Osteoarthritis of the Knee
Conditions
Keywords
SM04690, Wnt pathway inhibitor, osteoarthritis, Biosplice Therapeutics, Inc., Lorecivivint, DYRK inhibitor, CLK inhibitor, Samumed
Brief summary
This study is designed as a 3-year, multicenter, open-label study evaluating the safety, tolerability, and efficacy of intra-articular (IA) Lorecivivint (LOR) in subjects with osteoarthritis of the knee in a real-world setting.
Detailed description
At Day 1, after a screening period of up to 14 days, subjects will receive an IA injection of 0.07 mg LOR into one or both knees, followed by a 36-month evaluation period. Clinic visits will be scheduled at Day 1, and Months 3, 12, 24, and 36 \[End of study (EOS)\] or Early Termination (ET). All Patient Reported Outcome (PRO) measurements, including Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and Pain Numeric Rating Scale (NRS), as well as safety evaluations will be conducted at each clinic visit. An additional phone follow-up visit for safety will occur 4 weeks after the injection on Day 1. Study was terminated by Sponsor based on a business decision not due to safety. The study report was finalized without any statistical analysis.
Interventions
DRUGLorecivivint
Healthcare professional-administered intra-articular (IA) injection into one or both knees as clinically indicated. Bilateral injections of 0.07 mg of LOR are allowed. IA injection performed on Day 1. Additional IA injections of LOR to same knee (with at least a 6 month separation) between Day 1 and Month 33.
Sponsors
Biosplice Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females between 40 and 80 years of age, inclusive, in general good health apart from their knee OA 2. Femorotibial OA by standard American College of Rheumatology (ACR) criteria; knee OA is not to be secondary to any rheumatologic conditions (e.g., rheumatoid arthritis). 3. Pain compatible with knee OA for at least 26 weeks prior to the Screening Visit 4. Negative drug test for amphetamine, buprenorphine, cocaine, methadone, opiates, phencyclidine (PCP), propoxyphene, barbiturates, and benzodiazepine, unless any of these drugs are prescribed by a physician to treat a specific condition 5. Full understanding of the requirements of the study and willingness to comply with all study visits and assessments 6. Subjects must have read and understood the informed consent form (ICF), and must have signed and dated it prior to any study-related procedure being performed
Exclusion criteria
1. 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 Screening and Day 1 2. Women who are not post-menopausal or permanently surgically sterile who are sexually active, and who are not willing to use birth control during the study period 3. Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to Day 1 4. Intra-articular (IA) injection into either 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 5. Any condition that, in the opinion of the Investigator, constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation 6. Any comorbid condition that could affect study endpoint assessments of the knee, including, but not limited to, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, gout or pseudogout, and fibromyalgia 7. Any contraindications for an IA injection in the knee(s) to be injected at Day 1 in the opinion of the Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Pain Numeric Rating Scale (NRS) Score for the Left Knee | Three Months after Day 1 Injection | Change from baseline in pain numeric rating scale (NRS) score for the left knee. 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. Change was calculated as three-month visit minus baseline; a negative value indicates improvement while a positive value indicates worsening. |
| Change From Baseline in Pain Numeric Rating Scale (NRS) Score for the Right Knee | Three Months after Day 1 Injection | Change from baseline in pain numeric rating scale (NRS) score for the right knee. 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. Change was calculated as three-month visit minus baseline; a negative value indicates improvement while a positive value indicates worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscore (WOMAC Function) in Left Knee | Three Months after Day 1 Injection | Change from baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index NRS3.1 physical function subscore (WOMAC Function) in left knee. 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, stiffness, and physical functioning of a target joint. 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 ranges from 0 to 170 (raw) and will be scaled 0 to 100 for reporting. Change was calculated as three-month visit minus baseline; a negative value indicates improvement while a positive value indicates worsening. |
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscore (WOMAC Function) in Right Knee | Three Months after Day 1 Injection | Change from baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index NRS3.1 physical function subscore (WOMAC Function) in right knee. 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, stiffness, and physical functioning of a target joint. 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 ranges from 0 to 170 (raw) and will be scaled 0 to 100 for reporting. Change was calculated as three-month visit minus baseline; a negative value indicates improvement while a positive value indicates worsening. |
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain) in Left Knee | Three Months after Day 1 Injection | Change from baseline OA pain in the target knee as assessed by Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index NRS3.1 pain subscore (WOMAC Pain) in left knee. 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, stiffness, and physical functioning of a target joint. 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 ranges from 0 to 50 (raw) and will be scaled 0 to 100 for reporting. Change was calculated as three-month visit minus baseline; a negative value indicates improvement while a positive value indicates worsening. |
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain) in Right Knee | Three Months after Day 1 Injection | Change from baseline OA pain in the target knee as assessed by Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index NRS3.1 pain subscore (WOMAC Pain) in right knee. 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, stiffness, and physical functioning of a target joint. 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 ranges from 0 to 50 (raw) and will be scaled 0 to 100 for reporting. Change was calculated as three-month visit minus baseline; a negative value indicates improvement while a positive value indicates worsening. |
Countries
United States
Contacts
STUDY_DIRECTORYusuf Yazici, MD
Biosplice Therapeutics, Inc.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 61.5 years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 58 Participants |
| Sex: Female, Male Female | 42 Participants |
| Sex: Female, Male Male | 30 Participants |
| Symptomatic OA Laterality by Investigator Assessment Bilateral | 58 Participants |
| Symptomatic OA Laterality by Investigator Assessment Unilateral, Left | 4 Participants |
| Symptomatic OA Laterality by Investigator Assessment Unilateral, Right | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 72 |
| other Total, other adverse events | 2 / 72 |
| serious Total, serious adverse events | 0 / 72 |
Outcome results
None listed