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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/20/2021.

A Study Utilizing Patient-Reported and Radiographic Outcomes and Evaluating the Safety and Efficacy of Lorecivivint (SM04690) for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis

Clinicaltrials.gov identifier NCT03928184

Recruitment Status Active, not recruiting

First Posted April 26, 2019

Last update posted September 3, 2020

Study Description

Brief summary:

This phase 3 study is a multicenter, randomized, double-blind, placebo-controlled study of lorecivivint injected intra-articularly (IA) into the target knee (most painful) joint of moderately to severely symptomatic osteoarthritis (OA) subjects at a single dose of 0.07 mg lorecivivint per 2 mL injection. This study will utilize radiographs and patient reported outcomes (PROs) to evaluate the safety and efficacy of lorecivivint.

  • Condition or Disease:Knee Osteoarthritis
  • Intervention/Treatment: Drug: Lorecivivint
    Drug: Placebo
  • Phase: Phase 3
Detailed Description

N/A

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 725 participants
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: Triple (Participant, Investigator, Outcomes Assessor)
  • Primary Purpose: Treatment
  • Official Title: A Phase 3, 56-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Utilizing Patient-Reported and Radiographic Outcomes to Evaluate the Efficacy and Safety of a Single Injection of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects
  • Actual Study Start Date: May 2019
  • Estimated Primary Completion Date: June 2021
  • Estimated Study Completion Date: June 2021
Arms and interventions
Arm Intervention/treatment
Experimental: 0.07 mg lorecivivint
One intra-articular injection of 0.07 mg lorecivivint in 2 ml vehicle
Drug: Lorecivivint
Healthcare professional-administered intra-articular injection; performed on Day 1
Placebo Comparator: Vehicle
One intra-articular injection of 0 mg lorecivivint in 2 ml vehicle
Drug: Placebo
Healthcare professional-administered intra-articular injection; performed on Day 1
Outcome Measures
  • Primary Outcome Measures: 1. Change from baseline in OA pain in the target knee (pain NRS) [ Time Frame: Baseline and Week 12 ]
    Evaluate change from baseline OA pain in the target knee as assessed by the weekly averages of daily pain numeric rating scale (NRS). 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.
  • Secondary Outcome Measures: 1. Change from baseline in OA pain in the target knee (Pain NRS) [ Time Frame: Baseline, Weeks 24 and 52 ]
    Evaluate change from baseline OA pain in the target knee as assessed by the weekly averages of daily pain Numeric Rating Scale (NRS). 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.
  • 2. Change from baseline in OA function in the target knee (WOMAC Function) [ Time Frame: Baseline, Weeks 12, 24 and 52 ]
    Evaluate change from baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function subscore (WOMAC Function). The WOMAC is a widely-used, proprietary outcome measurement tool used 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 4 (highest pain/highest stiffness/lowest function). The WOMAC Function subscore ranges from 0 to 68.
  • 3. Change from baseline in OA disease activity (Patient Global Assessment) [ Time Frame: Baseline, Weeks 12, 24 and 52 ]
    Evaluate change from baseline OA disease activity as assessed by Patient Global Assessment. The Patient Global Assessment is an 11-point [0-10] Numeric Rating Scale [NRS] on which the subjects will rate how they feel their target knee OA is doing, considering all the ways in which their target knee OA may affect them. The NRS is anchored by descriptors at each end ("Very Good" on the left and "Very Bad" on the right).
  • 4. Change from baseline in usage of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen for target knee OA pain [ Time Frame: Baseline and Week 52 ]
  • Other Outcome Measures: 1. Change from baseline in serum bone biomarkers [ Time Frame: Baseline and Week 56 ]
    Evaluate change from baseline in serum bone biomarkers N-terminal propeptides of procollagen type I [PINP] and β-C-terminal telopeptide [β-CTX]
  • 2. Change from baseline in a serum cartilage biomarker [ Time Frame: Baseline and Week 56 ]
    Evaluate change from baseline in serum cartilage biomarker cartilage oligomeric matrix protein [COMP]
  • 3. Change from baseline in medial joint space width (mJSW) in the target knee [ Time Frame: Baseline and Week 52 ]
    Evaluate change from baseline in mJSW as documented by radiograph of the target knee
  • 4. Change from baseline in health-related quality of life (HRQOL) [ Time Frame: Baseline and Week 52 ]
    Evaluate change from baseline in HRQOL as assessed by the 36-Item Short Form Health Survey (SF-36). The SF-36 consists of eight scaled scores which are the weighted sums of the questions in their section (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health). Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. A score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
  • 5. Change from baseline in OA pain in the target knee (WOMAC Pain) [ Time Frame: Baseline, Weeks 12, 24 and 52 ]
    Evaluate change from baseline in OA pain in the target knee as assessed by WOMAC pain subscore (WOMAC Pain). The WOMAC is a widely-used, proprietary outcome measurement tool used 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 4 (highest pain/highest stiffness/lowest function). The WOMAC Pain subscore ranges from 0 to 20.
  • 6. Change from baseline in OA pain, function and stiffness (WOMAC Total score) [ Time Frame: Baseline, Weeks 12, 24 and 52 ]
    Evaluate change from baseline in OA pain, function and stiffness as a composite outcome measure as assessed by WOMAC Total score. The WOMAC is a widely-used, proprietary outcome measurement tool used 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 4 (highest pain/highest stiffness/lowest function). WOMAC Total is a composite of the three domains (pain/stiffness/function) with a total score of 0 to 96.
Eligibility Criteria
  • Ages Eligible for Study: 40 to 80 Years (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

