Study to Evaluate Resiniferatoxin in Patients With Knee Osteoarthritis Whose Total Knee Replacement Surgery is Delayed

A Phase 3, Randomized, Multi-center, Blinded, Placebo-controlled Study to Evaluate the Efficacy and Safety of Intra-articular Resiniferatoxin Versus Placebo to Manage Pain in Patients With Osteoarthritis of the Knee Whose Total Knee Replacement Surgery is Delayed

Efficacy and safety study of resiniferatoxin versus placebo to manage pain in patients with knee osteoarthritis whose TKR surgery is delayed

Study Overview

• Status: Withdrawn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

Detailed Description

This study evaluates the efficacy and safety of intra-articular resiniferatoxin (RTX) versus placebo to manage pain in patients with osteoarthritis of the knee whose Total Knee Replacement surgery is delayed.

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Able to give informed consent and comply with the study
• Diagnosis of osteoarthritis (OA) in the index knee
• Combined WOMAC A (pain) and C (function) subscale score of ≥ 23 at screening, using the WOMAC 5-point Likert scale
• Eligible for total knee replacement (TKR) surgery but unable to schedule surgery or undergo scheduled surgery
• In good general health; American Society of Anesthesiologists (ASA) physical status category ≤3
• Willing to use contraception for at least 30 days after receiving the study drug
• Able to understand and complete study-related forms and adequately communicate with the Investigator and site staff

Exclusion Criteria:

• Pre-existing osteonecrosis, subchondral insufficiency fracture, or knee pain attributable to disease other than OA which may confound the ability to assess response to treatment
• Concurrent medical or arthritic conditions that could interfere with evaluation of the index knee joint including, metabolic diseases, gout/pseudogout, hemochromatosis, acromegaly, fibromyalgia, rheumatoid arthritis, or other inflammatory arthropathies affecting the knee joint
• Participants with significant pain in the back or other joints (ex. hip pain) which may confound discrimination of pain assessment in index knee, as judged by the Investigator
• Undergone arthroscopic surgery of the index knee within 6 months of study drug administration, or open surgery to the index knee within 24 months of study drug administration
• Undergone replacement surgery of the index knee
• Presence of surgical hardware or other foreign bodies in the index knee
• Index knee injections with corticosteroids within 30 days, or hyaluronic acid within 3 months, or platelet-rich plasma within 6 months prior to study drug administration.
• Concurrent use of opioids for indications other than knee pain
• Arterial or venous thrombi (including stroke), myocardial infarction, hospital admission for unstable angina, cardiac angioplasty, or stenting within 12 months prior to Screening.
• Sensory peripheral neuropathy in the distal aspect of the target limb that is of moderate severity or higher at Screening
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or hepatitis C; positive tests for HIV-1 or -2 antibodies, hepatitis B surface antigen, or hepatitis C antibodies
• Specified laboratory abnormalities within 1 week of study drug administration
• History within the past 2 years of substance abuse, including alcohol
• Allergy or hypersensitivity to chili peppers, capsaicin, resiniferatoxin, acetaminophen, tramadol, radiographic contrast agents, or any of the agents to be used for sedation, anesthesia or nerve block on the day of study drug administration
• Female participants who are pregnant, planning on becoming pregnant within 30 days of receiving study drug, or are breastfeeding at Screening
• Any medical condition or medical comorbidities that, in the Investigator's opinion, could adversely impact study participation or safety, conduct of the study, or interfere with pain assessments
• Participated in a clinical study of an investigational drug within 4 half-lives of Screening or are scheduled to receive an investigational agent (therapy or device) while participating in this study

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 administered once intra-articularly	Drug: Resiniferatoxin; Resiniferatoxin is a compound purified from natural sources.; Other Names: RTX
Placebo Comparator: Placebo; 5 mL of diluent in normal saline administered once intra-articularly	Drug: Placebo; Diluent in normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in WOMAC pain and function subscales combined score	Change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) 3.1 numerical rating scale (NRS) [0-10 scale] Pain and Function combined score. The combined score ranges from 0 to 220; a higher score indicates greater severity of disease.	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of RTX: Incidence and severity of adverse events	Incidence and severity of adverse events	Baseline through Week 12
Change in analgesic usage	Change in analgesic medication usage as reported by subjects	Baseline to Week 4, Week 8, Week 12
Change in WOMAC pain and function subscales combined score	Change in the WOMAC 3.1 NRS [0-10 scale] Pain and Function combined score. The combined score ranges from 0 to 220; a higher score indicates greater severity of disease.	Baseline to Week 4, Week 8
Patient Global Impression of Change (PGIC) in index knee pain	Rating of change in index knee pain using the 7-point PGIC scale where 1 = very much improved and 7 = very much worsened.	Baseline to Week 4, Week 8, Week 12

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): April 1, 2021
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: May 8, 2020
• First Submitted That Met QC Criteria: May 12, 2020
• First Posted (Actual): May 13, 2020

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

• Keywords: osteoarthritis; knee pain
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: STI-RTX-3004

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