Clinical trial NCT03122860: A Study Evaluating the Safety and Efficacy of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Knee Osteoarthritis
Keywords: SM04690
Wnt pathway inhibitor
osteoarthritis
Samumed
Lead sponsor: Biosplice Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2017-04-21
Enrollment: 700
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: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline Osteoarthritis (OA) Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS)
timeFrame: Baseline and Week 24
measure: Change From Baseline OA Pain in the Target Knee as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain)
timeFrame: Baseline and Week 24
measure: Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function)
timeFrame: Baseline and Week 24
measure: Change From Baseline in Medial Joint Space Width (mJSW) of the Target Knee
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA)
timeFrame: Baseline and Week 24
Other outcomes:
measure: Change From Baseline OA Pain in the Target Knee as Assessed by WOMAC Pain Subscore (WOMAC Pain)
timeFrame: Baseline and Week 12
measure: Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function)
timeFrame: Baseline and Week 12
measure: Change From Baseline OA Pain in the Target Knee as Assesses by the Weekly Average of Daily Pain NRS
timeFrame: Baseline and Week 12
measure: Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA)
timeFrame: Baseline and Week 12
Locations:
city: Anniston
country: United States
facility: Research Site
state: Alabama
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Mobile
country: United States
facility: Research Site
state: Alabama
city: Chandler
country: United States
facility: Research Site
state: Arizona
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Anaheim
country: United States
facility: Research Site
state: California
city: Canoga Park
country: United States
facility: Research Site
state: California
city: Carmichael
country: United States
facility: Research Site
state: California
city: Cerritos
country: United States
facility: Research Site
state: California
city: El Cajon
country: United States
facility: Research Site
state: California
city: Gold River
country: United States
facility: Research Site
state: California
city: La Mesa
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Rancho Mirage
country: United States
facility: Research Site
state: California
city: Sacramento
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: San Marcos
country: United States
facility: Research Site
state: California
city: Spring Valley
country: United States
facility: Research Site
state: California
city: Boulder
country: United States
facility: Research Site
state: Colorado
city: Stamford
country: United States
facility: Research Site
state: Connecticut
city: Trumbull
country: United States
facility: Research Site
state: Connecticut
city: Waterbury
country: United States
facility: Research Site
state: Connecticut
city: Clearwater
country: United States
facility: Research Site
state: Florida
city: Coral Gables
country: United States
facility: Research Site
state: Florida
city: DeLand
country: United States
facility: Research Site
state: Florida
city: Edgewater
country: United States
facility: Research Site
state: Florida
city: Lauderdale Lakes
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Pinellas Park
country: United States
facility: Research Site
state: Florida
city: Marietta
country: United States
facility: Research Site
state: Georgia
city: Woodstock
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Evansville
country: United States
facility: Research Site
state: Indiana
city: Newton
country: United States
facility: Research Site
state: Kansas
city: Prairie Village
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: Jefferson
country: United States
facility: Research Site
state: Louisiana
city: Frederick
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Troy
country: United States
facility: Research Site
state: Michigan
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Saint Peters
country: United States
facility: Research Site
state: Missouri
city: Lincoln
country: United States
facility: Research Site
state: Nebraska
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Rochester
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: High Point
country: United States
facility: Research Site
state: North Carolina
city: Salisbury
country: United States
facility: Research Site
state: North Carolina
city: Wilmington
country: United States
facility: Research Site
state: North Carolina
city: Fargo
country: United States
facility: Research Site
state: North Dakota
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Duncansville
country: United States
facility: Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: State College
country: United States
facility: Research Site
state: Pennsylvania
city: Charleston
country: United States
facility: Research Site
state: South Carolina
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: Austin
country: United States
facility: Research Site
state: Texas
city: Bedford
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: San Angelo
country: United States
facility: Research Site
state: Texas
city: Arlington
country: United States
facility: Research Site
state: Virginia
city: Charlottesville
country: United States
facility: Research Site
state: Virginia
city: Danville
country: United States
facility: Research Site
state: Virginia
Study officials:
affiliation: Biosplice Therapeutics, Inc.
name: Yusuf Yazici, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.