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A Study Evaluating the Safety, Tolerability and Efficacy of Two Injections of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis

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ClinicalTrials.gov Identifier: NCT03727022
Recruitment Status : Recruiting
First Posted : November 1, 2018
Last Update Posted : September 10, 2019
Sponsor:
Information provided by (Responsible Party):
Samumed LLC

Tracking Information
First Submitted Date  ICMJE October 30, 2018
First Posted Date  ICMJE November 1, 2018
Last Update Posted Date September 10, 2019
Actual Study Start Date  ICMJE November 28, 2018
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 30, 2018)
  • Change from baseline BMD in the treated knee [ Time Frame: Baseline and Weeks 12, 24, 36 and 52 ]
    Evaluate change in bone mineral density (BMD) from baseline in the treated knee compared to placebo by quantitative computed tomography (qCT)
  • Difference in the change from baseline BMD between the treated and untreated knee [ Time Frame: Baseline and Weeks 12, 24, 36 and 52 ]
    Evaluate difference in the change in BMD from baseline between the treated and untreated knee compared to placebo by qCT
  • Change from baseline BMD of the spine and hips [ Time Frame: Baseline and Weeks 24 and 52 ]
    Evaluate change in BMD from baseline by dual-energy X-ray absorptiometry (DXA) of the spine and hips
  • Change from baseline serum bone biomarkers [ Time Frame: Baseline and Weeks 4, 12, 24, 36 and 52 ]
    Evaluate change in serum bone biomarkers (N-terminal propeptides of procollagen type I [PINP] and β-C-terminal telopeptide [β-CTX]) from baseline
  • Change from baseline serum cartilage biomarker [ Time Frame: Baseline and Weeks 4, 12, 24, 36 and 52 ]
    Evaluate change in serum cartilage biomarker (cartilage oligomeric matrix protein [COMP]) from baseline
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03727022 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 30, 2018)
  • Change from baseline OA pain in the target knee (NRS) [ Time Frame: Baseline, Weeks 1 through 52 ]
    Evaluate change from baseline OA pain in the target knee at each week as assessed by the weekly averages of subject-reported daily pain Numeric Rating Scale (NRS).
  • Change from baseline OA pain in the target knee (WOMAC pain subscore) [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 ]
    Evaluate change from baseline OA pain in the target knee as assessed by subject-reported monthly Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscore.
  • Change from baseline OA function in the target knee (WOMAC physical function subscore) [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 ]
    Evaluate change from baseline OA function in the target knee as assessed by subject-reported monthly WOMAC physical function subscore.
  • Change from baseline OA disease activity [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 ]
    Evaluate change from baseline OA disease activity as assessed by subject-reported monthly Patient Global Assessment.
  • Change from baseline in medial JSW of the target knee [ Time Frame: Baseline, Weeks 24 and 52 ]
    Evaluate change from baseline in medial joint space width (JSW) as documented by radiograph of the target knee.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Evaluating the Safety, Tolerability and Efficacy of Two Injections of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis
Official Title  ICMJE A Phase 2, 52-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of Two Injections of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects
Brief Summary The primary purpose of this phase 2, placebo-controlled, double-blind, parallel group study is to provide an initial 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. All previous studies of SM04690 have involved a single IA injection for a given subject.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Knee Osteoarthritis
Intervention  ICMJE
  • Drug: Placebo
    Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24
  • Drug: SM04690
    Healthcare professional-administered intra-articular injections; first performed on Day 1 and second at Week 24
Study Arms  ICMJE
  • Experimental: 0.07 mg SM04690
    Two intra-articular injections of 0.07 mg SM04690 in 2 mL vehicle
    Intervention: Drug: SM04690
  • Placebo Comparator: Vehicle
    Two intra-articular injections of 0 mg SM04690 in 2 mL vehicle
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 30, 2018)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2020
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Males and females between 40 and 80 years of age, inclusive, in general good health
  2. Ambulatory
  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. Pain compatible with OA of the knee(s) for at least 26 weeks prior to Screening Visit 1
  5. Primary source of pain throughout the body is due to OA in the target knee
  6. 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
  7. Pain NRS scores recorded for the target knee on at least 4 out of the 7 days immediately preceding Day 1
  8. 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
  9. Pain NRS scores recorded for the non-target knee on at least 4 out of the 7 days immediately preceding Day 1
  10. 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)
  11. Widespread Pain Index (WPI) score of ≤ 4 and a Symptom Severity Question 2 (SSQ2) score of ≤ 2 at Screening Visit 1
  12. Willingness to use an electronic diary on a daily basis in the evening for the screening period and 52-week study duration
  13. 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.
  14. 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
  15. Full understanding of the requirements of the study and willingness to comply with all study visits and assessments
  16. 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
  17. Subject's Screening Visit 1 visit must occur while enrollment into the study is open
  18. 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

Exclusion Criteria:

  1. 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
  2. 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
  3. 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
  4. Body mass index (BMI) > 35
  5. Partial or complete joint replacement in either knee
  6. Currently requires:

    1. regular use (in the opinion of the Investigator) of ambulatory assistive devices (e.g., wheelchair, parallel bars, walker, canes, or crutches), or
    2. use of a lower extremity prosthesis, and/or a structural knee brace (i.e., a knee brace that contains hardware)
  7. 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
  8. Previous enrollment in a Samumed clinical trial investigating SM04690
  9. Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to Screening Visit 1
  10. Any bone fracture(s) within 26 weeks prior to Screening Visit 1
  11. 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.
  12. Significant and clinically evident misalignment of either knee that would impact subject function, as determined by the Investigator
  13. 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
  14. Clinically significant abnormal screening hematology values, blood chemistry values, or urinalysis values as determined by the Investigator
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. Treatment of the target knee with intra-articular glucocorticoids (e.g., methylprednisolone) within 12 weeks prior to Screening Visit 1
  21. 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
  22. Treatment with systemic glucocorticoids greater than 10 mg prednisone or the equivalent per day within 4 weeks prior to Screening Visit 1
  23. Effusion of the target knee clinically requiring aspiration within 12 weeks prior to Screening Visit 1
  24. Use of electrotherapy, acupuncture, and/or chiropractic treatments for knee OA within 4 weeks prior to Screening Visit 1
  25. 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
  26. Subjects requiring the chronic use (i.e., regular and consistent use for ≥ 12 weeks) of centrally acting analgesics (e.g., duloxetine) within 12 weeks prior to Screening Visit 1
  27. Subjects requiring the chronic use (i.e., regular and consistent use for ≥ 12 weeks) of anticonvulsants (not listed in the study protocol) within 12 weeks prior to Screening Visit 1, unless used for seizure or migraine prophylaxis
  28. Subjects requiring the usage of opioids >1x per week within 12 weeks prior to Screening Visit 1
  29. 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
  30. 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.
  31. 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
  32. Any contraindications for performing DXA scans of the hips or spine including but not limited to:

    1. other radiological investigations using contrast media or radionuclides within 7 days of Screening Visit 2
    2. weight that precludes scanning at these sites
  33. Subjects who have had a single or bilateral hip replacement
  34. Subjects who have a current or pending disability claim, workers' compensation, or litigation(s) that may compromise response to treatment
  35. 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
  36. 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
  37. 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Samumed Clinical Trials 1-855-222-0515 clinicaltrials@samumed.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03727022
Other Study ID Numbers  ICMJE SM04690-OA-06
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Samumed LLC
Study Sponsor  ICMJE Samumed LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Yusuf Yazici, M.D. Samumed LLC
PRS Account Samumed LLC
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP