Symptoms and General Pathology

All Conditions

Neoplasms

Musculoskeletal Diseases

Nervous System Diseases

Skin and Connective Tissue Diseases

Pain

Neuroma

Morton Neuroma

Nerve Sheath Neoplasms

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Metatarsalgia

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Analgesics

Anesthetics

Bupivacaine

Anesthetics, Local

Analgesics, Non-Narcotic

An injection of 1-2 ml bupivacaine 0.5% will be placed around the affected branch of the neuroma (aiming at its proximal end) and dorsal adjacent tissue including the skin dorsally to the neuroma. This is to prevent pain caused by any microscopic spills of RTX during the. A second local anesthetic depot will be placed 1-2 cm proximally to the injection site around the affected branch of the plantar nerve to prevent pain caused by passive current transmission by axonal RTX excitation. Following the course of the affected nerve branch and ultra-sound visualization of the injection site, 0.5-2 ml bupivacaine 0.5% will be injected perineurally. Once the site has sufficient nerve block, the required RTX dose in a solution of 0.25 ml will be injected directly proximal to the Morton s neuroma under ultra-sound visualization.

Resiniferatoxin

Tracy S Williams, R.N.

Andrew J Mannes, M.D.

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Morton s neuroma is an irritation of the nerves that affect the feet. People with this condition may have burning or shooting pain in the balls of their feet. They may also have numbness in adjacent areas. These symptoms may become more frequent and severe over time. The pain may become permanent. Current treatments tend to be short-lived, and they do not work in all people. Better treatments are needed.

Objective:

To test a study drug, resiniferatoxin (RTX), in people with Morton s neuroma.

Eligibility:

Healthy people aged 18 and older who have Morton s neuroma and have tried other standard treatments that did not ease their pain.

Design:

Participants will be involved in the study up to 4 months.

They will be screened. They will have a physical exam with blood tests. They will have a test of their heart function. They will have X-rays of their affected feet. They will have tests to assess their pain and how their feet react to touch and changes in temperature. They will complete questionnaires about their pain.

RTX is injected into the foot at the site of the nerve pain. Participants will receive a shot to numb the area before the RTX is administered. They will be monitored in the clinic for 4 hours after they receive the RTX.

Participants will receive up to 5 follow-up phone calls per week. Each call will take 5 to 10 minutes. They will be asked about their foot pain and whether they have had any side effects from the RTX.

Participants will return to the clinic 4 weeks after the treatment. Previous tests will be repeated.

Study Description:

This is an interventional protocol to determine the safety and tolerability of resiniferatoxin (RTX) for treatment of pain from Morton's neuroma with a single ultrasound-guided perineural injection of (RTX). It is hypothesized that RTX will provide a long-lasting reduction of the intensity of spontaneous and evoked pain and improve daily function without interfering with other sensory modalities or motor function. The safety and efficacy of the interventional procedure will be assessed during the trial. The 3+3 design of RTX treatment will be used to assess safety and determine the Dose Limiting Toxicity (DLT). Pre- and post-procedure pain intensity assessments, including graded interference of pain with daily function and graded descriptors of neuropathic pain, will be performed to assess efficacy. This protocol is intended to test RTX as a new method for long-term relief of refractory Morton s neuroma pain. Potentially this new treatment will reduce the need for radical procedures to treat unrelenting Morton s neuroma pain.

Objectives:

Primary Objective:

-To determine the safety and tolerability of resiniferatoxin (RTX) for treatment of pain from Morton's neuroma.

Secondary Objective:

-To determine the efficacy of RTX intervention on pain intensity, interference of pain with daily function and incidence and intensity of neuropathic qualities of pain.

Endpoints:

Primary Endpoint:

-The number of related Adverse Events (Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials) experienced between day 0 (injection day) and day 28 post-injection.

Secondary Endpoints:

* Change in average worst pain (NRS) between day 21 and day 28 compared to baseline average worst pain.
* Change in pain interference on day 28 compared to screening (preinjection) using PROMIS pain tools.

Change in neuropathic pain score on day 28 compared to screening (preinjection)using painDETECT.

Resiniferatoxin for the Management of Refractory Morton s Neuroma Pain

Phase I Open Label Clinical Trial Using Resiniferatoxin, A Non-Opioid Medication, For the Management of Refractory Morton's Neuroma Pain

-The number of related Adverse Events (Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials) experienced between day 0 (injection day) and day 28 post-injection

Change in average worst pain (NRS) between day 21 and 28 compared to baseline average worst pain (NRS)

Change in pain interference on day 28 compared to screening (pre-injection) using BPI-SF

Change in neuropathic pain score on day 28 compared to screening (pre-injection) using painDETECT

National Institutes of Health Clinical Center (CC)

Cancer Pain

Pain, Intractable

Epidural injection of 1.5mL/min RTX under the guidance of epidurogram.

single dose (0.4, 1, 2, 4, 8,15, 25 or 35 mcg), epidural injection

Monica Luchi, MD

The study is a multicenter, open-label Phase 1b single dose escalation safety study for adult subjects with intractable pain associated with cancer in any area below the mid-thoracic level who meet all other eligibility criteria.

