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Knee OsteoarthritisPhase 2NCT03727022

Safety and Bone Health Study of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis

A Phase 2 study testing SM04690 in people with Knee Osteoarthritis, run by Biosplice Therapeutics, Inc. at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The primary purpose of this phase 2, placebo-controlled, double-blind, parallel group study was to provide an initial safety evaluation of two intra-articular (IA) injections of SM04690 (each at the dose of 0.07mg per 2mL injection) approximately six months apart into the target knee of moderately to severely… 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?
SM04690
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
101 participants
Where
13 sitesUnited States
Study dates
28 Nov 2018to 18 Aug 2021
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

  • Males and females between 40 and 80 years of age, inclusive, in general good health
  • Ambulatory
  • Diagnosis of femorotibial OA in the target knee by standard American College of Rheumatology (ACR) criteria at Screening Visit 1 (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 Screening Visit 1
  • Primary source of pain throughout the body is due to OA in the target knee
  • Daily OA knee pain diary average 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
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  • Pain NRS scores recorded for the target knee on at least 4 out of the 7 days immediately preceding Day 1
  • 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
  • WOMAC pain subscore of 20-40 (out of 50) and WOMAC physical function subscore of 68-136 (out of 170) for the target knee at baseline, regardless of if the subject is on symptomatic oral treatment (baseline questionnaire completed during the screening period prior to randomization)
  • Widespread Pain Index (WPI) score of ≤ 4 and a Symptom Severity Question 2 (SSQ2) score of ≤ 2 at Screening Visit 1
  • Willingness to use an electronic diary on a daily basis in the evening for the screening period and 104-week study duration
  • Negative drug test for amphetamine, 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 Screening Visit 1.
  • Subjects with depression or anxiety must be clinically stable for 12 weeks prior to Screening Visit 1 in the opinion of the Investigator 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 (ICF), and must have signed and dated it prior to any study-related procedure being performed
  • Subject's Screening Visit 1 visit must occur while enrollment into the study is open
  • Subject is able to have a Screening Visit 2 qCT image acquired that does not require a re-scan as determined by the central imaging vendor

Who cannot join

  • Pregnant and 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) and have a positive or indeterminate pregnancy result at Screening Visit 2 or Day 1
  • 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 Section 5.3.1) during the study period
  • Males who are sexually active and have a partner who is capable of becoming pregnant, neither of whom have had surgery to become sterilized or who are not using birth control as outlined in Section 5.3.1
  • Body mass index (BMI) > 35
  • Partial or complete joint replacement in either knee
  • Currently requires:
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  • regular use (in the opinion of the Investigator) of ambulatory assistive devices (e.g., wheelchair, parallel bars, walker, canes, or crutches), or
  • use of a lower extremity prosthesis, and/or a structural knee brace (i.e., a knee brace that contains hardware)
  • Radiographic disease Stage 0, 1, or 4 in the target knee at Screening Visit 1 according to the Kellgren-Lawrence grading of knee OA as assessed by independent central readers
  • Previous enrollment in a Samumed clinical trial investigating SM04690
  • Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to Screening Visit 1
  • Any bone fracture(s) within 26 weeks prior to Screening Visit 1
  • 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.(refer to section 7.6)
  • 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 Screening Visit 1
  • 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 2 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
  • 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 (IP) or any experimental therapeutic procedure within 26 weeks prior to Screening Visit 1, or planned participation in any such trial
  • Treatment of the target knee with intra-articular glucocorticoids (e.g., methylprednisolone) within 12 weeks prior to Screening Visit 1
  • 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 Screening Visit 1; treatment of the target knee with intra-articular glucocorticoids greater than 12 weeks prior to Screening Visit 1 is allowed
  • Treatment with systemic (oral, intramuscular, or intravenous) glucocorticoids greater than 10 mg prednisone or the equivalent per day within 4 weeks prior to Screening Visit 1
  • Effusion of the target knee clinically requiring aspiration within 12 weeks prior to Screening Visit 1
  • Use of electrotherapy, acupuncture, and/or chiropractic treatments for knee OA within 4 weeks prior to Screening Visit 1 (refer to Appendix 1)
  • 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
  • Subjects requiring the chronic use (i.e., regular and consistent use for ≥ 12 weeks) of centrally acting analgesics (e.g., duloxetine) (refer to Appendix 1) within 12 weeks prior to Screening Visit 1
  • Subjects requiring the chronic use (i.e., regular and consistent use for ≥ 12 weeks) of anticonvulsants (not listed in Appendix 1) within 12 weeks prior to Screening Visit 1, unless used for seizure or migraine prophylaxis
  • Subjects requiring the usage of opioids >1x per week within 12 weeks prior to Screening Visit 1
  • Topical local anesthetic agents (gels, creams, or patches such as the Lidoderm patch) used for the treatment of knee OA within 7 days of Screening Visit 1
  • 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 Screening Visit 2 will be excluded.
  • If on NSAIDs for the treatment of OA pain, subjects who have not maintained a stable regimen in the opinion of the Investigator at Screening Visit 1
  • Any contraindications for performing DXA scans of the hips or spine including but not limited to:
  • other radiological investigations using contrast media or radionuclides within 7 days of Screening Visit 2
  • weight that precludes scanning at these sites
  • Subjects who have had a single or bilateral hip replacement
  • 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 Samumed, LLC, or any of its affiliates or development partners (that is, an employee, temporary contract worker, or designee) responsible for the conduct of the study, or who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of said employees responsible for the conduct of the study
  • Subject has non-evaluable DXA scans of the hips or spine (i.e., pins, screws, any surgical implant, fracture, or severe degenerative changes in the region of interest), as assessed by the central imaging vendor at the time of screening

