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

• ClinicalTrials.gov Identifier: NCT04386980
• Recruitment Status: Not yet recruiting
• First Posted: May 13, 2020
• Last Update Posted: June 25, 2020
• Sponsor: Sorrento Therapeutics, Inc.
• Information provided by (Responsible Party): Sorrento Therapeutics, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Osteoarthritis, Knee; Osteo Arthritis Knee; Knee Pain Chronic	Drug: Resiniferatoxin; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: August 2020
• Estimated Primary Completion Date: June 2021
• Estimated Study Completion Date: June 2021

Arms and Interventions

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 Name: RTX
Placebo Comparator: Placebo; 5 mL of diluent in normal saline administered once intra-articularly	Drug: Placebo; Diluent in normal saline

Outcome Measures

Primary Outcome Measures :

1. Change in WOMAC pain and function subscales combined score [ Time Frame: Baseline to Week 12 ]
   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.

Secondary Outcome Measures :

1. Safety of RTX: Incidence and severity of adverse events [ Time Frame: Baseline through Week 12 ]
   Incidence and severity of adverse events
2. Change in analgesic usage [ Time Frame: Baseline to Week 4, Week 8, Week 12 ]
   Change in analgesic medication usage as reported by subjects
3. Change in WOMAC pain and function subscales combined score [ Time Frame: Baseline to Week 4, Week 8 ]
   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.
4. Patient Global Impression of Change (PGIC) in index knee pain [ Time Frame: Baseline to Week 4, Week 8, Week 12 ]
   Rating of change in index knee pain using the 7-point PGIC scale where 1 = very much improved and 7 = very much worsened.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Sponsors and Collaborators

Sorrento Therapeutics, Inc.

Investigators

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

More Information

• Responsible Party: Sorrento Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT04386980
• Other Study ID Numbers: STI-RTX-3004
• First Posted: May 13, 2020
• Last Update Posted: June 25, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sorrento Therapeutics, Inc.:

osteoarthritis; knee pain

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases