Study of Resiniferatoxin for Knee Pain in Moderate to Severe Osteoarthritis

• Sponsor: Sorrento Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03542838
• Collaborator: (none)
• Enrollment: 94
• Locations: 4
• Arms: 2
• Actual Duration (Months): 31
• Patients Per Site: 23.5
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis, Knee; Pain, Knee	Drug: Resiniferatoxin; Drug: Saline	Phase 1

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 94 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Except for the sentinel subject, the treatment assigned to each subject in the dose-escalation cohorts is blinded to the subject, investigators, and sponsor study team. The sentinel subject, the first subject in each dose-escalation cohort, is dosed with resiniferatoxin in an open-label fashion. Subjects in the dose-escalation cohorts who received placebo may receive resiniferatoxin in an open-label fashion after unblinding. All subjects in the dose-expansion cohorts are dosed with resiniferatoxin in an open-label fashion.
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jul 12, 2018
• Actual Primary Completion Date: Apr 13, 2020
• Actual Study Completion Date: Feb 11, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Safety measurement [baseline through week 52]

   Incidence and severity of adverse events

Secondary Outcome Measures

1. Improvement of knee pain when walking [baseline through week 52]

   Improvement in pain score versus baseline using the WOMAC Osteoarthritis Index question A1 (pain on walking, 11-point numerical rating scale)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

1. Age: 35 years to 85 years

2. Diagnosis of moderate to severe pain due to OA: Moderate to severe osteoarthritis, based on American College of Rheumatology (ACR) criteria

3. BMI < 45 kg/m2

4. Pain in the target knee has been treated with at least 2 analgesic agents, including at least one NSAID

5. Prior failure in at least two prior analgesic agents (at least one NSAID)

6. Willing to abstain from other intra-articular treatments of the knee or any knee surgery for at least 24 weeks after treatment

7. Ability to comply with the study and give informed consent

8. 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

9. If on NSAIDs, be on a stable analgesic regimen for at least 4 weeks prior to injection

10. If on pain regimens other than opioid medication or NSAIDs, be on a stable regimen for at least 30 days

11. Is in good general health and is considered to have a physical status that is American Society of Anesthesiologists (ASA) category ≤ 3

12. Able to comply with study procedures, including the recording of daily questionnaires

Exclusion Criteria:

1. Has evidence or history of a coagulopathy or hemostasis problem at Screening or Baseline (Day 1)

2. Treatment knee injections with corticosteroids within 30 days or hyaluronic acid within 3 months prior to the procedure

3. 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

4. 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

1. Concurrent use of opioids for indications other than knee pain

2. History of substance abuse

3. Has an allergy or hypersensitivity to chili peppers, capsaicin, resiniferatoxin or radiographic contrast agents

4. Female subjects who are pregnant at Screening or are planning on becoming pregnant, or are currently breastfeeding

5. Subjects with any medical condition or comorbidities that could adversely impact study participation or safety, conduct of the study, or interfere with pain assessments

6. 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

7. Sensory peripheral neuropathy that is CTCAE Grade 2 or higher at Screening

8. Arterial or venous thrombi, myocardial infarction, admission for unstable angina, cardiac angioplasty, or stenting within 12 months prior to Screening

9. Evidence or history of any hemorrhage or bleeding event that is higher than CTCAE Grade 1 within 4 weeks prior to injection.

10. 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.

11. 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

12. Subjects with significant pain in other joints may be excluded at the discretion of the investigator

13. Subject has undergone arthroscopic or open surgery to the knee within 6 months of the planned injection day

14. Subject has undergone replacement surgery of the treatment knee

15. Presence of surgical hardware or other foreign bodies in the treatment knee

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Snibbe Orthopedics	Los Angeles	California	United States	90048
2	University of Miami/Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
3	Brigham & Women's Hospital	Boston	Massachusetts	United States	02115
4	Hermann Drive Surgical Hospital	Houston	Texas	United States	77004

Sponsors and Collaborators

• Sorrento Therapeutics, Inc.

Investigators

• Study Director: Monica Luchi, MD, Sorrento Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sorrento Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03542838
• Other Study ID Numbers: PTVA OA-001
• First Posted: May 31, 2018
• Last Update Posted: Apr 1, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee

Study Results

No Results Posted as of Apr 1, 2021