Knee OsteoarthritisPhase 2NCT03122860

A Study Evaluating the Safety and Efficacy 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 74 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

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: 700 participants
Where: 74 sitesUnited States
Study dates: 24 Apr 2017to 30 Apr 2018
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
Diagnosis of femorotibial OA in the target knee by standard American College of Rheumatology (ACR) criteria at screening (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
Primary source of pain throughout the body is due to OA in the target knee
Willingness to use an electronic diary on a daily basis in the evening for the screening period and 24-week study duration
Negative drug test for opioids and drugs of abuse, except alcohol and marijuana, at screening

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Subjects with depression or anxiety must be clinically stable for 12 weeks prior to screening, 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

Who cannot join

Women who are pregnant, lactating, or have a positive pregnancy result at screening
Women of child bearing potential who are sexually active and are not willing to use a highly effective method of birth control 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 whom are not using a highly effective method of birth control
Body mass index (BMI) > 35
Partial or complete joint replacement in either knee
Currently requires regular use 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

Show all 23Show fewer

Previous participation in a Samumed clinical trial investigating SM04690
Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to screening
Any planned surgery during the study period
History of malignancy within the last 5 years; however, subjects with prior history of in situ cancer or 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 any study injection
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
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 any study injection, 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
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; treatment of the target knee with intra-articular glucocorticoids greater than 12 weeks prior to screening is allowed
Treatment with systemic glucocorticoids greater than 10 mg prednisone or the equivalent per day within 4 weeks prior to screening
Effusion of the target knee clinically requiring aspiration within 12 weeks prior to screening
Use of electrotherapy, acupuncture, and/or chiropractic treatments for knee OA within 4 weeks prior to screening
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 study start
Use of centrally acting analgesics (e.g., duloxetine) within 12 weeks prior to screening
Use of anticonvulsants within 12 weeks prior to screening, unless used for seizure or migraine prophylaxis
Subjects requiring the usage of opioids >1x per week within 12 weeks prior to screening
Use of topical local anesthetic agents (gels, creams, or patches such as the Lidoderm patch) for the treatment of knee OA within 7 days of screening

Trial locations and contacts

74 sites in 1 country.

