Osteoarthritis, Knee
Conditions
Keywords
SM04690, DYRK inhibitor, CLK inhibitor, Wnt pathway inhibitor, osteoarthritis, Biosplice Therapeutics, Inc., Samumed, lorecivivint
Brief summary
Study OA-07 was a randomized, double-blind, placebo-controlled, Phase 3, multicenter, 2-year clinical trial that enrolled subjects from the recently completed Study OA-11 (NCT03928184). The first 48 weeks of OA-07 the trial was placebo-controlled with subjects receiving the same randomized treatment received in OA-11. Investigators, research staff and subjects remained blinded to treatment allocation. At Week 48, all subjects were administered LOR in the open-label portion of the trial.
Detailed description
At Visit 1E (on Day 1), upon completion of initial study procedures (e.g., informed consent, eligibility requirements, clinical evaluations including pregnancy testing \[as applicable\], baseline patient-reported outcome \[PRO\] assessments and safety data collection), subjects received a blinded IA injection of either LOR or PBO (as originally randomized in the parent \[OA-11\] study) into their target knee. At Visit 3E (Week 48), upon completion of scheduled clinical, medical, safety and Patient-reported outcome (PRO) assessments, all subjects received an open-label injection of IA LOR into their target knee, such that previously PBO-treated subjects were effectively crossed over to the LOR treatment cohort. Subjects were given the option to either receive a final injection of IA LOR into their target knee and complete both Visit 6E (Week 100) assessments and End-of-Study Visit assessments, or receive no injection and complete End-of-Study Visit assessments only. Subjects who had completed Visit 6E prior to the announcement of study closure were instructed to return to the clinic for End-of-Study Visit assessments. Study OA-07's initial study design was to assess the safety and efficacy of additional treatment with LOR compared to PBO over one year and conclude at Visit 3E. The study was amended to become an open-label study at the Visit 3E that included an End-of-Study visit but without a specified time. The study was intended and described in the protocol to be run until such time as the Sponsor chose to close it. Study OA-07 was administratively closed at Visit 6E (Week 100), with no safety concerns, one year into the open-label study. For these reasons, Study OA-07 is considered a completed study.
Interventions
DRUGPlacebo
Healthcare professional-administered intra-articular injection of vehicle.
DRUGLorecivivint
Healthcare professional-administered intra-articular injections of lorecivivint.
Sponsors
Biosplice Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The first 48 weeks were research site personnel (investigator, coordinators, assessors) and subjects were blinded to the treatment assignment. After Week 48, the remainder of the study was open-label with all subjects receiving LOR study injections.
Eligibility
Sex/Gender
ALL
Age
41 Years to 81 Years
Healthy volunteers
No
Inclusion criteria
1. Completion of the Study SM04690-OA-11 (NCT03928184) 2. Compliance with procedures in study SM04690-OA-11, in the opinion of the Investigator 3. Fully understanding study requirements and willingness to comply with study visits and assessments 4. Understanding and signing of the informed consent form (ICF) prior to any study-related procedures
Exclusion criteria
1. 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 2. Any contraindications for an intra-articular (IA) injection in the target knee in the opinion of the Investigator 3. Any known reason identified by the Investigator or Sponsor that the subject may not be compliant with study visits or may no longer be an appropriate candidate for the study (e.g. planned major surgery, knee replacement during the parent study, planning to move away from the research site, or initiation of a prohibited concomitant medication including, but not limited to, IA injection of glucocorticoids, hyaluronic acid derivatives, platelet-rich plasma, stem cell therapies, or other agents with therapeutic intent into the target knee) 4. Participation in a clinical research trial (other than the prior SM04690-OA-11 study) that included the receipt of an investigational product (IP) or any experimental therapeutic procedure within 12 weeks before any study injection, or planned participation in any such trial 5. Current or pending disability claim, workers' compensation, or litigation(s) that may compromise response to treatment 6. 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 Visit 1E (Day 1) 7. Women who are not post-menopausal or permanently surgically sterile who are sexually active, and who are not willing to use birth control (as outlined in the protocol) during the study period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From OA-11-study Baseline Medial Joint Space Width (mJSW) in the Target Knee | OA-11-study baseline; Visit 3E (Week 48) | Change from OA-11-study baseline in mJSW measured in millimeters as documented by radiograph (X-ray) of the target knee. JSW measurements were provided by a blinded, central imaging vendor using landmark-based, computer-assisted proprietary methodology. |
| Change From OA-07-study Baseline OA Pain in the Target Knee | OA-07-study baseline; Visit 2E (Week 24) | Change from OA-07-study baseline OA pain the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain). 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 ranges from 0 \[no pain\] to 100 \[pain as bad as it can be\]. |
| Change From OA-07-study Baseline OA Function in the Target Knee | OA-07-study baseline; Visit 2E (Week 24) | Change from OA-07-study baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) physical functioning subscore (WOMAC Function). 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 ranges from 0 \[highest functional status\] to 100 \[most impaired functional status\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From OA-07-study Baseline OA Pain in the Target Knee | OA-07-study baseline; Visit 3E (Week 48) | Change from OA-07-study baseline OA pain the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain). 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 ranges from 0 \[no pain\] to 100 \[pain as bad as it can be\]. |
| Change From OA-07-study Baseline OA Function in the Target Knee | OA-07-study baseline; Visit 3E (Week 48) | Change from OA-07-study baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) physical functioning subscore (WOMAC Function). 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 ranges from 0 \[highest functional status\] to 100 \[most impaired functional status\]. |
Countries
United States
Contacts
STUDY_DIRECTORIsmail Simsek, MD
Biosplice Therapeutics, Inc.
Participant flow
Recruitment details
Subjects who completed Study OA-11 were invited to participate in Study OA-07
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 60.5 years STANDARD_DEVIATION 7.7 |
| Body Mass Index | 31.79 kg/m^2 STANDARD_DEVIATION 4.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 116 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Kellgren-Lawrence Grade Grade 2 | 74 Participants |
| Kellgren-Lawrence Grade Grade 3 | 125 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 71 Participants |
| Race (NIH/OMB) More than one race | 4 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 | 96 Participants |
| Region of Enrollment United States | 276 participants |
| Sex: Female, Male Female | 173 Participants |
| Sex: Female, Male Male | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 138 | 0 / 138 | 0 / 118 | 1 / 110 |
| other Total, other adverse events | 19 / 138 | 23 / 138 | 12 / 118 | 19 / 110 |
| serious Total, serious adverse events | 2 / 138 | 1 / 138 | 2 / 118 | 4 / 110 |
Outcome results
None listed