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

Knee Osteoarthritis Clinical Trial

Official title:

A Phase 2, 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03122860
• Other study ID #: SM04690-OA-04
• Status: Completed
• Phase: Phase 2
• Start date: April 24, 2017
• Est. completion date: April 30, 2018

Study information

• Verified date: May 2021
• Source: Biosplice Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 700
• Est. completion date: April 30, 2018
• Est. primary completion date: April 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Treatment with systemic glucocorticoids greater than 10 mg prednisone or the equivalent per day within 4 weeks prior to screening
• Effusion of the target knee clinically requiring aspiration within 12 weeks prior to screening
• Use of electrotherapy, acupuncture, and/or chiropractic treatments for knee OA within 4 weeks prior to screening
• Any known active infections, including urinary tract infection, upper respiratory tract infection, sinusitis, 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) at study start
• Use of centrally acting analgesics (e.g., duloxetine) within 12 weeks prior to screening
• Use of anticonvulsants within 12 weeks prior to screening, unless used for seizure or migraine prophylaxis
• Subjects requiring the usage of opioids >1x per week within 12 weeks prior to screening
• Use of topical local anesthetic agents (gels, creams, or patches such as the Lidoderm patch) for the treatment of knee OA within 7 days of screening

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• SM04690
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study

Other:
• Placebo
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study
• Sham
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study

Locations

Country	Name	City	State
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Anaheim	California
United States	Research Site	Anniston	Alabama
United States	Research Site	Arlington	Virginia
United States	Research Site	Austin	Texas
United States	Research Site	Bedford	Texas
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boulder	Colorado
United States	Research Site	Canoga Park	California
United States	Research Site	Carmichael	California
United States	Research Site	Cerritos	California
United States	Research Site	Chandler	Arizona
United States	Research Site	Charleston	South Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Clearwater	Florida
United States	Research Site	Cleveland	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Coral Gables	Florida
United States	Research Site	Dallas	Texas
United States	Research Site	Danville	Virginia
United States	Research Site	DeLand	Florida
United States	Research Site	Duncansville	Pennsylvania
United States	Research Site	Edgewater	Florida
United States	Research Site	El Cajon	California
United States	Research Site	Evansville	Indiana
United States	Research Site	Fargo	North Dakota
United States	Research Site	Frederick	Maryland
United States	Research Site	Gold River	California
United States	Research Site	High Point	North Carolina
United States	Research Site	Houston	Texas
United States	Research Site	Jefferson	Louisiana
United States	Research Site	Kansas City	Missouri
United States	Research Site	La Mesa	California
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lauderdale Lakes	Florida
United States	Research Site	Lexington	Kentucky
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Los Angeles	California
United States	Research Site	Marietta	Georgia
United States	Research Site	Miami	Florida
United States	Research Site	Mobile	Alabama
United States	Research Site	Mount Pleasant	South Carolina
United States	Research Site	Newton	Kansas
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pinellas Park	Florida
United States	Research Site	Prairie Village	Kansas
United States	Research Site	Rancho Mirage	California
United States	Research Site	Rapid City	South Dakota
United States	Research Site	Rochester	New York
United States	Research Site	Sacramento	California
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Peters	Missouri
United States	Research Site	Salisbury	North Carolina
United States	Research Site	San Angelo	Texas
United States	Research Site	San Diego	California
United States	Research Site	San Marcos	California
United States	Research Site	Spring Valley	California
United States	Research Site	Stamford	Connecticut
United States	Research Site	State College	Pennsylvania
United States	Research Site	Troy	Michigan
United States	Research Site	Trumbull	Connecticut
United States	Research Site	Tucson	Arizona
United States	Research Site	Waterbury	Connecticut
United States	Research Site	Wichita	Kansas
United States	Research Site	Wilmington	North Carolina
United States	Research Site	Woodstock	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Biosplice Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change From Baseline OA Pain in the Target Knee as Assessed by 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 12. 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 12
Other	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 12. 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 12
Other	Change From Baseline OA Pain in the Target Knee as Assesses by the Weekly Average of Daily Pain NRS	Change from baseline OA pain in the target knee as assessed by the weekly average of daily pain NRS at Week 12. 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 12
Other	Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA)	Change from baseline OA disease activity as assessed by PtGA at Week 12. The PtGA 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 12
Primary	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
Primary	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
Primary	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
Primary	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	Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA)	Change from baseline OA disease activity as assessed by PtGA at Week 24. The PtGA 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 24