER

Healthcare professional-administered intra-articular injection performed once on Day 1 of the study

Sham

Eligibility Criteria

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

You may qualify if:

• Ambulatory
• Diagnosis of femorotibial OA in the target knee by standard American College of Rheumatology (ACR) criteria at screening (clinical AND radiographic criteria); OA of the knee is not to be secondary to any rheumatologic conditions (e.g., rheumatoid arthritis)
• Pain compatible with OA of the knee(s) for at least 26 weeks prior to screening
• Primary source of pain throughout the body is due to OA in the target knee
• Willingness to use an electronic diary on a daily basis in the evening for the screening period and 24-week study duration
• Negative drug test for opioids and drugs of abuse, except alcohol and marijuana, at screening
• Subjects with depression or anxiety must be clinically stable for 12 weeks prior to screening, and, if on treatment for depression or anxiety, be on 12 weeks of stable therapy
• 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

You may not qualify if:

• Women who are pregnant, lactating, or have a positive pregnancy result at screening
• Women of child bearing potential who are sexually active and are not willing to use a highly effective method of birth control during the study period
• Males who are sexually active and have a partner who is capable of becoming pregnant, neither of whom have had surgery to become sterilized or whom are not using a highly effective method of birth control
• Body mass index (BMI) \> 35
• Partial or complete joint replacement in either knee
• Currently requires regular use of ambulatory assistive devices (e.g., wheelchair, parallel bars, walker, canes, or crutches) or use of a lower extremity prosthesis, and/or a structural knee brace
• Previous participation in a Samumed clinical trial investigating SM04690
• Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to screening
• Any planned surgery during the study period
• 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 if completely excised. Subjects with other malignancies are eligible if they have been continuously disease free for at least 5 years prior to any study injection
• 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
• Any diagnosed psychiatric condition that includes, but is not limited to, a history of mania, bipolar disorder, psychotic disorder, schizophrenia, schizoaffective disorder, 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, or an observational research trial related to osteoarthritis within 8 weeks prior to any study injection, or planned participation in any such trial
• Treatment of the target knee with intra-articular glucocorticoids (e.g., methylprednisolone) within 12 weeks prior to screening
• Any intra-articular injection into the target knee with a therapeutic aim including, but not limited to, viscosupplementation (e.g., hyaluronic acid), platelet-rich plasma (PRP), and stem cell therapies within 24 weeks prior to screening; treatment of the target knee with intra-articular glucocorticoids greater than 12 weeks prior to screening is allowed

Sponsors & Collaborators

• Biosplice Therapeutics, Inc.: lead

Study Sites (74)

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Anniston, Alabama, 36207, United States

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Birmingham, Alabama, 35216, United States

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Mobile, Alabama, 36608, United States

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Chandler, Arizona, 85224, United States

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Phoenix, Arizona, 85018, United States

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Phoenix, Arizona, 85053, United States

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Tucson, Arizona, 85712, United States

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Anaheim, California, 92801, United States

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Canoga Park, California, 91303, United States

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Carmichael, California, 95608, United States

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Cerritos, California, 90703, United States

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El Cajon, California, 92020, United States

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Gold River, California, 95670, United States

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La Mesa, California, 91942, United States

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Los Angeles, California, 90036, United States

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Rancho Mirage, California, 92270, United States

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Sacramento, California, 95817, United States

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San Diego, California, 92103, United States

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San Marcos, California, 92078, United States

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Spring Valley, California, 91978, United States

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Boulder, Colorado, 80301, United States

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Stamford, Connecticut, 06905, United States

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Trumbull, Connecticut, 06606, United States

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Waterbury, Connecticut, 06708, United States

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Clearwater, Florida, 33761, United States

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Coral Gables, Florida, 33134, United States

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DeLand, Florida, 32720, United States

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Edgewater, Florida, 32132, United States

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Lauderdale Lakes, Florida, 33319, United States

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Miami, Florida, 33143, United States

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Pinellas Park, Florida, 33781, United States

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Marietta, Georgia, 30060, United States

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Woodstock, Georgia, 30189, United States

