A Phase 3 Study to Evaluate the Efficacy and Safety of Resiniferatoxin for Pain Due to Osteoarthritis of the Knee

A Phase 3 Placebo-controlled Study to Evaluate the Efficacy and Safety of Intra-articular Administration of Resiniferatoxin Versus Placebo for the Treatment of Moderate to Severe Pain Due to Osteoarthritis of the Knee

This study evaluates the efficacy and safety of intra-articular injection of resiniferatoxin in patients with moderate to severe knee pain due to osteoarthritis.

Study Overview

• Status: Withdrawn
• Conditions: Osteoarthritis, Knee; Knee Pain Chronic
• Intervention / Treatment: Drug: Placebo; Drug: Resiniferatoxin

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).

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Resiniferatoxin; 12.5 ug of Resiniferatoxin in 5 mL volume is administered as a one-time dose, intra-articularly	Drug: Resiniferatoxin; Receiving Resiniferatoxin injection; Other Names: RTX
Placebo Comparator: Placebo; Placebo formulation in 5 mL volume administered intra-articularly	Drug: Placebo; Receiving Placebo injection; Other Names: Diluent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in index knee pain with walking	Change in the weekly mean of Average Daily Pain (ADP) scores in the index knee, using the 10-point Numerical Pain Rating Scale (NPRS)	Baseline through Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) change in average pain in the index knee	AUC calculated on change in the average pain in the index knee over the previous 24 hours, using the NPRS (0-10)	Baseline through Week 12
Change in index knee pain with walking	Change in the weekly mean of ADP scores in the index knee, using the NPRS (0-10)	Baseline through Week 26
AUC change in average pain in the index knee	AUC calculated on change in the average pain in the index knee over the previous 24 hours, using the NPRS (0-10)	Baseline through Week 26
Duration of effect of a single injection in the index knee	Time to return to baseline pain score, based on weekly average NPRS (0-10) scores	Baseline through return to Baseline
Change in index knee pain, stiffness, and physical function	Change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score	Baseline through Week 12, Week 26, and Week 52
Change in the average pain in the index knee	Change in the WOMAC A pain subscale	Baseline through Week 12, Week 26, and Week 52
Change in the average stiffness in the index knee	Change in the WOMAC B function subscale	Baseline through Week 12, Week 26, and Week 52
Change in the average function in the index knee	Change in the WOMAC C stiffness subscale	Baseline through Week 12, Week 26, and Week 52
Change in index knee pain with walking	Change in the weekly mean of ADP scores in the index knee, using the NPRS (0-10)	Baseline through Week 52
AUC change in average pain in the index knee	AUC calculated on change in the average pain in the index knee over the previous 24 hours, using the NPRS (0-10)	Baseline through Week 52
Change in quality of life (QOL) - SF-36 Health Survey	Change in QOL as measured by the SF-36 Health Survey	Baseline through Week 12, Week 26, and Week 52
Change in quality of sleep	Change in quality of sleep as measured by the MOS Sleep Scale	Baseline through Week 12, Week 26, and Week 52
Patient Global Impression of Change	Rating of change in index knee pain using the PGIC scale	At Week 12, Week 26, and Week 52
Change in QOL - EQ-5D-5L	Change in QOL as measured by the EQ-5D-5L	Baseline through Week 12, Week 26, and Week 52

Collaborators and Investigators

• Sponsor: Sorrento Therapeutics, Inc.
• Investigators: Study Director: Monica Luchi, MD, Sorrento Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2020
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: August 2, 2019
• First Submitted That Met QC Criteria: August 2, 2019
• First Posted (Actual): August 5, 2019

Study Record Updates

• Last Update Posted (Actual): November 9, 2021
• Last Update Submitted That Met QC Criteria: November 2, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: STI-RTX-3001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No