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

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ClinicalTrials.gov Identifier: NCT03122860
Recruitment Status : Completed
First Posted : April 21, 2017
Last Update Posted : August 15, 2018
Sponsor:
Information provided by (Responsible Party):
Samumed LLC

Brief Summary:
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 will also include two placebo cohorts-one cohort that receives a 2 mL IA injection of vehicle, and one cohort that receives a sham injection (i.e., a needle stick with 0 mL vehicle injected).

Condition or disease Intervention/treatment Phase
Knee Osteoarthritis Drug: SM04690 Drug: placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 700 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : April 24, 2017
Actual Primary Completion Date : April 30, 2018
Actual Study Completion Date : April 30, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Arm Intervention/treatment
Experimental: 0.03 mg SM04690
Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle
Drug: SM04690
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study

Experimental: 0.07 mg SM04690
Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle
Drug: SM04690
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study

Experimental: 0.15 mg SM04690
Single intra-articular injection of 0.15 mg SM04690 in 2 mL vehicle
Drug: SM04690
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study

Experimental: 0.23 mg SM04690
Single intra-articular injection of 0.23 mg SM04690 in 2 mL vehicle
Drug: SM04690
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study

Placebo Comparator: Vehicle
Single intra-articular injection of 0 mg SM04690 in 2 mL vehicle
Drug: placebo
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study

Sham Comparator: Sham
Single intra-articular injection of 0 mg SM04690 in 0 mL vehicle
Drug: placebo
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study




Primary Outcome Measures :
  1. Change from baseline OA pain in the target knee (NRS) [ Time Frame: Baseline and Week 24 ]
    Evaluate change from baseline OA pain in the target knee as assessed by the weekly averages of subject-reported daily pain Numeric Rating Scale (NRS).

  2. Change from baseline OA pain in the target knee (WOMAC) [ Time Frame: Baseline and Week 24 ]
    Evaluate change from baseline OA pain in the target knee as assessed by subject-reported Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscore. 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, stiffness, and physical functioning of the joints.

  3. Change from baseline OA function in the target knee (WOMAC) [ Time Frame: Baseline and Week 24 ]
    Evaluate change from baseline OA function in the target knee as assessed by WOMAC physical function subscore.

  4. Change from baseline in medial JSW of the target knee [ Time Frame: Baseline and Week 24 ]
    Evaluate change from baseline in medial joint space width (JSW) as documented by radiograph of the target knee.


Secondary Outcome Measures :
  1. Occurence of treatment-emergent adverse events (TEAEs) [ Time Frame: Baseline and Week 24 ]
    Evaluate the safety of SM04690 as measured by TEAEs

  2. Change from baseline OA disease activity (subject-reported) [ Time Frame: Baseline and Week 24 ]
    Evaluate change from baseline OA disease activity as assessed by Patient Global Assessment.


Other Outcome Measures:
  1. Change from baseline OA pain in the target knee (WOMAC) [ Time Frame: Baseline, Weeks 4, 8, 12, 16 and 20 ]
    Evaluate change from baseline OA pain in the target knee as assessed by subject-reported WOMAC pain subscore.

  2. Change from baseline OA function in the target knee (WOMAC) [ Time Frame: Baseline, Weeks 4, 8, 12, 16 and 20 ]
    Evaluate change from baseline OA function in the target knee as assessed by subject-reported WOMAC physical function subscore.

  3. Change from baseline OA symptoms in the target knee (WOMAC) [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24 ]
    Evaluate change from baseline OA symptoms in the target knee as assessed by subject-reported WOMAC total score.

  4. Change from baseline OA pain in the target knee (NRS) [ Time Frame: Baseline, and Weeks 1 through 23 ]
    Evaluate change from baseline OA pain in the target knee as assessed by the weekly averages of subject-reported daily pain NRS.

  5. Change from baseline OA disease activity (subject-reported) [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24 ]
    Evaluate change from baseline OA disease activity as assessed by Patient Global Assessment.

  6. Change from baseline OA function in the target knee (KOOS) [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24 ]
    Evaluate change from baseline OA function in the target knee as assessed by Knee Injury and Osteoarthritis Outcome Score (KOOS). KOOS is a widely-used, non-proprietary tool used by health professionals to assess a subject's opinion about their knee and associated problems. KOOS evaluates pain, symptoms, 2 types of physical function, and knee-related quality of life.

  7. Change from baseline OA function in the target knee (KOOS-PS) [ Time Frame: Baseline, and Weeks 1 through 24 ]
    Evaluate change from baseline OA function in the target knee at each week as assessed by KOOS Physical Function Short Form (KOOS-PS). KOOS-PS is derived from the KOOS and is used to assess a subject's opinion about the difficulties they experience with activity due to problems with their knee.

  8. Change from baseline OA disease activity (physician-reported) [ Time Frame: Baseline, Weeks 4, 12 and 24 ]
    Evaluate change from baseline OA disease activity as assessed by Physician Global Assessment.

  9. Change over time in NSAID usage for the treatment of OA pain [ Time Frame: Baseline, and Weeks 1 through 24 ]
    Evaluate change over time in non-steroidal anti-inflammatory drug (NSAID) usage for the treatment of OA pain as assessed by weekly averages of daily pain medication electronic diary responses.

  10. Outcome differences between treatment with sham or placebo injections [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24 ]
    Evaluate outcome differences between treatment with sham or placebo injections



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.


Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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
  • 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

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): NCT03122860


  Show 74 Study Locations
Sponsors and Collaborators
Samumed LLC
Investigators
Study Director: Yusuf Yazici, M.D. Samumed LLC

Responsible Party: Samumed LLC
ClinicalTrials.gov Identifier: NCT03122860     History of Changes
Other Study ID Numbers: SM04690-OA-04
First Posted: April 21, 2017    Key Record Dates
Last Update Posted: August 15, 2018
Last Verified: August 2018
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

Additional relevant MeSH terms:
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases