Study of Resiniferatoxin for Knee Pain in Moderate to Severe Osteoarthritis

Study Overview
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Brief Summary
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This study evaluates the safety of resiniferatoxin in patients with moderate to severe knee pain due to osteoarthritis.

Detailed Description
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This study is to evaluate the safety of resiniferatoxin administered intra-articularly to subjects with moderate to severe knee pain due to osteoarthritis (OA). It is also to assess the preliminary efficacy of resiniferatoxin to relieve knee pain when walking.

Official Title
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Phase 1b Double-blind Study to Assess the Safety, Tolerability and Preliminary Efficacy of Intra-articular Administration of Resiniferatoxin Versus Placebo for the Treatment of Pain Due to Moderate to Severe Osteoarthritis of the Knee

Conditions
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Osteoarthritis, Knee, Pain, Knee

Intervention / Treatment
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* Drug: Resiniferatoxin
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age: 35 years to 85 years Diagnosis of moderate to severe pain due to OA: Moderate to severe osteoarthritis, based on American College of Rheumatology (ACR) criteria BMI < 45 kg/m2 Pain in the target knee has been treated with at least 2 analgesic agents, including at least one NSAID Prior failure in at least two prior analgesic agents (at least one NSAID) Willing to abstain from other intra-articular treatments of the knee or any knee surgery for at least 24 weeks after treatment Ability to comply with the study and give informed consent If on an opioid medication, stable dose for at least 4 weeks prior to injection with no increase in dose leading up to study injection If on NSAIDs, be on a stable analgesic regimen for at least 4 weeks prior to injection If on pain regimens other than opioid medication or NSAIDs, be on a stable regimen for at least 30 days Is in good general health and is considered to have a physical status that is American Society of Anesthesiologists (ASA) category ≤ 3 Able to comply with study procedures, including the recording of daily questionnaires Exclusion Criteria: Has evidence or history of a coagulopathy or hemostasis problem at Screening or Baseline (Day 1) Treatment knee injections with corticosteroids within 30 days or hyaluronic acid within 3 months prior to the procedure If on opioid analgesics, an upper limit of 30 mg/day of oral morphine sulfate, 20 mg/day of oxycodone, 30 mg/day of hydrocodone, or 300 mg/day of tramadol, or equivalent Any of the following lab abnormalities within one week of the treatment day: Platelet count <100,000 cells/mm3 Total neutrophil count <1500 cells/mm3 Serum creatinine ≥ 1.5 x ULN Alanine aminotransferase (ALT) > 3.0 x ULN Aspartate aminotransferase (AST) > 3.0 x ULN Alkaline phosphatase > 2.0 ULN Bilirubin > 1.5 x ULN INR > 1.5 x ULN Temperature ≥ 100.4°F or other evidence of an infection Concurrent use of opioids for indications other than knee pain History of substance abuse Has an allergy or hypersensitivity to chili peppers, capsaicin, resiniferatoxin or radiographic contrast agents Female subjects who are pregnant at Screening or are planning on becoming pregnant, or are currently breastfeeding Subjects with any medical condition or comorbidities that could adversely impact study participation or safety, conduct of the study, or interfere with pain assessments Subjects who have participated in a clinical study of an investigational drug within 4 half-lives of Screening or are scheduled to receive and investigational agent while participating in this study Sensory peripheral neuropathy that is CTCAE Grade 2 or higher at Screening Arterial or venous thrombi, myocardial infarction, admission for unstable angina, cardiac angioplasty, or stenting within 12 months prior to Screening Evidence or history of any hemorrhage or bleeding event that is higher than CTCAE Grade 1 within 4 weeks prior to injection. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or C. Positive tests for HIV-1 or -2 antibodies, hepatitis B surface antigen, or hepatitis C antibodies. Concurrent medical or arthritic conditions that could interfere with evaluation of the index knee joint including fibromyalgia, rheumatoid arthritis, or other inflammatory arthropathies affecting the knee joint Subjects with significant pain in other joints may be excluded at the discretion of the investigator Subject has undergone arthroscopic or open surgery to the knee within 6 months of the planned injection day Subject has undergone replacement surgery of the treatment knee Presence of surgical hardware or other foreign bodies in the treatment knee

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Resiniferatoxin<br>Resiniferatoxin is administered as a one-time dose, intra-articularly at a dose level of 5ug, 12.5ug, 20ug, 25ug, or 30ug. | Drug: Resiniferatoxin<br>* Resiniferatoxin is a compound purified from natural sources.<br>* Other names: RTX;|
| Placebo Comparator: Saline<br>Saline is administered as a one-time dose, intra-articularly. | Drug: Saline<br>* Saline is a normal physiological solution<br>* Other names: Normal saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety measurement | Incidence and severity of adverse events | baseline through week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of knee pain when walking | Improvement in pain score versus baseline using the WOMAC Osteoarthritis Index question A1 (pain on walking, 11-point numerical rating scale) | baseline through week 52 |