Knee OsteoarthritisPhase 2NCT03706521
MRI Study to Evaluate the Safety and Efficacy of SM04690 for Knee Osteoarthritis
A Phase 2 study testing lorecivivint in people with Knee Osteoarthritis, run by Biosplice Therapeutics, Inc. at 1 site in United States.
Trial summary
The purpose of this study was to evaluate the safety and efficacy of lorecivivint (LOR) injected in the target knee joint of moderately to severely symptomatic osteoarthritis (OA) subjects. Efficacy was primarily evaluated via magnetic resonance imaging (MRI). Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Knee Osteoarthritis
- What is being tested?
- lorecivivint
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Mar 2019to 21 Dec 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
- 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
- Daily OA knee pain diary average Numeric Rating Scale (NRS) intensity score ≥4 and ≤8 in the target knee on the 11-point (0-10) NRS scale for the 7 days immediately preceding Day 1
- Pain NRS scores recorded for the target knee on at least 4 out of the 7 days immediately preceding Day 1
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- Daily OA knee pain diary average NRS intensity score <4 in the non-target knee on the 11-point (0-10) NRS scale for the 7 days immediately preceding Day 1
- Pain NRS scores recorded for the non-target knee on at least 4 out of the 7 days immediately preceding Day 1
- Baseline mJSW by radiograph between 2 and 4 mm, inclusive, in the target knee at the Screening Visit as assessed by independent central readers
- Total WOMAC score of 96-192 (out of 240) for the target knee at Day 1 regardless of if the subject is on symptomatic oral treatment
- Negative drug test for amphetamine, methamphetamine, buprenorphine, cocaine, methadone, opiates, phencyclidine (PCP), propoxyphene, barbiturates, benzodiazepine, methaqualone, and tricyclic antidepressants, except if any such drugs are clinically indicated and allowed by the protocol at the Screening Visit
- Subjects with depression or anxiety must be clinically stable for 12 weeks prior to the Screening Visit 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
- Subject's Screening Visit must occur while enrollment into the study is open
Who cannot join
- Women who are pregnant, lactating, or have a positive pregnancy test result at the Screening Visit
- Women of childbearing potential who are sexually active, and who are not willing to use an acceptable method of birth control during the study period
- Men of childbearing potential who are sexually active and have a partner who is capable of becoming pregnant, neither of whom are agreeable to using an acceptable method of birth control during the study period
- Body mass index (BMI) > 40
- Partial or complete joint replacement in either knee
- Currently requires: a) regular use (in the opinion of the Investigator) of ambulatory assistive devices (e.g., wheelchair, parallel bars, walker, canes, or crutches), or b) use of a lower extremity prosthesis, and/or a structural knee brace (i.e., a knee brace that contains hardware)
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- Radiographic disease Stage 0, 1, or 4 in the target knee at the Screening Visit according to the Kellgren-Lawrence (KL) grading of knee OA as assessed by independent central readers
- Previous treatment with lorecivivint (SM04690)
- Subjects who have previously failed screening on this protocol and fail to meet re-screening criteria
- Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to the Screening Visit
- Any surgery scheduled during the study period. Non-surgical invasive procedures conducted for a diagnostic or therapeutic purpose scheduled during the study period are not prohibited
- Significant and clinically evident misalignment of either knee that would impact subject function, as determined by the Investigator
- History of malignancy within the last 5 years; however, subjects with prior history of in situ 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 the Screening Visit
- Clinically significant abnormal screening hematology values, blood chemistry values, or urinalysis values as determined by the Investigator
- Any condition, including laboratory findings not included in the Screening Visit laboratory tests and findings in the medical history or in the pre-study assessments, 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
- 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
- Other conditions that, in the opinion of the Investigator, could affect study endpoint assessments of either knee, including, but not limited to, peripheral neuropathy (e.g., diabetic neuropathy), symptomatic hip osteoarthritis, symptomatic degenerative disc disease, and patellofemoral syndrome
- 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 to the Screening Visit, or planned participation in any such trial; the last date of participation in the trial, not the last date of receipt of investigational product, must be at least 8 weeks prior to the Screening Visit
- 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 the Screening Visit; treatment of the target knee with intra-articular glucocorticoids greater than 12 weeks prior to the Screening Visit is allowed
- Treatment with systemic glucocorticoids greater than 10 mg prednisone or the equivalent per day within 4 weeks prior to the Screening Visit
- Effusion of the target knee clinically requiring aspiration within 12 weeks prior to the Screening Visit
- Use of electrotherapy, acupuncture, and/or chiropractic treatments for knee OA within 4 weeks prior to the Screening Visit
- 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 Day 1
- Current use, or use within 12 weeks prior to the Screening Visit, of centrally acting analgesics
- Current use, or use within 12 weeks prior to the Screening Visit, of anticonvulsants (refer to Appendix 2)
- Subjects requiring the usage of opioids >1x per week within 12 weeks prior to the Screening Visit
- Topical local anesthetic agents (gels, creams, or patches such as the Lidoderm patch) used for the treatment of knee OA within 7 days of the Screening Visit
- Any chronic condition that has not been well controlled or subjects with a chronic condition who have not maintained a stable therapeutic regimen of a prescription therapy in the opinion of the investigator. In addition, subjects with an HbA1c >9 at the Screening Visit will be excluded.
