Knee Pain Chronic, Osteoarthritis, Knee
Conditions
Brief summary
This study evaluates the efficacy and safety of intra-articular injection of resiniferatoxin in patients with moderate to severe knee pain due to osteoarthritis.
Detailed description
This study is to evaluate the analgesic efficacy and safety of resiniferatoxin administered intra-articularly to subjects with moderate to severe knee pain due to osteoarthritis (OA).
Interventions
DRUGPlacebo
Receiving Placebo injection
DRUGResiniferatoxin
Receiving Resiniferatoxin injection
Sponsors
Sorrento Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
The treatment assigned to each subject is blinded to the subject, investigators, and sponsor study team.
Eligibility
Sex/Gender
ALL
Age
35 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Male or female 35 to 85 years of age (inclusive). * Diagnosis of moderate to severe pain in the index knee due to OA. * Pain in the non-index knee is less than pain in the index knee. * Body mass index ≤40 kg/m². * Experienced treatment failure with at least 2 prior categories of therapies. * Able to understand and complete study-related forms and communicate with the Investigator and/or site staff. Key
Exclusion criteria
* Evidence or history of a serious coagulopathy or hemostasis problem, such as inherited bleeding disorders or thrombocytopenia. * History of or current condition of poorly controlled hypertension, QTc prolongation, history of risk factors for Torsades de Pointes, or family history of long QT syndrome; or is using concomitant medications that prolong the QT interval. * Received index knee injections with corticosteroids within 30 days, or hyaluronic acid within 3 months, or platelet-rich plasma within 6 months prior to the injection day. * Pre-existing osteonecrosis, subchondral insufficiency fracture, severe bone on bone OA, or knee pain attributable to disease other than OA. * Instability or misalignment in the index knee. * Concurrent use of opioids or indications other than knee pain. * History within the past 2 years of substance abuse, including alcohol. * Allergy or hypersensitivity to chili peppers, capsaicin, resiniferatoxin, acetaminophen, tramadol, or radiographic contrast agents. * Female participants who are pregnant, planning on becoming pregnant, or currently breastfeeding. * Any medical condition or comorbidities that, in the Investigator's opinion, could adversely impact study participation or safety, conduct of the study, or interfere with pain assessments. * Sensory peripheral neuropathy that is of moderate severity or higher. * Arterial or venous thrombi (including stroke), myocardial infarction, hospital admission for unstable angina, cardiac angioplasty, or stenting within the past 12 months. * Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or hepatitis C. Participants with these viral infections who are receiving or have received antiviral treatment and have a viral load that is undetectable are eligible. * Concurrent medical or arthritic conditions that could interfere with the evaluation of the index knee joint including chondromalacia patellae, metabolic diseases, gout/pseudogout, hemochromatosis, acromegaly, fibromyalgia, rheumatoid arthritis, or other inflammatory arthropathies affecting the knee joint. * Undergone arthroscopic surgery of the index knee within 6 months of the injection day, or open surgery to the index knee within 24 months of the injection day. * Undergone replacement surgery of the index knee. * Presence of surgical hardware or other foreign bodies in the index knee.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in index knee pain with walking | Baseline through Week 12 | Change in the weekly mean of Average Daily Pain (ADP) scores in the index knee, using the 10-point Numerical Pain Rating Scale (NPRS) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in index knee pain with walking | Baseline through Week 26 | Change in the weekly mean of ADP scores in the index knee, using the NPRS (0-10) |
| AUC change in average pain in the index knee | Baseline through Week 26 | AUC calculated on change in the average pain in the index knee over the previous 24 hours, using the NPRS (0-10) |
| Duration of effect of a single injection in the index knee | Baseline through return to Baseline | Time to return to baseline pain score, based on weekly average NPRS (0-10) scores |
| Change in index knee pain, stiffness, and physical function | Baseline through Week 12, Week 26, and Week 52 | Change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score |
| Change in the average pain in the index knee | Baseline through Week 12, Week 26, and Week 52 | Change in the WOMAC A pain subscale |
| Area under the curve (AUC) change in average pain in the index knee | Baseline through Week 12 | AUC calculated on change in the average pain in the index knee over the previous 24 hours, using the NPRS (0-10) |
| Change in the average function in the index knee | Baseline through Week 12, Week 26, and Week 52 | Change in the WOMAC C stiffness subscale |
| Change in quality of life (QOL) - SF-36 Health Survey | Baseline through Week 12, Week 26, and Week 52 | Change in QOL as measured by the SF-36 Health Survey |
| Change in quality of sleep | Baseline through Week 12, Week 26, and Week 52 | Change in quality of sleep as measured by the MOS Sleep Scale |
| Patient Global Impression of Change | At Week 12, Week 26, and Week 52 | Rating of change in index knee pain using the PGIC scale |
| Change in QOL - EQ-5D-5L | Baseline through Week 12, Week 26, and Week 52 | Change in QOL as measured by the EQ-5D-5L |
| Change in the average stiffness in the index knee | Baseline through Week 12, Week 26, and Week 52 | Change in the WOMAC B function subscale |
Outcome results
None listed