Knee Osteoarthritis
Conditions
Brief summary
This phase 3 study was a multicenter, randomized, double-blind, placebo-controlled study of lorecivivint injected intra-articularly (IA) into the target (most painful) knee joint of moderately to severely symptomatic osteoarthritis (OA) subjects at a single dose of 0.07 mg lorecivivint per 2 mL injection. This study utilized standard outcomes to evaluate the safety and efficacy of lorecivivint.
Detailed description
SM04690-OA-21 was a phase 3, 16-week multicenter, randomized, double-blind, placebo-controlled, parallel group study investigating the safety, tolerability and efficacy of LOR 0.07 mg (compared with PBO) injected into the target knee joint of moderately to severely symptomatic knee OA subjects. Patient-reported outcomes included Pain Numeric Rating Scale (NRS) \[0-10\], Western Ontario and McMaster Universities Arthritis Index (WOMAC), and Patient Global Assessment (PGA) of knee osteoarthritis. The primary efficacy endpoint was change from baseline in target knee Pain NRS at Week 12. Secondary endpoints included change at Week 12 in WOMAC Function and PGA.
Interventions
DRUGLorecivivint
One intra-articular injection of 0.07 mg lorecivivint in 2 mL vehicle
DRUGPlacebo
One intra-articular injection of 0 mg lorecivivint in 2 mL vehicle
Sponsors
Biosplice Therapeutics, Inc.
NBCD A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
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
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 * 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) * 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 * Use of APAP or NSAIDs during washout period (between Screening Visit 2 and Day 1). Use of aspirin (up to 325 mg/day) for thrombosis prophylaxis is permitted.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline OA Pain in the Target Knee as Assessed by Weekly Average of Daily Pain Numeric Rating Scale (NRS) at Week 12 | Baseline to Week 12 | Evaluate change from baseline OA pain in the target knee as assessed by 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 indicates pain as bad as you can imagine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline OA Function as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscore (WOMAC Function) at Week 12 | Baseline and Week 12 | Evaluate change from baseline OA function as assessed by WOMAC Function at Week 12. The WOMAC is a widely-used, proprietary outcome measurement tool used 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 an 11-point NRS scale \[0-10\], where 0 indicates no pain / no stiffness / no difficulty, and 10 indicates extreme pain / extreme stiffness / extreme difficulty. For analysis, WOMAC Function scores were scaled to 0 to 100, where 0 represents "No Functional Difficulty" and 100 represents "Extreme Functional Difficulty". |
| Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment at Week 12 | Baseline and Week 12 | Evaluate change from baseline OA disease activity as assessed by Patient Global Assessment at Week 12. The Patient Global Assessment is an 11-point NRS \[0-10\] for subject self-reporting of how they feel their target knee is impacting them. For analysis, PGA scores were scaled to 0 to 100, where 0 represents "Very Good" and 100 represents "Very Bad". |
Countries
United States
Contacts
STUDY_DIRECTORYusuf Yazici, MD
Biosplice Therapeutics, Inc.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 60.4 years STANDARD_DEVIATION 8.7 |
| Body Mass Index | 28.87 kg / m^2 STANDARD_DEVIATION 3.82 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 316 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 173 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Kellgren-Lawrence Grade Grade 2 | 488 Participants |
| Kellgren-Lawrence Grade Grade 3 | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 46 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 384 Participants |
| Sex: Female, Male Female | 156 Participants |
| Sex: Female, Male Male | 95 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 242 | 0 / 249 |
| other Total, other adverse events | 37 / 242 | 26 / 249 |
| serious Total, serious adverse events | 2 / 242 | 3 / 249 |
Outcome results
None listed