City, postcode or hospital

74 sites in 1 country

United States74 sites

Research Site
Albuquerque, New Mexico, 87102
Research Site
Anaheim, California, 92801
Research Site
Anniston, Alabama, 36207
Research Site
Arlington, Virginia, 22207
Research Site
Austin, Texas, 78745
Research Site
Bedford, Texas, 76021
Research Site
Birmingham, Alabama, 35216
Research Site
Boston, Massachusetts, 02111
Research Site
Boulder, Colorado, 80301
Research Site
Canoga Park, California, 91303
Research Site
Carmichael, California, 95608
Research Site
Cerritos, California, 90703
Research Site
Chandler, Arizona, 85224
Research Site
Charleston, South Carolina, 29406
Research Site
Charlotte, North Carolina, 28209
Research Site
Charlotte, North Carolina, 28210
Research Site
Charlottesville, Virginia, 22911
Research Site
Chicago, Illinois, 60607
Research Site
Cincinnati, Ohio, 45224
Research Site
Cincinnati, Ohio, 45246
Research Site
City of Saint Peters, Missouri, 63303
Research Site
Clearwater, Florida, 33761
Research Site
Cleveland, Ohio, 44122
Research Site
Columbus, Ohio, 43213
Research Site
Coral Gables, Florida, 33134
Research Site
Dallas, Texas, 75231
Research Site
Danville, Virginia, 24541
Research Site
DeLand, Florida, 32720
Research Site
Duncansville, Pennsylvania, 16635
Research Site
Edgewater, Florida, 32132
Research Site
El Cajon, California, 92020
Research Site
Evansville, Indiana, 47714
Research Site
Fargo, North Dakota, 58103
Research Site
Frederick, Maryland, 21702
Research Site
Gold River, California, 95670
Research Site
High Point, North Carolina, 27262
Research Site
Houston, Texas, 77055
Research Site
Jefferson, Louisiana, 70121
Research Site
Kansas City, Missouri, 64114
Research Site
La Mesa, California, 91942
Research Site
Las Vegas, Nevada, 89119
Research Site
Lauderdale Lakes, Florida, 33319
Research Site
Lexington, Kentucky, 40504
Research Site
Lincoln, Nebraska, 68516
Research Site
Los Angeles, California, 90036
Research Site
Marietta, Georgia, 30060
Research Site
Miami, Florida, 33143
Research Site
Mobile, Alabama, 36608
Research Site
Mt. Pleasant, South Carolina, 29464
Research Site
Newton, Kansas, 67114
Research Site
Philadelphia, Pennsylvania, 19152
Research Site
Phoenix, Arizona, 85018
Research Site
Phoenix, Arizona, 85053
Research Site
Pinellas Park, Florida, 33781
Research Site
Prairie Village, Kansas, 66208
Research Site
Rancho Mirage, California, 92270
Research Site
Rapid City, South Dakota, 57702
Research Site
Rochester, New York, 14609
Research Site
Sacramento, California, 95817
Research Site
Salisbury, North Carolina, 28144
Research Site
San Angelo, Texas, 76904
Research Site
San Diego, California, 92103
Research Site
San Marcos, California, 92078
Research Site
Spring Valley, California, 91978
Research Site
St Louis, Missouri, 63141
Research Site
Stamford, Connecticut, 06905
Research Site
State College, Pennsylvania, 16801
Research Site
Troy, Michigan, 48085
Research Site
Trumbull, Connecticut, 06606
Research Site
Tucson, Arizona, 85712
Research Site
Waterbury, Connecticut, 06708
Research Site
Wichita, Kansas, 67205
Research Site
Wilmington, North Carolina, 28401
Research Site
Woodstock, Georgia, 30189

Other trials in United States

About this study

Official title: A Phase 2, 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis

This phase 2 study is a placebo-controlled, double-blind, parallel group study of four concentrations of SM04690 (0.03, 0.07, 0.15, and 0.23 mg per 2 mL injection) injected intraarticularly (IA) into the target knee joint of subjects with moderately to severely symptomatic osteoarthritis (OA). Based on previous studies of SM04690, key phenotypes of laterality (unilateral vs bilateral) as well as chronic pain (as measured by the Widespread Pain Index) were identified as confounding variables impacting the overall assessment of both radiologic and clinical efficacy outcomes. The design of SM04690-OA-04 is based upon previous study designs while assessing strategies to combat the confounding impact of laterality and chronic pain. To evaluate the effect of IA vehicle injection on patient-reported outcomes (PRO) such as pain, stiffness, and function in OA, this study also includes one cohort that receives a 2 mL IA injection of vehicle (placebo), and one cohort that receives a sham injection (i.e., a needle stick with 0 mL vehicle injected).

Conditions: Knee Osteoarthritis
Being tested: SM04690, Placebo, Sham
Keywords: SM04690, Wnt pathway inhibitor, osteoarthritis, Samumed
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.

SM04690Drug
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study
PlaceboOther
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study
ShamOther
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study

Study groups in NCT03122860
Study group	Role	What they receive
0.03 mg SM04690	Experimental	Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle Receives: Drug: SM04690
0.07 mg SM04690	Experimental	Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle Receives: Drug: SM04690
0.15 mg SM04690	Experimental	Single intra-articular injection of 0.15 mg SM04690 in 2 mL vehicle Receives: Drug: SM04690
0.23 mg SM04690	Experimental	Single intra-articular injection of 0.23 mg SM04690 in 2 mL vehicle Receives: Drug: SM04690
Placebo	Placebo comparator	Single intra-articular injection of 0 mg SM04690 in 2 mL vehicle Receives: Other: Placebo
Sham	Sham comparator	Single intra-articular injection of 0 mg SM04690 in 0 mL vehicle Receives: Other: Sham

