Clinical trial NCT04385303: A Study Utilizing Patient-Reported Outcomes to Evaluate the Safety and Efficacy of Lorecivivint (SM04690) for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis
Official title: A Phase 3, 28-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of a Single Injection of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Knee Osteoarthritis
Keywords: SM04690
Wnt pathway inhibitor
osteoarthritis
Samumed
lorecivivint
Lead sponsor: Biosplice Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-05-12
Enrollment: 498
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 3 study is a multicenter, randomized, double-blind, placebo-controlled study of lorecivivint injected intraarticularly (IA) into the target knee (most painful) joint of moderately to severely symptomatic osteoarthritis (OA) subjects at a single dose of 0.07 mg lorecivivint per 2 mL injection. This study will utilize patient reported outcomes (PROs) to evaluate the safety and efficacy of lorecivivint.


Eligibility criteria: Key Inclusion Criteria:

* Males and females between 40 and 80 years of age, inclusive, in general good health apart from their knee OA
* Ambulatory (single assistive devices such as canes allowed if needed less than 50% of the time, subjects requiring a walker are excluded)
* Diagnosis of femorotibial OA in the target knee by standard American College of Rheumatology (ACR) criteria at the Screening Visit (clinical AND radiographic criteria); OA of the knee is not to be secondary to any rheumatologic conditions (e.g., rheumatoid arthritis)
* Radiographic disease Stage 2 or 3 in target knee within 24 weeks of the Screening Visit according to the Kellgren-Lawrence (KL) grading of knee OA as assessed by independent central readers
* Qualifying mean score on the 24-h average pain score (0-10 numeric rating scale)
* Pain compatible with OA of the knee(s) for at least 26 weeks prior to the Screening Visit
* Primary source of pain throughout the body is due to OA in the target knee
* Body mass index (BMI) ≤ 35 kg/m2 at the Screening Visit
* Negative drug test for amphetamine, buprenorphine, cocaine, methadone, opiates, phencyclidine (PCP), propoxyphene, barbiturates, benzodiazepine, methaqualone, and tricyclic antidepressants, unless any of these drugs are allowed per protocol and prescribed by a physician to treat a specific condition

Key Exclusion Criteria:

* Pregnant women, breastfeeding women, and women who are not post-menopausal (defined as 12 months with no menses without an alternative medical cause) or permanently surgically sterile (includes hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) who have a positive or indeterminate pregnancy test result at the Screening Visit or Day 1
* Significant malalignment of anatomical axis (medial angle formed by the femur and tibia) of the target knee (varus \> 10°, valgus \> 10°) by radiograph within 24 weeks of the Screening Visit as assessed by independent central readers
* Partial or complete joint replacement in either knee
* Currently requires use of a lower extremity prosthesis, and/or a structural knee brace (i.e., a knee brace that contains hardware)
* Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to Day 1
* Intra-articular (IA) injection into the target knee with a therapeutic aim including, but not limited to hyaluronic acid, platelet-rich plasma (PRP), and stem cell therapies within 26 weeks prior to Day 1; or IA glucocorticoids within 12 weeks prior to Day 1 allowed
* Previous treatment with lorecivivint (SM04690)
* Subjects who have previously failed screening on this protocol and fail to meet re-screening criteria
* Participation in a clinical research trial that included the receipt of an investigational product or any experimental therapeutic procedure within 26 weeks prior to the Screening Visit, or planned participation in any such trial
* Subjects requiring the use of opioids \> 1x per week within 12 weeks prior to Day 1
* History of malignancy within the last 5 years; not including subjects with prior history of adequately treated in situ cervical cancer or basal or squamous cell skin cancer
* Clinically significant abnormal screening hematology values, blood chemistry values, or urinalysis values as determined by the Investigator
* Any known active infections, including urinary tract infection, upper respiratory tract infection, sinusitis, suspicion of IA infection, hepatitis B or hepatitis C infection, and/or infections that may compromise the immune system such as human immunodeficiency virus (HIV) at Day 1

Primary outcomes:
measure: Change from baseline OA pain in the target knee as assessed by the weekly average of daily pain numeric rating scale (NRS) at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change from baseline OA pain in the target knee as assessed by the weekly average of daily pain numeric rating scale (NRS) at Week 24
timeFrame: Baseline and Week 24
measure: Change from baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function subscore (WOMAC Function) at Weeks 12 and 24
timeFrame: Baseline, Weeks 12 and 24
measure: Change from baseline OA disease activity as assessed by Patient Global Assessment at Weeks 12 and 24
timeFrame: Baseline, Weeks 12 and 24
measure: Change from baseline in usage of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen for target knee OA pain at Week 24
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Birmingham
country: United States
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state: Alabama
city: Mobile
country: United States
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state: Alabama
city: Phoenix
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state: Arizona
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state: Arizona
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state: Arizona
city: Little Rock
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state: Arkansas
city: Anaheim
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state: California
city: Beverly Hills
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state: California
city: Canoga Park
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city: Garden Grove
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city: La Mesa
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city: Norco
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city: Westminster
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city: Boulder
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state: Colorado
city: Hamden
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state: Connecticut
city: Clearwater
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state: Florida
city: Edgewater
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city: Gulf Breeze
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city: Miami Lakes
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city: Winter Haven
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city: Winter Park
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facility: Research Site 1
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city: Marietta
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state: Georgia
city: Newnan
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state: Georgia
city: Woodstock
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state: Georgia
city: Boise
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state: Idaho
city: Chicago
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state: Illinois
city: Gurnee
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state: Illinois
city: Oak Brook
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state: Illinois
city: Evansville
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state: Indiana
city: Greenwood
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state: Indiana
city: Valparaiso
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state: Indiana
city: New Orleans
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state: Louisiana
city: Wheaton
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state: Maryland
city: Boston
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state: Massachusetts
city: Troy
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state: Michigan
city: Hazelwood
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state: Missouri
city: Kansas City
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state: Missouri
city: Saint Louis
country: United States
facility: Research Site 1
state: Missouri
city: Saint Louis
country: United States
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state: Missouri
city: Omaha
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state: Nebraska
city: Las Vegas
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state: Nevada
city: Reno
country: United States
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state: Nevada
city: Freehold
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state: New Jersey
city: Albuquerque
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state: New Mexico
city: Hartsdale
country: United States
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state: New York
city: Rochester
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state: New York
city: Greensboro
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state: North Carolina
city: Salisbury
country: United States
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state: North Carolina
city: Winston-Salem
country: United States
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state: North Carolina
city: Cincinnati
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state: Ohio
city: Edmond
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state: Oklahoma
city: Duncansville
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state: Pennsylvania
city: Charleston
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state: South Carolina
city: Fort Mill
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city: Mount Pleasant
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state: South Carolina
city: Rapid City
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state: South Dakota
city: Bellaire
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state: Texas
city: Carrollton
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city: Dallas
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state: Texas
city: Houston
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state: Texas
city: Plano
country: United States
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state: Texas
city: Draper
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state: Utah
city: Ogden
country: United States
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state: Utah
city: Salt Lake City
country: United States
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state: Utah
city: Charlottesville
country: United States
facility: Research Site
state: Virginia
city: Richmond
country: United States
facility: Research Site
state: Virginia
Study officials:
affiliation: Biosplice Therapeutics, Inc.
name: Yusuf Yazici, M.D.
role: STUDY_DIRECTOR
References: