Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 (STRIDES-X-ray)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03928184
Recruitment Status : Recruiting
First Posted : April 26, 2019
Last Update Posted : November 13, 2019
Sponsor:
Information provided by (Responsible Party):
Samumed LLC

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 Intervention/treatment Phase
Knee Osteoarthritis Drug: Lorecivivint Drug: Placebo Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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 17, 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


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
Other Name: SM04690

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




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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   40 Years 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 Screening Visit 1 (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 at Screening Visit 1 as assessed by independent central readers
  5. Radiographic disease Stage 2 or 3 in the target knee at Screening Visit 1 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 Screening Visit 1
  7. Primary source of pain throughout the body is due to OA in the target knee
  8. Body mass index (BMI) ≤ 40 kg/m2
  9. Widespread Pain Index (WPI) score of ≤ 4 and a Symptom Severity Question 2 (SSQ2) score of ≤ 2 at Screening Visit 1 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 non-target 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 < 4 in the non-target knee on the 11-point (0-10) NRS scale for the 7 days immediately preceding Day 1
  14. WOMAC Pain score of 20-40 (out of 50) 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)
  15. WOMAC Function score 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)
  16. Willingness to use an electronic diary daily in the evening for the screening period and 56-Week study duration
  17. Negative drug test for amphetamine, buprenorphine, cocaine, methadone, opiates, phencyclidine (PCP), propoxyphene, barbiturates, benzodiazepine, methaqualone, and tricyclic antidepressants, unless any of these drugs are allowed per protocol and prescribed by a physician to treat a specific condition
  18. Subjects with depression or anxiety must be clinically stable for 12 weeks prior to Screening Visit 1 and, if on treatment for depression or anxiety, be on 12 weeks of stable therapy
  19. Full understanding of the requirements of the study and willingness to comply with all study visits and assessments
  20. 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

Exclusion Criteria:

  1. Women who are pregnant, lactating, or have a positive or indeterminate pregnancy result at Screening Visit 2 or Day 1
  2. 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, but NOT tubal ligation), who are sexually active, and who are not willing to use birth control during the study period
  3. Men 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
  4. Significant malalignment of anatomical axis (medial angle formed by the femur and tibia) of the target knee (varus > 10°, valgus > 10°) by radiograph 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 Screening Visit 1
  8. Any intra-articular (IA) 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 26 weeks prior to Screening Visit 1; treatment of the target knee with IA glucocorticoids more than 12 weeks prior to Screening Visit 1 is allowed
  9. Effusion of the target knee clinically requiring aspiration within 12 weeks prior to Screening Visit 1
  10. Use of electrotherapy, acupuncture, and/or chiropractic treatments for knee OA within 4 weeks prior to Screening Visit 1
  11. Any bone fracture(s) within 26 weeks prior to Screening Visit 1
  12. Previous treatment with SM04690
  13. Subjects who have previously failed screening on this protocol and fail to meet re-screening criteria
  14. Participation in a clinical research trial that included the receipt of an investigational product (IP) or any experimental therapeutic procedure for knee OA within 26 weeks prior to Screening Visit 1, or planned participation in any such trial
  15. 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
  16. Current use, or use within 12 weeks prior to Screening Visit 1, of centrally acting analgesics
  17. Current use, or use within 12 weeks prior to Screening Visit 1, of anticonvulsants
  18. Subjects requiring the use of opioids > 1x per week within 12 weeks prior to Screening Visit 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 Screening Visit 1
  20. Any surgery scheduled during the study period. Non-surgical invasive procedures conducted for a diagnostic or therapeutic purpose scheduled during the study period are allowed
  21. 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.
  22. Clinically significant abnormal screening hematology values, blood chemistry values, or urinalysis values as determined by the Investigator
  23. 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
  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, schizoaffective disorder, major depressive disorder, or generalized anxiety 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. In addition, subjects with an HbA1c > 9 at Screening Visit 2 will be excluded.
  29. 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 Screening Visit 1
  30. Subjects who have a current or pending disability claim, workers' compensation, or litigation(s) that may compromise response to treatment
  31. 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
  32. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03928184


Contacts
Layout table for location contacts
Contact: Samumed Clinical Trials 1-855-222-0515 clinicaltrials@samumed.com