What is being measured

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

Change From Baseline Osteoarthritis (OA) Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS)
Change from baseline OA pain in the target knee as assessed by the weekly average of daily pain NRS at Week 24. 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 (pain as bad as one can imagine).
Measured: Baseline and Week 24
Change From Baseline OA Pain in the Target Knee as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain)
Change from baseline OA pain in the target knee as assessed by WOMAC Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain) at Week 24. 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 is standardized and reported ranging from 0 to 100 [0 = no pain; 100 = pain as bad as it can be].
Measured: Baseline and Week 24
Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function)
Change from baseline OA function in the target knee as assessed by WOMAC Numeric Rating Scale (NRS 3.1) physical functioning subscore (WOMAC Function) at Week 24. 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 is standardized and reported ranging from 0 to 100 [0 = no functional disability, 100 = unable to function].
Measured: Baseline and Week 24
Change From Baseline in Medial Joint Space Width (mJSW) of the Target Knee
Change from baseline in mJSW as documented by radiograph of the target knee.
Measured: Baseline and Week 24

Secondary outcomes (1)

Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA)
Change from baseline OA disease activity as assessed by PtGA at Week 24. The PtGA was completed using a 100 mm visual analog scale (VAS) adapted from the Patient Assessment Form © 1999, American College of Rheumatology. The subject rated how well he/she was doing, considering all the ways in which illness and health conditions may affected him/her. The VAS scale was anchored by "Very Well" on the left (scored as 0) and "Very Poorly" on the right (scored as 100). Higher scores indicated poorer disease assessment by the subject.
Measured: Baseline and Week 24

Timeline

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

24 Apr 201730 Apr 2018

First posted21 Apr 2017
Study start24 Apr 2017
Primary completion30 Apr 2018
Study completion30 Apr 2018

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.
Publications (4)Papers the sponsor has linked to this study.
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: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 700 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03122860
Sponsor's protocol ID: SM04690-OA-04
Status last verified: May 2021
First submitted: 18 Apr 2017
Last updated: 11 Jun 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Yazici Y, McAlindon TE, Gibofsky A, Lane NE, Lattermann C, Skrepnik N, Swearingen CJ, Simsek I, Ghandehari H, DiFrancesco A, Gibbs J, Tambiah JRS, Hochberg MC. A Phase 2b randomized trial of lorecivivint, a novel intra-articular CLK2/DYRK1A inhibitor and Wnt pathway modulator for knee osteoarthritis. Osteoarthritis Cartilage. 2021 May;29(5):654-666. doi: 10.1016/j.joca.2021.02.004. Epub 2021 Feb 12.
PubMed 33588087
Tambiah J, Kennedy S, Swearingen C, McAlindon T, Yazici Y. Impact of structural severity on outcomes in knee osteoarthritis: an analysis of data from phase 2 and phase 3 lorecivivint clinical trials. Rheumatology (Oxford). 2025 May 1;64(5):2583-2590. doi: 10.1093/rheumatology/keae610.
PubMed 39495154
Tambiah JRS, Simsek I, Swearingen CJ, Kennedy S, Cole BJ, McAlindon TE, Yazici Y. Comparing Patient-Reported Outcomes From Sham and Saline-Based Placebo Injections for Knee Osteoarthritis: Data From a Randomized Clinical Trial of Lorecivivint. Am J Sports Med. 2022 Mar;50(3):630-636. doi: 10.1177/03635465211067201. Epub 2022 Jan 10.
PubMed 35005990
Tambiah JRS, Kennedy S, Swearingen CJ, Simsek I, Yazici Y, Farr J, Conaghan PG. Individual Participant Symptom Responses to Intra-Articular Lorecivivint in Knee Osteoarthritis: Post Hoc Analysis of a Phase 2B Trial. Rheumatol Ther. 2021 Jun;8(2):973-985. doi: 10.1007/s40744-021-00316-w. Epub 2021 Jun 8.
PubMed 34101138

