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

Biosplice Therapeutics

Status and phase

Terminated

Phase 2

Conditions

Knee Osteoarthritis

Treatments

Drug: SM04690

Study type

Interventional

Funder types

Industry

Identifiers

NCT03706521

SM04690-OA-08

Details and patient eligibility

About

This phase 2 study is a single center, open-label study of SM04690 injected intraarticularly (IA) into the target knee (most painful) joint of moderately to severely symptomatic osteoarthritis (OA) subjects at a single dose of 0.07 mg SM04690 per 2 mL injection. This study will utilize magnetic resonance imaging (MRI) (including T1rho and T2 mapping pulse sequence MRI, three-dimensional spoiled gradient recalled [3D-SPGR] pulse sequence MRI, and whole organ MRI scoring [WORMS]), radiographic imaging, Western Ontario and McMaster Universities Arthritis Index (WOMAC) and patient reported outcomes (PROs) for data collection to assess efficacy outcome measures.

Enrollment

13 patients

Sex

All

Ages

40 to 80 years old

Volunteers

No Healthy Volunteers

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