Resiniferatoxin + Zilretta for Osteoarthritis

Not currently recruiting at 5 trial locations

Overseen By Mike Royal, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sorrento Therapeutics, Inc.

Must not be taking: Opioids, others

Disqualifiers: Hemorrhagic events, Coagulopathy, Surgery, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 53

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well a one-time injection of either Resiniferatoxin (RTX) or Zilretta relieves moderate to severe knee pain from osteoarthritis. Researchers aim to determine if these treatments can safely and effectively reduce pain compared to a placebo (a treatment with no active drug). Individuals with knee osteoarthritis for at least six months who have tried at least two unsuccessful pain relief methods might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on any pain medications, you should have been on a stable dose for at least one month before the study and can continue 'as needed' pain medications during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Resiniferatoxin (RTX) has been tested in various situations, but its safety profile remains incomplete. Some studies suggest it can be harmful if swallowed and might irritate the skin and eyes. However, in animal studies, RTX was generally safe, with only minor side effects like a faster heartbeat.

For Zilretta, an approved treatment for knee pain, studies indicate it is usually well-tolerated. Common side effects include joint pain, swelling, and minor issues like sinus infections and coughs, occurring in a small number of patients.

Overall, while Zilretta has a more established safety record, the safety of RTX in humans is still under investigation. Participants should consider these factors when deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about resiniferatoxin for knee osteoarthritis because it offers a novel approach to pain management. Unlike traditional treatments like NSAIDs or corticosteroids, resiniferatoxin targets and desensitizes nerve fibers that transmit pain, potentially providing longer-lasting relief. This treatment is derived from a natural compound found in chili peppers, which allows for a potent effect with a single intra-articular injection. Its unique mechanism of action and delivery could offer significant benefits over current therapies.

What evidence suggests that this trial's treatments could be effective for osteoarthritis knee pain?

Research has shown that resiniferatoxin (RTX), one of the treatments in this trial, can greatly reduce knee pain from osteoarthritis. In some studies, patients who received RTX injections reported a pain reduction of more than 70%. This relief can last up to six months, offering a long-lasting option for managing pain.

Zilretta, another treatment option in this trial, is an FDA-approved treatment that provides quick and lasting relief for knee osteoarthritis pain. Many patients experience little to no pain just one week after the injection. This trial evaluates both treatments as promising options for those suffering from knee osteoarthritis pain. ^{6 7 8 9 10}

Who Is on the Research Team?

Mike Royal, MD

Principal Investigator

Sorrento Therapeutics, Inc.

Are You a Good Fit for This Trial?

Inclusion Criteria

BMI < 50 kg/m

Willing to follow contraception guidelines

You have significant knee pain caused by osteoarthritis, as determined by your doctor using specific guidelines from the American College of Rheumatology.

Exclusion Criteria

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)

If on opioid analgesics to treat knee OA, have an upper limit of 30 mg/day as converted to an oral morphine equivalent dose

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intra-articular injection of either Resiniferatoxin, Zilretta, or placebo in the index knee joint

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

Multiple visits (in-person and virtual) over 52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Resiniferatoxin
• Zilretta

How Is the Trial Designed?

Group I: Resiniferatoxin Experimental Treatment 1 Intervention

7.5 mcg, 10 mcg, 12.5 mcg, 15 mcg, or 20 mcg in 5 mL injected once intra-articularly

Group II: Zilretta Active Control 1 Intervention

32 mg in 5 mL injected once intra-articularly

Group III: Placebo Placebo Group 1 Intervention

5 mL injected once intra-articularly

Who Is Running the Clinical Trial?

Sorrento Therapeutics, Inc.

Lead Sponsor

Trials

48

Recruited

2,000+

Published Research Related to This Trial

Resiniferatoxin (RTX) selectively ablates nociceptive neurons expressing the vanilloid receptor 1 (VR1), effectively reducing high-intensity pain perception and neurogenic inflammation in Rhesus monkeys without affecting normal touch sensation or motor function.

The study demonstrated that RTX infusion into the trigeminal ganglia led to significant reductions in pain responses (e.g., eye blinks and squinting) while showing no neurological deficits or toxicity, suggesting its potential as a treatment for pain syndromes like trigeminal neuralgia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective ablation of nociceptive neurons for elimination of hyperalgesia and neurogenic inflammation. Tender, GC., Walbridge, S., Olah, Z., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40776673/

Intraarticular resiniferatoxin, a potent TRPV1 agonist, for ... It makes the nerves stop sending pain signals. The result is less pain. One shot of RTX lasts a long time, as much as half a year. RTX does not ...

2. oarsijournal.com oarsijournal.com/article/S1063-4584(20)30295-8/fulltext

Preliminary results from a phase 1b double-blind study to ... Compared to baseline pain by WOMAC A1, >70% reduction in the pain was achieved in 50% of pooled RTX-treated subjects and in 83% of the subjects at the 12.5 mcg ...

3. ard.bmj.com ard.bmj.com/content/83/Suppl_1/667.2

POS1153 PRELIMINARY EVALUATION OF THE SAFETY ... Consistent with these data, the RTX 0.5 mg and 2 mg treatment groups showed a greater reduction in WOMAC total and subscale scores (pain, physical function and ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04885972

Study to Evaluate Intra-articular Resiniferatoxin to Treat ... 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 ...

5. tandfonline.com tandfonline.com/doi/full/10.1080/17581869.2025.2535271

Intraarticular resiniferatoxin, a potent TRPV1 agonist, for ... So far, all of the trials suggest that intraarticular administration of RTX is a safe and highly effective, long-duration treatment for osteoarthritis pain. 2.

6. caymanchem.com caymanchem.com/msdss/11349m.pdf?srsltid=AfmBOopOSXF0UfRpoph7Zux67JuKo0qKc-a5cbzttisivn6cAxk7UiLs

Resiniferatoxin SAFETY DATA SHEET Section 2. Hazards ... Toxic if swallowed. To the best of our knowledge, the toxicological properties have not been thoroughly investigated. Adverse Human Health.

7. chemicalbook.com chemicalbook.com/msds/resiniferatoxin.pdf

RESINIFERATOXIN - Safety Data Sheet Hazard statement(s). H301 Toxic if swalloed. H314 Causes severe skin burns and eye damage. H315 Causes skin irritation. H319 Causes serious eye irritation.

8. fishersci.com fishersci.com/store/msds?partNumber=AC328470010&countryCode=US&language=en

SAFETY DATA SHEET Corrosive solid, toxic, n.o.s.. Technical Name. Resiniferatoxin (high purity). Hazard Class. 8. Subsidiary Hazard Class. 6.1. Packing Group.

9. neb.com neb.com/en-sg/-/media/0e8ca68566ea421098816d7fa637fdd3.pdf?srsltid=AfmBOor3dHL1v1S3_FsHDWuQnsSnB0rUVJA0FOsvx_qPA1ffzldvBn7W

Safety Data Sheet for RTX WarmStart (M0380) Component Information. Delayed and immediate effects as well as chronic effects from short and long-term exposure. Skin corrosion/irritation. No ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9878299/

Safety and efficacy of intravesical instillation ... Application of RTX in the feline urinary bladder was well tolerated at all doses tested in this study. The only adverse effect noted was an increase in heart ...