- If on nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of OA pain, subjects who have not maintained a stable regimen in the opinion of the Investigator at the Screening Visit
- Any contraindications for performing MRI
- Subjects who have a current or pending disability claim, workers' compensation, or litigation(s) that may compromise response to treatment
- Subjects who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at any investigative site, or are directly affiliated with the study at any investigative site
- Subjects employed by Biosplice Therapeutics, Inc., or any of its affiliates or development partners (that is, an employee, temporary contract worker, or designee) responsible for the conduct of the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2, 52 Week, Single Center, Open-Label Study Utilizing Imaging Techniques and Evaluating the Safety and Efficacy of SM04690 Injectable Suspension for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis
The purpose of this study was to evaluate the safety and efficacy of lorecivivint (LOR) injected in the target knee joint of moderately to severely symptomatic osteoarthritis (OA) subjects. Efficacy was primarily evaluated via magnetic resonance imaging (MRI).
Read the detailed description
This phase 2 study was a single center, open-label study of lorecivivint (LOR) (internal identification SM04690) 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 LOR per 2 mL injection.
The primary objective was to evaluate the efficacy of LOR for the treatment of knee OA via magnetic resonance imaging (MRI) by assessing various cartilage health biomarkers, including cartilage thickness, cartilage volume, and cartilage quality and hydration markers.
The study was terminated early due to COVID-19-related issues (e.g., temporary site closures impacting data collection).
- Conditions
- Knee Osteoarthritis
- Being tested
- lorecivivint
- Keywords
- SM04690, Wnt pathway inhibitor, osteoarthritis, lorecivivint, Biosplice Therapeutics, Inc.
- Medical subject headings
- Osteoarthritis, Knee, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lorecivivintDrug
Also called SM04690
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study.
| Study group | Role | What they receive |
|---|---|---|
| Lorecivivint 0.07 mg | Experimental | Single intra-articular injection of lorecivivint (SM04690) 0.07 mg in 2 mL vehicle
lorecivivint: Healthcare professional-administered intra-articular injection performed once on Day 1 of the study. Receives: Drug: lorecivivint |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Medial Tibial Cartilage Thickness in the Target Knee as Measured by MRI
The assessment of hyaline cartilage thickness present in the knee joint can be useful in evaluating cartilage health. Cartilage thickness decreases may indicate knee osteoarthritis progression.
Cartilage thickness was measured using a semi-automated Local-Area Cartilage Segmentation (LACS) software for knee cartilage segmentation of knee MRI. The LACS coordinate system is based on anatomical bony landmarks and permits measurement within any subregion of the femorotibial joint consistently across longitudinal assessments.
Measured: Baseline and Week 26
Change From Baseline in Medial Tibial Cartilage Volume in the Target Knee as Measured by MRI
The assessment of hyaline cartilage volume present in the knee joint can be useful in evaluating cartilage health. Cartilage volume decreases may indicate knee osteoarthritis progression.
Cartilage volume was measured using a semi-automated Local-Area Cartilage Segmentation (LACS) software for knee cartilage segmentation of knee MRI. The LACS coordinate system is based on anatomical bony landmarks and permits measurement within any subregion of the femorotibial joint consistently across longitudinal assessments.
Measured: Baseline and Week 26
Change From Baseline in Average T1 Rho for the Medial Tibial Cartilage of Target Knee
T1rho mapping refers to an investigational magnetic resonance imaging technique that measures the low-frequency interactions between macromolecules such as proteoglycan and glycosaminoglycan and water, useful for evaluating cartilage health. Increase in T1rho measurements over time can represent cartilage degeneration.
Measured: Baseline and Week 26
Change From Baseline in Average T2 Mapping in Medial Tibial Cartilage of Target Knee
T2 mapping refers to an investigational magnetic resonance imaging technique that measures biochemical changes in cartilage, including the integrity of collagen network, and collagen and water content, useful for evaluating cartilage health. Increase in T2 mapping measurements over time can represent cartilage degeneration.
Measured: Baseline and Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2018
- Study start11 Mar 2019
- Primary completion22 Jul 2020
- Study completion21 Dec 2020
Why it stopped: The study was terminated early due to COVID-19 pandemic-related issues (e.g., temporary site closures impacting data collection). No formal Statistical Analysis Plan was prepared, and the study report was finalized without any statistical analysis.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Knee OsteoarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biosplice Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yusuf Yazici, M.D., Study director, Biosplice Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03706521
- Sponsor's protocol ID
- SM04690-OA-08
- Status last verified
- Feb 2026
- First submitted
- 11 Oct 2018
- Last updated
- 4 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, 52 Week, Single Center, Open-Label Study Utilizing Imaging Techniques and Evaluating the Safety and Efficacy of SM04690 Injectable Suspension for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis
- ClinicalTrials.gov ID
- NCT03706521
- Acronym / sponsor ID
- SM04690-OA-08
- Conditions
- Knee Osteoarthritis
- Keywords
- SM04690, Wnt pathway inhibitor, osteoarthritis, lorecivivint, Biosplice Therapeutics, Inc.