1. Males and females between 40 and 80 years of age, inclusive, in general good health
apart from their knee OA

2. Ambulatory (single assistive devices such as canes allowed if needed less than 50% of
the time, subjects requiring a walker are excluded)

3. 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)

4. mJSW by radiograph between 1.5 and 4 mm, inclusive, in the target knee within 12 weeks
of the Screening Visit as assessed by independent central readers

5. Radiographic disease Stage 2 or 3 in the target knee within 12 weeks of the Screening
Visit according to the Kellgren-Lawrence (KL) grading of knee OA as assessed by
independent central readers

6. Pain compatible with OA of the knee(s) for at least 26 weeks prior to the Screening
Visit

7. Primary source of pain throughout the body is due to OA in the target knee

8. Body mass index (BMI) ≤ 40 kg/m2 at the Screening Visit

9. Widespread Pain Index (WPI) score of ≤ 4 and a Symptom Severity Question 2 (SSQ2)
score of ≤ 2 at the Screening Visit and Day 1

10. Pain NRS scores recorded for the target knee on at least 4 out of the 7 days
immediately preceding Day 1

11. Pain NRS scores recorded for the nontarget knee on at least 4 out of the 7 days
immediately preceding Day 1

12. 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

13. Daily OA knee pain diary average NRS intensity score 10°, valgus > 10°) by radiograph within 12 weeks of
the Screening Visit as assessed by independent central readers

5. Partial or complete joint replacement in either knee

6. Currently requires use of a lower extremity prosthesis, and/or a structural knee brace
(i.e., a knee brace that contains hardware)

7. Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to Day 1

8. Intra-articular (IA) injection into the target knee with a therapeutic aim including,
but not limited to, hyaluronic acid, platelet-rich plasma (PRP),and stem cell
therapies within 26 weeks prior to Day 1, or IA glucocorticoids within 12 weeks prior
to Day 1

9. Effusion of the target knee clinically requiring aspiration within 12 weeks prior to
Day 1

10. Use of electrotherapy, acupuncture, physical therapy, therapeutic ultrasound, and/or
chiropractic treatments for knee OA within 4 weeks prior to Day 1

11. Any bone fracture(s) within 26 weeks prior to the Screening Visit

12. Previous treatment with SM04690

13. Subjects who have previously failed screening on this protocol and fail to meet
rescreening criteria

14. 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 the Screening Visit, or planned participation in any such trial

15. Treatment with systemic (oral, intramuscular, or intravenous) glucocorticoids ≥10 mg
prednisone or the equivalent per day within 4 weeks prior to Day 1, or subjects on 1x per week within 12 weeks prior to Day 1

19. Topical local anesthetic agents (gels, creams, or patches such as the Lidoderm patch)
used for the treatment of knee OA within 7 days of Day 1

20. Planned surgery scheduled during the study period, not including non-surgical invasive
procedures conducted for a diagnostic or therapeutic purpose scheduled during the
study period

21. History of malignancy within the last 5 years, not including subjects with prior
history of adequately treated in situ cervical cancer or basal or squamous cell skin
cancer

22. Clinically significant abnormal screening hematology values, blood chemistry values,
or urinalysis values as determined by the Investigator

23. 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

24. 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

25. 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

26. History of mania, bipolar disorder, psychotic disorder, schizophrenia, or
schizoaffective disorder

27. Any known active infections, including urinary tract infection, upper respiratory
tract infection, sinusitis, suspicion of IA 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

28. 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.

29. Hemoglobin A1c (HbA1c) >9 at the Screening Visit

30. If using NSAIDs and/or acetaminophen, subjects who have not maintained a stable
regimen in the opinion of the Investigator for at least 4 weeks prior to Day 1

31. Any contraindications for an IA injection in the target knee in the opinion of the
Investigator

32. Subjects who have a current or pending disability claim, workers' compensation, or
litigation(s) that may compromise response to treatment

33. 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

34. 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

Contacts and Locations
Contacts
Locations
Show 98 Study Locations
Sponsors and Collaborators

Samumed LLC

Investigators

Study Director: Yusuf Yazici, M.D. Samumed LLC

More Information
  • Responsible Party: Samumed LLC
  • ClinicalTrials.gov Identifier: NCT03928184 History of Changes
  • Other Study ID Numbers: SM04690-OA-11
  • First Posted: April 26, 2019 Key Record Dates
  • Last Update Posted: September 3, 2020
  • Last Verified: September 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: No
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Samumed LLC: SM04690
    Wnt pathway inhibitor
    osteoarthritis
    Samumed
    lorecivivint
  • Additional relevant MeSH terms: Osteoarthritis Osteoarthritis, Knee