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 11 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis
ClinicalTrials.gov ID: NCT03122860
Acronym / sponsor ID: SM04690-OA-04
Conditions: Knee Osteoarthritis
Keywords: SM04690, Wnt pathway inhibitor, osteoarthritis, Samumed
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 700 participants (actual)
Lead sponsor: Biosplice Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 24 Apr 2017 (actual)
Primary completion: 30 Apr 2018 (actual)
Study completion: 30 Apr 2018 (actual)
First posted: 21 Apr 2017 (actual)
Results: Posted 18 May 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 6

Arm	Type	Receives
0.03 mg SM04690	Experimental	Drug: SM04690Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle
0.07 mg SM04690	Experimental	Drug: SM04690Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle
0.15 mg SM04690	Experimental	Drug: SM04690Single intra-articular injection of 0.15 mg SM04690 in 2 mL vehicle
0.23 mg SM04690	Experimental	Drug: SM04690Single intra-articular injection of 0.23 mg SM04690 in 2 mL vehicle
Placebo	Placebo comparator	Other: PlaceboSingle intra-articular injection of 0 mg SM04690 in 2 mL vehicle
Sham	Sham comparator	Other: ShamSingle intra-articular injection of 0 mg SM04690 in 0 mL vehicle

Who may qualify

Ages: 40 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Ambulatory
Diagnosis of femorotibial OA in the target knee by standard American College of Rheumatology (ACR) criteria at screening (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
Primary source of pain throughout the body is due to OA in the target knee
Willingness to use an electronic diary on a daily basis in the evening for the screening period and 24-week study duration

Key exclusion criteria (23 listed)

Women who are pregnant, lactating, or have a positive pregnancy result at screening
Women of child bearing potential who are sexually active and are not willing to use a highly effective method of birth control 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 whom are not using a highly effective method of birth control
Body mass index (BMI) > 35
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
SM04690Healthcare professional-administered intra-articular injection performed once on Day 1 of the study	Drug	0.03 mg SM04690, 0.07 mg SM04690, 0.15 mg SM04690, 0.23 mg SM04690
PlaceboHealthcare professional-administered intra-articular injection performed once on Day 1 of the study	Other	Placebo
ShamHealthcare professional-administered intra-articular injection performed once on Day 1 of the study	Other	Sham

Primary outcome

Change From Baseline Osteoarthritis (OA) Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS)
Time frame: Baseline and Week 24
Change from baseline OA pain in the target knee as assessed by the weekly average of daily pain NRS at Week 24. 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 (pain as bad as one can imagine).
Change From Baseline OA Pain in the Target Knee as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain)
Time frame: Baseline and Week 24
Change from baseline OA pain in the target knee as assessed by WOMAC Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain) at Week 24. 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 is standardized and reported ranging from 0 to 100 [0 = no pain; 100 = pain as bad as it can be].
Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function)
Time frame: Baseline and Week 24
Change from baseline OA function in the target knee as assessed by WOMAC Numeric Rating Scale (NRS 3.1) physical functioning subscore (WOMAC Function) at Week 24. 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 is standardized and reported ranging from 0 to 100 [0 = no functional disability, 100 = unable to function].
Change From Baseline in Medial Joint Space Width (mJSW) of the Target Knee
Time frame: Baseline and Week 24
Change from baseline in mJSW as documented by radiograph of the target knee.