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • Research Site

    Albuquerque, New Mexico, 87102

  • Research Site

    Canoga Park, California, 91303

  • Research Site

    Carmichael, California, 95628

  • Research Site

    Charleston, South Carolina, 29406

  • Research Site

    Cincinnati, Ohio, 45246

  • Research Site

    Edgewater, Florida, 32132

  • Research Site

    Kansas City, Missouri, 64114

  • Research Site

    La Mesa, California, 91941

  • Research Site

    Miami, Florida, 33143

  • Research Site

    Phoenix, Arizona, 85018

  • Research Site

    Phoenix, Arizona, 85053

  • Research Site

    San Angelo, Texas, 76904

  • Research Site

    Woodstock, Georgia, 30189

Other trials in United States

About this study

Official title: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Bone Health of Multiple Injections of SM04690 Injected in the Target Knee of Moderately to Severely Symptomatic Osteoarthritis Subjects

The primary purpose of this phase 2, placebo-controlled, double-blind, parallel group study was to provide an initial safety evaluation of two intra-articular (IA) injections of SM04690 (each at the dose of 0.07mg per 2mL injection) approximately six months apart into the target knee of moderately to severely symptomatic osteoarthritis (OA) subjects. Subjects who completed this 52-week long study were invited to enter the extension phase for an additional 52 weeks of treatment.

Read the detailed description

Study SM04690-OA-06 was a multicenter, randomized, double-blind, placebo-controlled, parallel group study of a single concentration of 0.07 mg SM04690 per 2 mL injection injected into the target knee joint of moderately to severely symptomatic OA subjects at Day 1 and Week 24 (Phase A). Subjects who completed Phase A were eligible to enter the single-blind extension phase, Phase B, for an additional 52 weeks of study treatment, receiving the randomized Phase A treatment at Week 52 and again at Week 76. The study was primarily designed to assess the safety and tolerability of repeated SM04690 injections, focusing not only on AEs but also several assessments of bone density in the knee.

Being tested
Placebo, SM04690
Keywords
SM04690, osteoarthritis, Samumed, lorecivivint, DYRK1a, CLK2
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.

  • PlaceboDrug

    Also called vehicle

    Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)

  • SM04690Drug

    Also called lorecivivint

    Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24. (In the extension phase, healthcare professional-administered intra-articular injections; first performed at Week 52 and second at Week 76.)

Study groups in NCT03727022
Study groupRoleWhat they receive
0.07 mg SM04690ExperimentalIntra-articular injections of 0.07 mg SM04690 in 2 mL vehicle
Receives: Drug: SM04690
VehiclePlacebo comparatorIntra-articular injections of 0 mg SM04690 in 2 mL vehicle
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Total BMD From Baseline in the Treated Knee Compared to Placebo by qCT

    Evaluate change in total bone mineral density (BMD) from baseline in the treated knee compared to placebo by quantitative computed tomography (qCT)

    Measured: Baseline and Week 52

Secondary outcomes (7)

  1. Change in Total BMD From Baseline in the Treated Knee Compared to Placebo by qCT

    Evaluate change in total BMD from baseline in the treated knee compared to placebo by qCT

    Measured: Baseline and Weeks 12

  2. Change in Total BMD From Baseline in the Treated Knee Compared to Placebo by qCT

    Evaluate change in total BMD from baseline in the treated knee compared to placebo by qCT

    Measured: Baseline and Week 24

  3. Change in Total BMD From Baseline in the Treated Knee Compared to Placebo by qCT

    Evaluate change in total BMD from baseline in the treated knee compared to placebo by qCT

    Measured: Baseline and Week 36

  4. Change in Total BMD From Baseline in the Treated Knee Compared to Placebo by qCT

    Evaluate change in total bone mineral density (BMD) from baseline in the treated knee compared to placebo by quantitative computed tomography (qCT)

    Measured: Baseline and Week 64

  5. Change in Total BMD From Baseline in the Treated Knee Compared to Placebo by qCT

    Evaluate change in total BMD from baseline in the treated knee compared to placebo by qCT

    Measured: Baseline and Week 76

  6. Change in Total BMD From Baseline in the Treated Knee Compared to Placebo by qCT

    Evaluate change in total BMD from baseline in the treated knee compared to placebo by qCT

    Measured: Baseline and Week 88

  7. Change in Total BMD From Baseline in the Treated Knee Compared to Placebo by qCT

    Evaluate change in total BMD from baseline in the treated knee compared to placebo by qCT

    Measured: Baseline and Week 104

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Nov 2018
  2. Study start28 Nov 2018
  3. Primary completion18 Sep 2020
  4. Study completion18 Aug 2021

Resources

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
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
101 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03727022
Sponsor's protocol ID
SM04690-OA-06
Status last verified
Jan 2026
First submitted
30 Oct 2018
Last updated
12 Jan 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing SM04690 in people with Knee Osteoarthritis, run by Biosplice Therapeutics, Inc. at 13 sites 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 18 inclusion and 41 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: finished, as of the sponsor's last update on 12 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites 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. Some participants in this study may receive a placebo. 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 12 Jan 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 in Total BMD From Baseline in the Treated Knee Compared to Placebo by qCT (time frame: Baseline and Week 52). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03727022.

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 12 Jan 2026.

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