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Chicago, Illinois, 60607, United States

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Evansville, Indiana, 47714, United States

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Newton, Kansas, 67114, United States

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Prairie Village, Kansas, 66208, United States

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Wichita, Kansas, 67205, United States

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Lexington, Kentucky, 40504, United States

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Jefferson, Louisiana, 70121, United States

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Frederick, Maryland, 21702, United States

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Boston, Massachusetts, 02111, United States

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Troy, Michigan, 48085, United States

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City of Saint Peters, Missouri, 63303, United States

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Kansas City, Missouri, 64114, United States

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St Louis, Missouri, 63141, United States

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Lincoln, Nebraska, 68516, United States

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Las Vegas, Nevada, 89119, United States

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Albuquerque, New Mexico, 87102, United States

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Rochester, New York, 14609, United States

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Charlotte, North Carolina, 28209, United States

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Charlotte, North Carolina, 28210, United States

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High Point, North Carolina, 27262, United States

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Salisbury, North Carolina, 28144, United States

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Wilmington, North Carolina, 28401, United States

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Fargo, North Dakota, 58103, United States

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Cincinnati, Ohio, 45224, United States

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Cincinnati, Ohio, 45246, United States

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Cleveland, Ohio, 44122, United States

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Columbus, Ohio, 43213, United States

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Duncansville, Pennsylvania, 16635, United States

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Philadelphia, Pennsylvania, 19152, United States

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State College, Pennsylvania, 16801, United States

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Charleston, South Carolina, 29406, United States

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Mt. Pleasant, South Carolina, 29464, United States

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Rapid City, South Dakota, 57702, United States

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Austin, Texas, 78745, United States

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Bedford, Texas, 76021, United States

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Dallas, Texas, 75231, United States

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Houston, Texas, 77055, United States

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San Angelo, Texas, 76904, United States

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Arlington, Virginia, 22207, United States

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Charlottesville, Virginia, 22911, United States

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Danville, Virginia, 24541, United States

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Related Publications (4)

• Yazici Y, McAlindon TE, Gibofsky A, Lane NE, Lattermann C, Skrepnik N, Swearingen CJ, Simsek I, Ghandehari H, DiFrancesco A, Gibbs J, Tambiah JRS, Hochberg MC. A Phase 2b randomized trial of lorecivivint, a novel intra-articular CLK2/DYRK1A inhibitor and Wnt pathway modulator for knee osteoarthritis. Osteoarthritis Cartilage. 2021 May;29(5):654-666. doi: 10.1016/j.joca.2021.02.004. Epub 2021 Feb 12.

  PMID: 33588087 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

• Tambiah JRS, Simsek I, Swearingen CJ, Kennedy S, Cole BJ, McAlindon TE, Yazici Y. Comparing Patient-Reported Outcomes From Sham and Saline-Based Placebo Injections for Knee Osteoarthritis: Data From a Randomized Clinical Trial of Lorecivivint. Am J Sports Med. 2022 Mar;50(3):630-636. doi: 10.1177/03635465211067201. Epub 2022 Jan 10.

  PMID: 35005990 DERIVED

• Tambiah JRS, Kennedy S, Swearingen CJ, Simsek I, Yazici Y, Farr J, Conaghan PG. Individual Participant Symptom Responses to Intra-Articular Lorecivivint in Knee Osteoarthritis: Post Hoc Analysis of a Phase 2B Trial. Rheumatol Ther. 2021 Jun;8(2):973-985. doi: 10.1007/s40744-021-00316-w. Epub 2021 Jun 8.

  PMID: 34101138 DERIVED

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Interventions

lorecivivint; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Results Point of Contact

• Title: Christopher Swearingen, PhD, VP of Biometrics
• Organization: Biosplice Therapeutics, Inc.

chris.swearingen@biosplice.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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2017
• First Posted: April 21, 2017
• Study Start: April 24, 2017
• Primary Completion: April 30, 2018
• Study Completion: April 30, 2018
• Last Updated: June 11, 2021
• Results First Posted: May 18, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (74)