| Eligibility |
Inclusion Criteria:
- Ambulatory (single assistive devices such as canes allowed if needed less than 50% of
the time, subjects requiring a walker are excluded)
- 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)
- Pain compatible with OA of the knee(s) for at least 26 weeks prior to the Screening
Visit
- Primary source of pain throughout the body is due to OA in the target knee
- Daily OA knee pain diary average Numeric Rating Scale (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
- Baseline mJSW by radiograph between 2 and 4 mm, inclusive, in the target knee at the
Screening Visit as assessed by independent central readers
- Total WOMAC score of 96-192 (out of 240) for the target knee at Day 1 regardless of if
the subject is on symptomatic oral treatment
- Negative drug test for amphetamine, methamphetamine, 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 the Screening Visit
- Subjects with depression or anxiety must be clinically stable for 12 weeks prior to
the Screening Visit 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
- Subject's Screening Visit must occur while enrollment into the study is open
Exclusion Criteria:
- Women who are pregnant, lactating, or have a positive pregnancy test result at the
Screening Visit
- Women of childbearing potential who are sexually active, and who are not willing to
use an acceptable method of birth control during the study period
- Men of childbearing potential who are sexually active and have a partner who is
capable of becoming pregnant, neither of whom are agreeable to using an acceptable
method of birth control during the study period
- Body mass index (BMI) > 40
- Partial or complete joint replacement in either knee
- Currently requires: a) regular use (in the opinion of the Investigator) of ambulatory
assistive devices (e.g., wheelchair, parallel bars, walker, canes, or crutches), or b)
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 the Screening Visit
according to the Kellgren-Lawrence (KL) grading of knee OA as assessed by independent
central readers
- Previous treatment with SM04690
- Subjects who have previously failed screening on this protocol and fail to meet
re-screening criteria
- Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to the Screening
Visit
- 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
- 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 the Screening Visit
- Clinically significant abnormal screening hematology values, blood chemistry values,
or urinalysis values as determined by the Investigator
- Any condition, including laboratory findings not included in the Screening Visit
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
- 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
- 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
- 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 to the Screening
Visit, or planned participation in any such trial; the last date of participation in
the trial, not the last date of receipt of investigational product, must be at least 8
weeks prior to the Screening Visit
- 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 the Screening Visit; treatment
of the target knee with intra-articular glucocorticoids greater than 12 weeks prior to
the Screening Visit is allowed
- Treatment with systemic glucocorticoids greater than 10 mg prednisone or the
equivalent per day within 4 weeks prior to the Screening Visit
- Effusion of the target knee clinically requiring aspiration within 12 weeks prior to
the Screening Visit
- Use of electrotherapy, acupuncture, and/or chiropractic treatments for knee OA within
4 weeks prior to the Screening Visit
- 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
- Current use, or use within 12 weeks prior to the Screening Visit, of centrally acting
analgesics
- Current use, or use within 12 weeks prior to the Screening Visit, of anticonvulsants
(refer to Appendix 2)
- Subjects requiring the usage of opioids >1x per week within 12 weeks prior to the
Screening Visit
- Topical local anesthetic agents (gels, creams, or patches such as the Lidoderm patch)
used for the treatment of knee OA within 7 days of the Screening Visit
- 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
the Screening Visit will be excluded.
- If on nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of OA pain,
subjects who have not maintained a stable regimen in the opinion of the Investigator
at the Screening Visit
- Any contraindications for performing MRI
- Subjects who have a current or pending disability claim, workers' compensation, or
litigation(s) that may compromise response to treatment
- 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
- 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
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