Study to Evaluate Intra-articular Resiniferatoxin to Treat Moderate to Severe Pain From Knee Osteoarthritis

A Phase 2, Randomized, Active and Placebo-Controlled, Dose Ranging Study to Evaluate the Efficacy and Safety of Intra-articular Resiniferatoxin to Treat Moderate to Severe Pain From Knee Osteoarthritis

This study evaluates the efficacy and safety of a single IA injection of various RTX doses, Zilretta or placebo for the treatment of pain due to moderate to severe osteoarthritis knee pain..

Study Overview

• Status: Active, not recruiting
• Conditions: Knee Osteoarthritis; Osteoarthritis, Knee; Knee Pain Chronic
• Intervention / Treatment: Drug: Placebo; Drug: Resiniferatoxin; Drug: Zilretta

Detailed Description

This study is a multi-center, Phase 2, randomized, dose ranging, assessor-blinded, active and placebo-controlled, parallel-group prospective study evaluating the efficacy and safety of a single IA injection of various RTX doses, Zilretta or placebo for the treatment of pain due to moderate to severe osteoarthritis knee pain.

A planned 112 subjects will be randomized to one of 7 groups (n=16 each) with each subject receiving one IA injection in the index knee joint (the knee primarily affected by pain if bilateral).

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Mesa, California, United States, 91942
      • Horizon Clinical Research
    • Pasadena, California, United States, 91105
      • Lotus Clinical Research
  • Illinois
    • Oak Brook, Illinois, United States, 60523
      • Affinity Health
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Advance Pain
  • Texas
    • Bellaire, Texas, United States, 77401
      • HD Research LLC
    • Carrollton, Texas, United States, 75006
      • HD Research LLC

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• BMI < 50 kg/m
• Have moderate-to-severe pain in the index knee due to osteoarthritis (OA) as assessed by the investigator, based on American College of Rheumatology criteria
• Have had OA pain duration in the index knee ≥ 6 months prior to Screening
• Reports worst daily average pain with walking of ≥ 4 on the 0 to 10 NRS for pain intensity during the week prior to Screening
• Have a knee x-ray or MRI scan with KL grade ≥ 2 in the index knee based upon radiographic images obtained within 3 months prior to Screening (image must be available for review)
• Have had treatment failure with at least two prior analgesic agents (at least one NSAID) defined as discontinuation due to side effects or inadequate response to treatment
• Willing to abstain from other IA injections or knee surgery for at least 6 months after study treatment unless elects early discontinuation from the study
• Able to comply with the study procedures and give informed consent
• If on any analgesic medications, have been taking a stable dose for at least one month prior to screening with no increase in dose leading up to study treatment. Note that if the subject is on "as needed" or PRN analgesic medications, these may be continued during the study
• Willing to follow contraception guidelines

Exclusion Criteria:

• Have a history of a hemorrhagic event that is CTCAEv5 Grade 2 or higher within the 6 months prior to screening
• Have evidence of or history of a serious coagulopathy or hemostasis problem at Screening or Baseline
• Have had an IA injection in the index knee within one month prior to screening (3 months if prior IA injection with Zilretta)
• Have undergone arthroscopic or open surgery or replacement surgery to the index knee within 6 months of screening
• Have surgical hardware or other foreign bodies within the index knee joint
• Have current instability/misalignment in the index knee post repair
• Have a sensory peripheral neuropathy that is CTCAEv5 Grade 2 or higher involving the index leg at Screening
• Have significant pain in other joints or body locations that make it difficult to assess pain in the index knee
• If on opioid analgesics to treat knee OA, have an upper limit of 30 mg/day as converted to an oral morphine equivalent dose
• Have a history of substance abuse
• Have an allergy or hypersensitivity to capsaicin, chili peppers, lidocaine or resiniferatoxin
• Pregnant at Screening or planning on becoming pregnant or currently breastfeeding
• Have had a non-study related minor surgical procedure ≤ 3 days or major surgical procedure ≤ 14 days prior to Screening and must be sufficiently recovered and stable prior to study treatment
• Have 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Resiniferatoxin; 7.5 mcg, 10 mcg, 12.5 mcg, 15 mcg, or 20 mcg in 5 mL injected once intra-articularly	Drug: Resiniferatoxin; Resiniferatoxin is a compound purified from natural sources.; Other Names: RTX
Active Comparator: Zilretta; 32 mg in 5 mL injected once intra-articularly	Drug: Zilretta; Zilretta is an extended-release corticosteroid approved to manage osteoarthritis knee pain.; Other Names: triamcinolone acetonide
Placebo Comparator: Placebo; 5 mL injected once intra-articularly	Drug: Placebo; Vehicle solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Worst Average Daily Pain at Week 26	Change from baseline through Week 26 in the weekly mean of Worst Average Daily Pain in the previous 24 hours with walking (WADP) using the Numerical Rating Scale of pain intensity, 0-10 scale (NRS)	Baseline to Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response	Time to return to within 10% of baseline pain score with walking based on the weekly mean WADP scores using the NRS (0-10)	Baseline through end of study at Week 52
Change in Worst Average Daily Pain at Week 12	Change from baseline through Week 12 in the weekly mean of Worst Average Daily Pain in the previous 24 hours with walking (WADP) using the Numerical Rating Scale of pain intensity, 0-10 scale (NRS).	Baseline to Week 12
Change in quality of life	Change from baseline to Week 26 in the Knee Injury and Osteoarthritis Outcome Score (KOOS) Quality of Life (QoL) subscale	Baseline to Week 26
Change in WOMAC score	Change from baseline to Week 12 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score (WOMAC-TW12) and subscale scores	Baseline to Week 12

Collaborators and Investigators

• Sponsor: Sorrento Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): November 1, 2023

Study Registration Dates

• First Submitted: May 10, 2021
• First Submitted That Met QC Criteria: May 10, 2021
• First Posted (Actual): May 13, 2021

Study Record Updates

• Last Update Posted (Estimate): January 16, 2023
• Last Update Submitted That Met QC Criteria: January 12, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: osteoarthritis; knee; knee pain
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
• Other Study ID Numbers: RTX-OAK-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No