1 secondary outcome

Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA)
Time frame: Baseline and Week 24

Results and safety

Results posted to the registry on 18 May 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
0.03 mg SM04690	117	107
0.07 mg SM04690	116	111
0.15 mg SM04690	117	105
0.23 mg SM04690	116	105
Placebo	117	102
Sham	117	105

Primary outcome: Change From Baseline Osteoarthritis (OA) Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS)

Time frame: Baseline and Week 24. Mean (Standard Deviation). Unit: score on a scale

Measure	0.03 mg SM04690 n = 98	0.07 mg SM04690 n = 102	0.15 mg SM04690 n = 92	0.23 mg SM04690 n = 90	Placebo n = 95	Sham n = 91
Value	-2.77 (2.44)	-2.93 (2.21)	-2.43 (2.18)	-3.03 (2.43)	-2.26 (2.44)	-2.21 (2.46)

0.03 mg SM04690 vs Placebo: Median Difference (Final Values): -0.46 (95% CI -1.13 to 0.21), p = 0.179, ANCOVA
0.07 mg SM04690 vs Placebo: Median Difference (Final Values): -0.70 (95% CI -1.34 to -0.06), p = 0.031, ANCOVA
0.15 mg SM04690 vs Placebo: Mean Difference (Final Values): -0.14 (95% CI -0.81 to 0.52), p = 0.675, ANCOVA

Population analysed: Data is reported as observed with no imputation. Discrepancy between the number of participants analyzed and the number of participants assigned to the arms is the result of missing data and/or subject withdrawal.

Primary outcome: Change From Baseline OA Pain in the Target Knee as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain)

Time frame: Baseline and Week 24. Mean (Standard Error). Unit: score on a scale

Measure	0.03 mg SM04690 n = 94	0.07 mg SM04690 n = 102	0.15 mg SM04690 n = 93	0.23 mg SM04690 n = 93	Placebo n = 93	Sham n = 92
Value	-27.6 (22.8)	-30.0 (22.5)	-24.7 (21.6)	-33.3 (22.9)	-25.5 (25.8)	-22.5 (24.6)

0.03 mg SM04690 vs Placebo: Mean Difference (Final Values): -1.70 (95% CI -8.32 to 4.91), p = 0.612, ANCOVA
0.07 mg SM04690 vs Placebo: Mean Difference (Final Values): -4.01 (95% CI -10.47 to 2.46), p = 0.223, ANCOVA
0.15 mg SM04690 vs Placebo: Mean Difference (Final Values): 1.84 (95% CI -4.89 to 8.57), p = 0.590, ANCOVA

Primary outcome: Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function)

Time frame: Baseline and Week 24. Mean (Standard Deviation). Unit: score on a scale

Measure	0.03 mg SM04690 n = 94	0.07 mg SM04690 n = 102	0.15 mg SM04690 n = 93	0.23 mg SM04690 n = 93	Placebo n = 93	Sham n = 92
Value	-27.7 (21.1)	-29.3 (23.0)	-23.6 (21.6)	-32.4 (22.1)	-24.9 (23.7)	-23.8 (23.7)

0.03 mg SM04690 vs Placebo: Mean Difference (Final Values): -2.58 (95% CI -9.04 to 3.88), p = 0.432, ANCOVA
0.07 mg SM04690 vs Placebo: Mean Difference (Final Values): -4.34 (95% CI -10.69 to 2.02), p = 0.180, ANCOVA
0.15 mg SM04690 vs Placebo: Mean Difference (Final Values): 1.19 (95% CI -5.33 to 7.72), p = 0.718, ANCOVA

Primary outcome: Change From Baseline in Medial Joint Space Width (mJSW) of the Target Knee

Time frame: Baseline and Week 24. Mean (Standard Deviation). Unit: mm

Measure	0.03 mg SM04690 n = 104	0.07 mg SM04690 n = 109	0.15 mg SM04690 n = 103	0.23 mg SM04690 n = 101	Placebo n = 96	Sham n = 104
Value	0.02 (0.72)	-0.11 (0.53)	-0.11 (0.92)	-0.03 (0.45)	-0.01 (0.60)	-0.08 (0.58)