All subjects who received RTX will be included in the analyses and summaries of safety, efficacy, PD, and PK assessments.

The design uses a traditional "3+3" rule-based design that does not stipulate any prior assumption of the dose-toxicity curve. Dose escalation is permitted between successive cohorts based upon a specified algorithm, using discrete dosage steps.

Study to Evaluate Safety and MTD of Epidural Resiniferatoxin Injection for Treatment of Intractable Cancer Pain

A Multicenter, Open-Label, Phase 1b Study to Assess the Safety and Define the Maximally Tolerated Dose of Epidural Resiniferatoxin Injection for the Treatment of Intractable Pain Associated With Cancer

Consumption of analgesics compared to baseline

Quality of life compared to baseline by the total score

Patient-reported rating of improvement on a 7-point scale, ranking the improvement from (1) to (7), with (1) being no change or worse to (7) being a great deal better and a considerable improvement that has made all the difference.

A 11-point scale for rating average and worst pain at the location intended to be treated with RTX within 12 hours of the clinical visit, with 0 being no pain to 10 being worst pain imaginable.

Quality of life affected by pain at the location intended to be treated with RTX, each question rates pain level and pain interference on a 0 to 10 scale. For pain level questions, 0 represents no pain and 10 represents pain as bad as can be imagined. For pain interference questions, 0 is "does not interfere" and 10 is "completely interferes".

Grade 3 or 4 Toxicity associated with RTX administration

Maximum dose without a Grade 3 or 4 toxicity

Daily average pain and daily worst pain on a 0-10 scale

Sorrento Therapeutics, Inc.

15 mcg, 20 mcg, or 25 mcg in 2mL injected once into the epidural space

2mL injected once into the epidural space

Resiniferatoxin is a compound purified from natural sources

Placebo

Mike Royal, MD

This Phase 2 study assesses the safety and efficacy of a single injection of Resiniferatoxin versus placebo for the treatment of intractable advanced cancer pain.

This is a global multicenter, randomized Phase 2 study for subjects with advanced cancer experiencing intractable pain to assess the safety and efficacy of a single epidural injection of Resiniferatoxin versus vehicle control. Additional subjects who elect to not enroll but are willing to be followed will comprise a Concurrent Control Group. Subjects will be followed for twelve months.

Study to Assess Epidural Resiniferatoxin for the Treatment of Intractable Pain Associated With Advanced Cancer

A Multicenter, Phase 2 Study to Assess the Safety and Efficacy of Epidural Resiniferatoxin for the Treatment of Intractable Pain Associated With Advanced Cancer

To assess the safety of epidural RTX including incidence and severity of any short-term and long-term treatment-emergent adverse events (TEAEs) using the Common Terminology Criteria for Adverse Events (CTCAE) criteria

To assess efficacy of each epidural RTX dose in comparison to control groups on the subject's intractable pain due to advanced cancer using the Brief Pain Inventory, Short Form (BPI-SF) score (1-10, with 10 associated with worse pain)

To assess the efficacy of each epidural RTX dose in comparison to control groups on the quality of life using Treatment Helpfulness Questionnaire score (graded 1-7, with 7 being most helpful)

To assess the effect of each epidural RTX dose on opioid consumption, measuring the average reduction compared to baseline of daily opioid consumption, calculated as an oral morphine equivalent dose

Behaviors and Mental Disorders

Quality of Life

Dermatologic Agents

Capsaicin

Schedule a maximum of 3 periganglionic DRG injection(s) at contiguous level(s) to treat targeted DRG responsible for chronic CIBP

Resiniferatoxin (RTX) is an ultrapotent agonist analog of capsaicin that targets a receptor expressed on specific dorsal root sensory ganglia (DRG) neurons and is expected to reduce pain within the targeted zone.

John D Heiss, M.D.

Background:

Cancer-induced bone pain (CIBP) is common in people with cancer. Bone cancer can also lead to anxiety, depression, and reduced mobility and quality of life. Researchers believe a research drug called resiniferatoxin (RTX) may be able to help.

Objective:

To learn whether RTX is safe and can reduce cancer induced bone pain.

Eligibility:

People ages 18 and older with CIBP that is not relieved by standard treatments

Design:

Participants will have up to 6 outpatient visits over about 7 months. These will include:

Medical history

Physical exam

Blood and urine tests.

