Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
Inclusion Criteria:
1. Male or female patients 35 years of age or older, with a Body Mass Index (BMI) of 18.0
to 40.0 kg/m2 and a total body weight of ≥50.0 kg for males and ≥45.5 kg for females.
2. Patients with chronic knee pain resulting from osteoarthritis for greater than 6
months prior to study Screening Visit 1 that interferes with functional activities
(e.g., ambulation, prolonged standing, etc.).
3. Patients currently experiencing continued pain despite receiving at least 3 months of
conservative treatments, inclusive of activity modification, home exercise, protective
weight bearing, and/or use of analgesics (e.g., acetaminophen or NSAIDs).
4. Patients with a baseline average pain score of ≥ 6 on an 11-point NRS scale as "usual
level of pain over the past 24 hours during weight-bearing activities" for the index
knee at Screening. The baseline average pain score is computed by finding the mean of
the daily NRS pain intensity scores reported during the 7-day run in period.
5. Patients with Kellgren-Lawrence Grade 2 (mild) or Grade 3 (moderate) radiologically
confirmed osteoarthritis (via x-ray/MRI/CT) within 6 months of study Screening Visit
1.
6. Patients with a baseline Knee Injury and Osteoarthritis Outcome Score (KOOS) pain
subscale score ≥ 19 and ≤ 67 in the index knee.
7. Patients taking analgesics, inclusive of membrane stabilizers (e.g.,
Neurontin/gabapentin) and/or antidepressants (e.g., Cymbalta/duloxetine), for
osteoarthritis associated knee pain must be on a stable dose for at least 6 weeks
prior to study Screening Visit 1. Patients must agree to not alter the dose of
analgesics for the duration of the study without prior approval from the Investigator.
8. Female patients of childbearing potential who are sexually active with a male partner
must be willing to use one of the following acceptable contraceptive methods
throughout the study and for 30 days after the last study drug administration:
1. Intra-uterine contraceptive device placed at least 4 weeks prior to study drug
administration;
2. Male condom with intravaginally applied spermicide starting at least 21 days
prior to study drug administration;
3. Hormonal contraceptives starting at least 4 weeks prior to study drug
administration must agree to use the same hormonal contraceptive throughout the
study;
4. Sterile male partner (vasectomized since at least 6 months).
9. Female patients of non-childbearing potential as defined below:
1. Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable
cases a blood sample with simultaneous follicle stimulating hormone (FSH) and
estradiol levels consistent with menopause).
2. Pre-menopausal females with one of the following:
- Documented tubal ligation
- Documented hysteroscopic tubal occlusion procedure with follow-up
confirmation of bilateral tubal occlusion
- Hysterectomy
- Documented bilateral oophorectomy.
10. Patients must agree to see one treating physician (study Investigator) for knee pain
treatment for study duration.
11. Patients who have a positive response to a single genicular nerve block of the index
knee using 1.5 - 3mL of lidocaine 2% solution administration to the genicular nerves
planned for treatment in each cohort (0.5mL per nerve). A positive response to the
qualifying lidocaine prognostic block is defined as ≥ 80% pain reduction within 60
minutes of receiving the lidocaine injections and ≥ 80% pain relief for a duration of
at least 60 minutes as documented on a standardized 6-hour pain log.
12. Patients must be able to understand and be able to complete all assessments associated
with the study outcome measures.
13. Patients must be able to understand the informed consent and be willing to provide
written informed consent. Patients must be able to comply with the requirements of the
protocol for the entire duration of the study.
Exclusion Criteria:
1. Patients with evidence of inflammatory arthritis (e.g., rheumatoid arthritis) or any
other systemic inflammatory condition (e.g., gout, pseudogout). 2. Current diagnosis of
fibromyalgia. 3. Patients with evidence of neuropathic pain affecting the index knee. 4.
Patients with prior or planned lower limb amputation. 5. Patients who have received an
intra-articular steroid injection into the index knee within 90 days of study Screening
Visit 1. 6. Patients who have received hyaluronic acid injection, Platelet Rich Plasma
(PRP), stem cell or arthroscopic debridement/lavage injection into the index knee within
180 days of study Screening Visit
- Patients who have received prior radiofrequency ablation or any other neurolytic
procedure of the genicular nerves of the index knee within 1 year of study Screening
Visit 1.
- Patients who have received prior partial, resurfacing, or total knee arthroplasty of
the index knee (residual hardware).
- Patients with clinically significant ligamentous laxity of the index knee as per
Investigator discretion.
- Patients with clinically significant valgus/varus deformities or evidence of pathology
(other than osteoarthritis of the knee) that materially affects gait or function of
the index knee or is the underlying cause of the knee pain and/or functional
limitations.
- Patients who are extremely thin and those with minimal subcutaneous tissue thickness
that could place the patient at risk of a chemical skin burn, at the discretion of the
Investigator.
- Patients with a pending or active compensation claim, litigation or disability
remuneration (possibility of secondary gain).
- Patients with chronic pain associated with significant psychosocial dysfunction.
- Patients with a Patient Health Questionnaire - 9 (PHQ-9) score of >10 (indicative of a
state of moderate depression).
- Patients with a systemic infection, active joint infection, or localized infection at
the planned needle entry sites (patient may be considered for inclusion once infection
is resolved).
- Patients with history of uncontrolled coagulopathy or unexplained or uncontrollable
bleeding that cannot be corrected, and patients with coagulopathy or who are being
treated with anticoagulants.
- Patients with moderate to severe hepatic impairment or moderate to severe renal
impairment.
- Identifiable anatomical variability that would materially alter the procedure as
described in the protocol.
- Patients currently prescribed opioid medications at a dose of >50 daily morphine
equivalents.
- Patients with uncontrolled immunosuppression (e.g., AIDs, cancer, diabetes) as per
Investigator discretion.
- Female patients who are pregnant or planning to become pregnant during the duration of
the study.
- Female patients who are breast-feeding.
- Patients who are unable or unwilling to comply with the requirements of the protocol.
- Patients taking any of the following concurrent medications/over-the counter products
(refer to Appendix 8 in full protocol for a list of applicable medications): c.
Probenecid or other organic anion transporter (OAT3) inhibitors. d. Inhibitors of
CYP2E1, such as disulfiram.
- Patients with known allergies or hypersensitivity to iodinated contrast medium and
gadolinium-based contrast medium. Known allergies or hypersensitivity to phenol and/or
lidocaine and/or their excipients.
- Patients with a documented history or evidence of alcohol or drug abuse within 1 year
of study screening visit 1.
- Participation in a clinical research study involving the administration of an
investigational or marketed drug or device within 30 days of study Screening Visit 1,
administration of a biological product in the context of a clinical research study
within 90 days prior to the first dosing, or concomitant participation in an
investigational study involving no drug or device administration.
- Patients with clinically significant ECG abnormalities or vital sign abnormalities at
during study Screening Visit 1. Patients with ECG or vital sign abnormalities deemed
nonclinically significant or unlikely to result in clinical compromise by the
Principal Investigator may be considered for study inclusion.
- Patients with clinically significant laboratory results (as judged by the Principal
Investigator).
- Any condition, in the opinion of the Principal Investigator, that may pose a
significant risk to the patient, confound the results of the study or interfere
significantly with the patient's participation in the study.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 2/28/23. Questions regarding updates should be directed to the study team contact.