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

NCT03727022 | Completed Phase 2 Results FDA Drug

• 1 other identifier: SM04690-OA-06
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 13

Brief 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 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.

Conditions

Knee Osteoarthritis

Keywords

SM04690; osteoarthritis; Samumed; lorecivivint; DYRK1a; CLK2

Outcome Measures

Primary Outcomes (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)

  Baseline and Week 52

Secondary Outcomes (7)

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

  Baseline and Weeks 12

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

  Baseline and Week 24

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

  Baseline and Week 36

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

  Baseline and Week 64

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

  Baseline and Week 76

Study Arms (2)

0.07 mg SM04690

EXPERIMENTAL

Intra-articular injections of 0.07 mg SM04690 in 2 mL vehicle

Drug: SM04690

Vehicle

PLACEBO COMPARATOR

Intra-articular injections of 0 mg SM04690 in 2 mL vehicle

Drug: Placebo

Interventions

Placebo DRUG

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.)

Also known as: vehicle

Vehicle

SM04690 DRUG

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.)

Also known as: lorecivivint

0.07 mg SM04690

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• Biosplice Therapeutics, Inc.: lead

Study Sites (13)

Research Site

Phoenix, Arizona, 85018, United States

Location

Research Site

Phoenix, Arizona, 85053, United States

Location

Research Site

Canoga Park, California, 91303, United States

Location

Research Site

Carmichael, California, 95628, United States

Location

Research Site

La Mesa, California, 91941, United States

Location

Research Site

Edgewater, Florida, 32132, United States

Location

Research Site

Miami, Florida, 33143, United States

Location

Research Site

Woodstock, Georgia, 30189, United States

Location

Research Site

Kansas City, Missouri, 64114, United States

Location

Research Site

Albuquerque, New Mexico, 87102, United States

Location

Research Site

Cincinnati, Ohio, 45246, United States

Location

Research Site

Charleston, South Carolina, 29406, United States

Location

Research Site

San Angelo, Texas, 76904, United States

Location

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Interventions

lorecivivint

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Results Point of Contact

• Title: Christopher Swearingen, PhD, VP of Biometrics
• Organization: Biosplice Therapeutics

info@biosplice.com

858.926.2900

Study Officials

• Yusuf Yazici, M.D.

  Biosplice Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2018
• First Posted: November 1, 2018
• Study Start: November 28, 2018
• Primary Completion: September 18, 2020
• Study Completion: August 18, 2021
• Last Updated: January 12, 2026
• Results First Posted: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)