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

Sponsor

Sorrento Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04885972

Collaborator

(none)

112

Enrollment

Locations

Arms

23.5

Anticipated Duration (Months)

18.7

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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..

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis, Knee Knee Osteoarthritis Knee Pain Chronic	Drug: Resiniferatoxin Drug: Zilretta Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

112 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 15, 2021

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in Worst Average Daily Pain at Week 26 [Baseline to 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)

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Horizon Clinical Research	La Mesa	California	United States	91942
2	Lotus Clinical Research	Pasadena	California	United States	91105
3	Affinity Health	Oak Brook	Illinois	United States	60523
4	Advance Pain	Edgewood	Kentucky	United States	41017
5	HD Research LLC	Bellaire	Texas	United States	77401
6	HD Research LLC	Carrollton	Texas	United States	75006