Thermal testing: a disk placed on the skin to test ability to sense temperature in and around the area of pain

Chest x-ray

EKG: stickers are placed on the chest to measure heart signals

ECG: measures electrical activity of the heart

Participants will have 1 inpatient visit lasting 2-4 days. This will include:

Catheter inserted into a vein in the arm. They are given anesthesia, sedation, and x-ray contrast.

A needle is passed through the skin of the back to inject the RTX.

Participants will keep a log of the pain medications they take after surgery.

Participants will be called 1 week and 2, 3, and 4 months after the injection.

Participants will be mailed surveys and questionnaires to complete 2, 3, and 4 months after the injection.

Cancer-induced bone pain (CIBP) is a common clinical problem. While primary osteosarcoma is relatively uncommon, bone metastases frequently cause cancer-related pain with metastatic spread to bone in 60-84% of cases. Resiniferatoxin (RTX) is an ultrapotent agonist analog of capsaicin that targets a receptor expressed on specific dorsal root sensory ganglia (DRG) neurons and is expected to reduce pain within the targeted zone. The overall program goal is to develop a new treatment for intractable chronic pain below the mid-thoracic level resulting from CIBP that has not been controlled with conservative treatments.

Objectives:

The primary objective it to determine the maximum tolerated dose (MTD) of RTX when injected near one or more DRGs, to characterize its safety/toxicity profile, and to identify any dose-limiting toxicity (DLT). The secondary objectives are to determine the relative change in pain reduction, the change in opioid analgesic consumption and quality of life prior to RTX injection and at the various post RTX timepoints.

Study Population

Up to 30 adult subjects are estimated to be necessary for enrollment to have up to 16 subjects who will receive RTX and provide study-related assessment results through the 30-day time point.

Design

The study is a single center, open-label Phase 1b dose escalation safety and efficacy trial for adult subjects with intractable pain due to CIBP below the mid-thoracic level. Those subjects who meet all inclusion and exclusion criteria will undergo various study procedures and then be scheduled for the unilateral periganglionic (PG) DRG injection(s) (a maximum of 3 contiguous levels) under fluoroscopic guidance to treat the targeted DRGs demonstrated to be responsible for the chronic CIBP. The RTX will be injected at 1 of 4 dose levels, 0.8mcg/DRG, 1.6 mcg/DRG, 3.2 mcg/DRG or 6.4 mcg/DRG. The adaptivedesign algorithm for this study utilizes outcome dependent randomization, a process that selects the dose to be administered to the next subject based on all previous outcomes. In this schema, DLT is the measure that will be used to determine if it is safe to escalate to the next highest dose level.

Subjects who are screen failures and those who prematurely terminate participation will be replaced until 16 subjects have received the injection(s) and completed study-related assessments through the day 30 (D30) timepoint. There is no placebo group because of the invasive nature of the injection and the dose escalation performed in the study.

Outcome Measures

The primary outcome is to achieve a dose-response relationship for safety. All subjects will receive RTX. The secondary outcome measures are: 1) change in NRS and VAS scores at the post-RTX assessments compared to pre RTX assessment, 2) change of opioid usage (in MME) at post RTX assessments compared to pre RTX assessment; 3) comparison SF-36 and BDI at pre RTX injection and Days 14, 37, and 187.

The efficacy outcome variable will be evaluated by establishing dose-response curves, with dose plotted on the x-axis and changes in efficacy endpoints (before RTX treatment and at the post RTX assessment visits) plotted on the y-axis. If, at the end of the study, all dose levels of RTX have equal pain-relieving efficacy, the Data Safety Monitoring Committee (DSMC) may determine if it is appropriate to include a dose lower than 0.8 mcg and/or a control group. On the other hand, if the dose-response curves show that higher doses could result in greater pain-relieving efficacy, the protocol may be amended to include higher doses of RTX.

Periganglionic Resiniferatoxin for the Treatment of Intractable Pain Due to Cancer-induced Bone Pain

An Open-Label, Phase 1b Safety and Efficacy Trial of Periganglionic Resiniferatoxin for the Treatment of Intractable Pain Due to Cancer-induced Bone Pain

.We do plan to share IPD. we will share all IPD that results in a publication on a public repository, as required by most journals. the data will be de-identified and anonymized.

The primary study outcome measures are related to safety and toxicity of the investigational agent. The primary study outcome measures are: DLT MTD of RTX

The average of the daily worst NRS scores will be used throughout the study for post-injection visits.

The BPI is a validated tool designed to assess the severity of pain and the impact of pain on daily functions in patients with cancer pain and pain due to other chronic diseases.