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated early due to COVID-19 pandemic-related issues (e.g., temporary site closures impacting data collection). No formal Statistical Analysis Plan was prepared, and the study report was finalized without any statistical analysis.
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Biosplice Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 11 Mar 2019 (actual)
- Primary completion
- 22 Jul 2020 (actual)
- Study completion
- 21 Dec 2020 (actual)
- First posted
- 16 Oct 2018 (actual)
- Results
- Posted 4 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to evaluate the safety and efficacy of lorecivivint (LOR) injected in the target knee joint of moderately to severely symptomatic osteoarthritis (OA) subjects. Efficacy was primarily evaluated via magnetic resonance imaging (MRI).
Detailed description
This phase 2 study was a single center, open-label study of lorecivivint (LOR) (internal identification SM04690) 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 LOR per 2 mL injection.
The primary objective was to evaluate the efficacy of LOR for the treatment of knee OA via magnetic resonance imaging (MRI) by assessing various cartilage health biomarkers, including cartilage thickness, cartilage volume, and cartilage quality and hydration markers.
The study was terminated early due to COVID-19-related issues (e.g., temporary site closures impacting data collection).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lorecivivint 0.07 mg | Experimental | Drug: lorecivivintSingle intra-articular injection of lorecivivint (SM04690) 0.07 mg in 2 mL vehicle lorecivivint: Healthcare professional-administered intra-articular injection performed once on Day 1 of the study. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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)
- 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
- Daily OA knee pain diary average Numeric Rating Scale (NRS) intensity score ≥4 and ≤8 in the target knee on the 11-point (0-10) NRS scale for the 7 days immediately preceding Day 1
Key exclusion criteria (34 listed)
- Women who are pregnant, lactating, or have a positive pregnancy test result at the Screening Visit
- Women of childbearing potential who are sexually active, and who are not willing to use an acceptable method of birth control during the study period
- Men of childbearing potential who are sexually active and have a partner who is capable of becoming pregnant, neither of whom are agreeable to using an acceptable method of birth control during the study period
- Body mass index (BMI) > 40
- Partial or complete joint replacement in either knee
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lorecivivintAlso: SM04690Healthcare professional-administered intra-articular injection performed once on Day 1 of the study. | Drug | Lorecivivint 0.07 mg |
Primary outcome
Change From Baseline in Medial Tibial Cartilage Thickness in the Target Knee as Measured by MRI
Time frame: Baseline and Week 26
The assessment of hyaline cartilage thickness present in the knee joint can be useful in evaluating cartilage health. Cartilage thickness decreases may indicate knee osteoarthritis progression. Cartilage thickness was measured using a semi-automated Local-Area Cartilage Segmentation (LACS) software for knee cartilage segmentation of knee MRI. The LACS coordinate system is based on anatomical bony landmarks and permits measurement within any subregion of the femorotibial joint consistently across longitudinal assessments.
Change From Baseline in Medial Tibial Cartilage Volume in the Target Knee as Measured by MRI
Time frame: Baseline and Week 26
The assessment of hyaline cartilage volume present in the knee joint can be useful in evaluating cartilage health. Cartilage volume decreases may indicate knee osteoarthritis progression. Cartilage volume was measured using a semi-automated Local-Area Cartilage Segmentation (LACS) software for knee cartilage segmentation of knee MRI. The LACS coordinate system is based on anatomical bony landmarks and permits measurement within any subregion of the femorotibial joint consistently across longitudinal assessments.
Change From Baseline in Average T1 Rho for the Medial Tibial Cartilage of Target Knee
Time frame: Baseline and Week 26
T1rho mapping refers to an investigational magnetic resonance imaging technique that measures the low-frequency interactions between macromolecules such as proteoglycan and glycosaminoglycan and water, useful for evaluating cartilage health. Increase in T1rho measurements over time can represent cartilage degeneration.
Change From Baseline in Average T2 Mapping in Medial Tibial Cartilage of Target Knee
Time frame: Baseline and Week 26
T2 mapping refers to an investigational magnetic resonance imaging technique that measures biochemical changes in cartilage, including the integrity of collagen network, and collagen and water content, useful for evaluating cartilage health. Increase in T2 mapping measurements over time can represent cartilage degeneration.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yusuf Yazici, M.D. study director
Biosplice Therapeutics, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing lorecivivint in people with Knee Osteoarthritis, run by Biosplice Therapeutics, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Medial Tibial Cartilage Thickness in the Target Knee as Measured by MRI (time frame: Baseline and Week 26). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2026.