0.03 mg SM04690 vs Placebo: Mean Difference (Final Values): 0.02 (95% CI -0.16 to 0.21), p = 0.822, ANCOVA
0.07 mg SM04690 vs Placebo: Mean Difference (Final Values): -0.11 (95% CI -0.27 to 0.04), p = 0.162, ANCOVA
0.15 mg SM04690 vs Placebo: Mean Difference (Final Values): -0.12 (95% CI -0.34 to 0.09), p = 0.267, ANCOVA

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Data regarding treatment-emergent adverse events (TEAEs) was collected in this study. TEAEs are events that occur during the course of the study that are not present prior to Day 1 study medication injection, or, if present at the time of study medication injection, have worsened in severity during the course of the study. TEAEs were assessed at each study visit from the time of study medication injection on study visit Day 1 through Week 24 (End-of-Study)/Early Termination.. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
0.03 mg SM04690	2 of 106 (1.9%)	14 of 106 (13.2%)	0 of 106
0.07 mg SM04690	0 of 104 (0%)	19 of 104 (18.3%)	0 of 104
0.15 mg SM04690	0 of 106 (0%)	14 of 106 (13.2%)	0 of 106
0.23 mg SM04690	2 of 106 (1.9%)	17 of 106 (16%)	0 of 106
Placebo	1 of 114 (0.9%)	15 of 114 (13.2%)	0 of 114
Sham	0 of 120 (0%)	22 of 120 (18.3%)	0 of 120
Other	1 of 39 (2.6%)	9 of 39 (23.1%)	0 of 39

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 33588087Yazici Y, McAlindon TE, Gibofsky A, Lane NE, Lattermann C, Skrepnik N, Swearingen CJ, Simsek I, Ghandehari H, DiFrancesco A, Gibbs J, Tambiah JRS, Hochberg MC. A Phase 2b randomized trial of lorecivivint, a novel intra-articular CLK2/DYRK1A inhibitor and Wnt pathway modulator for knee osteoarthritis. Osteoarthritis Cartilage. 2021 May;29(5):654-666. doi: 10.1016/j.joca.2021.02.004. Epub 2021 Feb 12.
Derived from this study: PubMed 39495154Tambiah J, Kennedy S, Swearingen C, McAlindon T, Yazici Y. Impact of structural severity on outcomes in knee osteoarthritis: an analysis of data from phase 2 and phase 3 lorecivivint clinical trials. Rheumatology (Oxford). 2025 May 1;64(5):2583-2590. doi: 10.1093/rheumatology/keae610.
Derived from this study: PubMed 35005990Tambiah JRS, Simsek I, Swearingen CJ, Kennedy S, Cole BJ, McAlindon TE, Yazici Y. Comparing Patient-Reported Outcomes From Sham and Saline-Based Placebo Injections for Knee Osteoarthritis: Data From a Randomized Clinical Trial of Lorecivivint. Am J Sports Med. 2022 Mar;50(3):630-636. doi: 10.1177/03635465211067201. Epub 2022 Jan 10.
Derived from this study: PubMed 34101138Tambiah JRS, Kennedy S, Swearingen CJ, Simsek I, Yazici Y, Farr J, Conaghan PG. Individual Participant Symptom Responses to Intra-Articular Lorecivivint in Knee Osteoarthritis: Post Hoc Analysis of a Phase 2B Trial. Rheumatol Ther. 2021 Jun;8(2):973-985. doi: 10.1007/s40744-021-00316-w. Epub 2021 Jun 8.
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.

74 sites in 1 country: see every site and its status.

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 74 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 9 inclusion and 23 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 11 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 74 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 18 May 2021). 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 Osteoarthritis (OA) Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS) (time frame: Baseline and Week 24). 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?

On the ClinicalTrials.gov record for NCT03122860, which also lists 4 linked publications.

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 11 Jun 2021.