  Hide Study Locations
Locations
Layout table for location information
United States, Alabama
Research Site Recruiting
Birmingham, Alabama, United States, 35205
Research Site Recruiting
Birmingham, Alabama, United States, 35215
Research Site Recruiting
Birmingham, Alabama, United States, 35216
United States, Arizona
Research Site Recruiting
Peoria, Arizona, United States, 85381
Research Site Recruiting
Phoenix, Arizona, United States, 85037
Research Site Recruiting
Tucson, Arizona, United States, 85712
United States, Arkansas
Research Site Recruiting
Little Rock, Arkansas, United States, 72205
United States, California
Research Site Recruiting
Garden Grove, California, United States, 92840
Research Site Recruiting
Pomona, California, United States, 91767
Research Site Recruiting
San Diego, California, United States, 92103
Research Site Recruiting
San Marcos, California, United States, 92078
Research Site Recruiting
Spring Valley, California, United States, 91978
Research Site Recruiting
Westminster, California, United States, 92683
United States, Colorado
Research Site Recruiting
Boulder, Colorado, United States, 80301
Research Site Recruiting
Denver, Colorado, United States, 80209
United States, Connecticut
Research Site Recruiting
Waterbury, Connecticut, United States, 06708
United States, Florida
Research Site Recruiting
Clearwater, Florida, United States, 33761
Research Site Recruiting
Coral Gables, Florida, United States, 33134
Research Site Recruiting
Hialeah, Florida, United States, 33016
Research Site Recruiting
Miami Lakes, Florida, United States, 33014
Research Site Recruiting
Miami, Florida, United States, 33143
Research Site Recruiting
Orlando, Florida, United States, 32806
Research Site Recruiting
Oviedo, Florida, United States, 32765
Research Site Recruiting
Port Orange, Florida, United States, 32127
Research Site Recruiting
Sunrise, Florida, United States, 33351
Research Site Recruiting
West Palm Beach, Florida, United States, 33409
Research Site Recruiting
Winter Haven, Florida, United States, 33880
Research Site #1 Recruiting
Winter Park, Florida, United States, 32789
Research Site #2 Recruiting
Winter Park, Florida, United States, 32789
United States, Georgia
Research Site Recruiting
Marietta, Georgia, United States, 30060
Research Site Recruiting
Newnan, Georgia, United States, 30265
Research Site Recruiting
Stockbridge, Georgia, United States, 30281
United States, Idaho
Research Site Recruiting
Boise, Idaho, United States, 83713
Research Site Recruiting
Meridian, Idaho, United States, 83642
United States, Illinois
Research Site Recruiting
Bloomington, Illinois, United States, 61704
Research Site Recruiting
Gurnee, Illinois, United States, 60031
Research Site Recruiting
Oak Brook, Illinois, United States, 60523
Research Site Recruiting
Rockford, Illinois, United States, 61114
United States, Indiana
Research Site Recruiting
Anderson, Indiana, United States, 46011
Research Site Recruiting
Evansville, Indiana, United States, 47714
Research Site Recruiting
Valparaiso, Indiana, United States, 46383
United States, Kansas
Research Site Recruiting
Wichita, Kansas, United States, 67205
United States, Louisiana
Research Site Recruiting
Monroe, Louisiana, United States, 71203
Research Site Recruiting
New Orleans, Louisiana, United States, 70124
United States, Maryland
Research Site Recruiting
Wheaton, Maryland, United States, 20902
United States, Michigan
Research Site Recruiting
Bay City, Michigan, United States, 48706
Research Site Recruiting
Troy, Michigan, United States, 48085
United States, Missouri
Research Site Recruiting
Hazelwood, Missouri, United States, 63042
Research Site Recruiting
Saint Louis, Missouri, United States, 63141
United States, Nebraska
Research Site Recruiting
La Vista, Nebraska, United States, 68128
Research Site Recruiting
Lincoln, Nebraska, United States, 68516
Research Site Recruiting
Omaha, Nebraska, United States, 68114
United States, New Mexico
Research Site Recruiting
Albuquerque, New Mexico, United States, 87108
United States, New York
Research Site Recruiting
Great Neck, New York, United States, 11021
Research Site Recruiting
Hartsdale, New York, United States, 10530
Research Site Recruiting
New York, New York, United States, 10016
Research Site Recruiting
New York, New York, United States, 10021
Research Site Recruiting
Rochester, New York, United States, 14609
Research Site Recruiting
Williamsville, New York, United States, 14221
United States, North Carolina
Research Site Recruiting
Charlotte, North Carolina, United States, 28209
Research Site Recruiting
Leland, North Carolina, United States, 28451
Research Site Recruiting
Salisbury, North Carolina, United States, 28144
Research Site Recruiting
Winston-Salem, North Carolina, United States, 27103
United States, North Dakota
Research Site Recruiting
Fargo, North Dakota, United States, 58104
United States, Ohio
Research Site Recruiting
Cincinnati, Ohio, United States, 45219
Research Site Recruiting
Cincinnati, Ohio, United States, 45224
Research Site Recruiting
Cincinnati, Ohio, United States, 45242
Research Site Recruiting
Columbus, Ohio, United States, 43235
United States, Oklahoma
Research Site Recruiting
Oklahoma City, Oklahoma, United States, 73103
Research Site Recruiting
Oklahoma City, Oklahoma, United States, 73112
United States, Pennsylvania
Research Site Recruiting
Duncansville, Pennsylvania, United States, 16635
United States, South Carolina
Research Site Recruiting
Fort Mill, South Carolina, United States, 29707
Research Site Recruiting
Greer, South Carolina, United States, 29651
Research Site Recruiting
Mount Pleasant, South Carolina, United States, 29464
United States, South Dakota
Research Site Recruiting
Rapid City, South Dakota, United States, 57702
United States, Texas
Research Site Recruiting
Austin, Texas, United States, 78745
Research Site Recruiting
Bedford, Texas, United States, 76021
Research Site Recruiting
Carrollton, Texas, United States, 75007
Research Site Recruiting
Dallas, Texas, United States, 75231
Research Site Recruiting
Edinburg, Texas, United States, 78539
Research Site Withdrawn
Houston, Texas, United States, 77034
Research Site Recruiting
Houston, Texas, United States, 77055
Research Site Recruiting
Plano, Texas, United States, 75075
Research Site Recruiting
San Antonio, Texas, United States, 78215
Research Site Recruiting
San Antonio, Texas, United States, 78229
Research Site Recruiting
San Antonio, Texas, United States, 78258
United States, Utah
Research Site Recruiting
Draper, Utah, United States, 84020
Research Site Recruiting
Murray, Utah, United States, 84123
Research Site Recruiting
Salt Lake City, Utah, United States, 84107
United States, Virginia
Research Site Recruiting
Charlottesville, Virginia, United States, 22911
Research Site Recruiting
Richmond, Virginia, United States, 23219
Sponsors and Collaborators
Samumed LLC
Investigators
Layout table for investigator information
Study Director: Yusuf Yazici, M.D. Samumed LLC

Layout table for additonal 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: November 13, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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:
Layout table for MeSH terms
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Adavivint
Anti-Inflammatory Agents