National Institute of Neurological Disorders and Stroke (NINDS)

Single dose of Resiniferatoxin (25 mcg in 3 mL) injected epidurally

Standard of care treatment as determined by the investigator

Resiniferatoxin is a TRPV-1 agonist which works by specifically ablating nociceptive nerve fibers.

Standard of care for intractable pain with the exception of intra-thecal pump placement as determined by the investigator.

Standard of Care

This is a Phase 3 study to assess the safety and efficacy of a single epidural administration of Resiniferatoxin versus standard of care for the treatment of intractable pain associated with cancer.

This study is a multicenter, randomized Phase 3 study to assess the safety and efficacy of a single epidural administration of Resiniferatoxin versus standard of care (SOC) for the treatment of intractable pain associated with cancer. Subjects will be followed for 12 weeks after treatment.

Follow-up visit examinations will be performed by a blinded outcomes assessor.

Phase 3 Study to Assess Resiniferatoxin vs Standard of Care for the Treatment of Intractable Cancer Pain

A Multicenter, Randomized, 2-Arm, Phase 3 Study to Assess the Efficacy and Safety of a Single Epidural Administration of Resiniferatoxin Versus Standard of Care (SoC) for the Treatment of Intractable Pain Associated With Cancer

Change from baseline to Week 4 in the intensity of worst pain over the previous 24 hours in the area targeted for treatment as measured by the 11-point NPRS (0-10 where 0 is no pain and 10 is worst pain imaginable)

Change from baseline to Weeks 8 and 12 in the intensity of worst pain over the previous 24 hours in the area targeted for treatment as measured by the 11-point NPRS (0-10 where 0 is no pain and 10 is worst pain imaginable)

AUC calculated on change from baseline through Week 4 in worst pain in the target pain location over the previous 24 hours, using the NPRS (0-10)

Incidence and severity of AEs assessed using the Common Terminology Criteria for Adverse Events (CTCAE) criteria

Change in Quality of Life from baseline to week 4 based on total score from the BPI-SF, modified to record the target pain treated with study drug

Duration of response defined as time from ≥20% decrease from baseline in worst pain score in the target pain location to ≥20% increase from the nadir of the worst pain score

Change from baseline to Week 4 in the intensity of average pain over the previous 24 hours in the target pain location as measured by the NPRS (0-10)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Resiniferatoxin for the Management of Refractory Morton s Neuroma Pain	NCT05695339	Morton's Neurom...	Resiniferatoxin	18 Years -	National Institutes of Health Clinical Center (CC)
Resiniferatoxin for the Management of Refractory Morton s Neuroma Pain	NCT05695339	Morton's Neurom...	Resiniferatoxin	18 Years -	National Institutes of Health Clinical Center (CC)
Resiniferatoxin for the Management of Refractory Morton s Neuroma Pain	NCT05695339	Morton's Neurom...	Resiniferatoxin	18 Years -	National Institutes of Health Clinical Center (CC)
Study to Evaluate Safety and MTD of Epidural Resiniferatoxin Injection for Treatment of Intractable Cancer Pain	NCT03226574	Intractable Can...	Resiniferatoxin	18 Years -	Sorrento Therapeutics, Inc.
Study to Assess Epidural Resiniferatoxin for the Treatment of Intractable Pain Associated With Advanced Cancer	NCT05067257	Pain, Intractab... Pain Cancer Pain	Resiniferatoxin Placebo	18 Years -	Sorrento Therapeutics, Inc.
Study to Evaluate Safety and MTD of Epidural Resiniferatoxin Injection for Treatment of Intractable Cancer Pain	NCT03226574	Intractable Can...	Resiniferatoxin	18 Years -	Sorrento Therapeutics, Inc.
Study to Assess Epidural Resiniferatoxin for the Treatment of Intractable Pain Associated With Advanced Cancer	NCT05067257	Pain, Intractab... Pain Cancer Pain	Resiniferatoxin Placebo	18 Years -	Sorrento Therapeutics, Inc.
Periganglionic Resiniferatoxin for the Treatment of Intractable Pain Due to Cancer-induced Bone Pain	NCT02522611	Intractable Pai... Palliative Care	Resiniferatoxin	18 Years - 150 Years	National Institutes of Health Clinical Center (CC)
Periganglionic Resiniferatoxin for the Treatment of Intractable Pain Due to Cancer-induced Bone Pain	NCT02522611	Intractable Pai... Palliative Care	Resiniferatoxin	18 Years - 150 Years	National Institutes of Health Clinical Center (CC)
Phase 3 Study to Assess Resiniferatoxin vs Standard of Care for the Treatment of Intractable Cancer Pain	NCT04572776	Pain, Intractab... Pain Cancer	Resiniferatoxin Standard of Car...	18 Years -	Sorrento Therapeutics, Inc.

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