VX-993 for Acute Pain

No longer recruiting at 13 trial locations

Overseen By Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vertex Pharmaceuticals Incorporated

Must not be taking: Anti-arrhythmia treatments

Disqualifiers: Foot surgery, Cardiac dysrhythmias, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new drug, VX-993, in reducing acute pain after bunion surgery. Researchers aim to compare the efficacy and safety of VX-993 with a common pain reliever, hydrocodone/acetaminophen, and a placebo. Individuals scheduled for a specific type of bunion surgery, known as an Austin procedure, and who have not undergone foot surgery before, may qualify. Participants will receive either VX-993, the standard pain medication, or a placebo to determine which best manages pain. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that VX-993 is generally safe and well tolerated. In earlier studies, most side effects were mild to moderate, and no serious side effects were reported. While some individuals might experience minor discomfort, VX-993 has not caused any major health issues in the trials so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute pain?

Most treatments for acute pain, like hydrocodone bitartrate/acetaminophen (HB/APAP), work by blocking pain signals in your brain. But VX-993 is unique because it targets the pain at its source with a different mechanism, potentially offering pain relief without the side effects associated with opioids. Researchers are excited about VX-993 because it could provide a safer alternative to traditional painkillers, reducing the risk of addiction and other adverse effects.

What evidence suggests that VX-993 might be an effective treatment for acute pain?

This trial will compare VX-993, an investigational treatment, with hydrocodone bitartrate/acetaminophen (HB/APAP) and a placebo. Research has shown that VX-993 did not reduce sudden pain. In earlier studies, VX-993 was no more effective at managing pain than a placebo, which contains no active medicine. Although this treatment aimed to block pain signals, it did not surpass current options. Consequently, the development of VX-993 for treating sudden pain has been discontinued. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for individuals scheduled to have a bunionectomy (a type of foot surgery) using regional anesthesia. Participants must be able to follow instructions and adhere to pain management guidelines before and after the procedure.

Inclusion Criteria

I followed all pain management instructions after my bunion surgery.

I am scheduled for a bunion surgery on one foot with a specific technique.

I am mentally alert and can follow instructions.

Exclusion Criteria

I had surgery for a severe foot deformity or complications during bunion surgery.

I have had surgery on my foot before.

I have had heart rhythm problems treated in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive randomized doses of VX-993, HB/APAP, or placebo to evaluate efficacy and safety for acute pain after bunionectomy

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• VX-993

Trial Overview

The study tests VX-993's effectiveness in managing acute pain post-bunionectomy, comparing it with HB/APAP (likely a standard painkiller) and placebos that match each drug. It also assesses safety, tolerability, and how the body processes VX-993.

How Is the Trial Designed?

Group I: VX-993 Experimental Treatment 2 Interventions

Participants will be randomized to receive different dose levels of VX-993.

Group II: Hydrocodone bitartrate/acetaminophen (HB/APAP) Active Control 2 Interventions

Participants will be randomized to receive HB/APAP.

Group III: Placebo Placebo Group 2 Interventions

Participants will be randomized to receive placebo matched to VX-993 and HB/APAP.

Who Is Running the Clinical Trial?

Vertex Pharmaceuticals Incorporated

Lead Sponsor

Trials

267

Recruited

36,100+

Dr. David Altshuler

Vertex Pharmaceuticals Incorporated

Chief Medical Officer since 2020

MD, PhD

Dr. Reshma Kewalramani

Vertex Pharmaceuticals Incorporated

Chief Executive Officer since 2020

MD, trained in internal medicine and nephrology

Published Research Related to This Trial

This rapid review analyzed 15 studies involving 1043 patients with monkeypox virus (MPXV) to summarize pain management strategies, highlighting that severe pain is a common reason for medical attention and hospital admission.

Proposed treatments for managing pain associated with MPXV include acetaminophen, ibuprofen, opioids, and topical options like lidocaine gel, indicating a need for clearer guidelines to optimize pain management and reduce patient morbidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pain Associated With Monkeypox Virus: A Rapid Review. Hallo-Carrasco, A., Hunt, CL., Prusinski, CC., et al.[2023]

Vanilloid agonists like resiniferatoxin (RTX) provide effective conduction analgesia by selectively targeting pain-related nerve fibers (C- and ADelta-fibers) without affecting other sensory or motor functions, making them a promising alternative to traditional local anesthetics.

In rat studies, RTX demonstrated long-lasting pain relief with minimal nerve damage compared to lidocaine, suggesting a wider therapeutic window and potential for clinical use, although initial pain from RTX application requires a local anesthetic to mitigate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vanilloid-induced conduction analgesia: selective, dose-dependent, long-lasting, with a low level of potential neurotoxicity. Kissin, I.[2022]

The increasing-temperature hot plate (ITHP) method effectively measures the noxious heat threshold in unrestrained rats, showing consistent results over time, which is important for evaluating pain responses.

Morphine, diclofenac, and paracetamol were found to significantly elevate the heat threshold, indicating their analgesic efficacy, while the VR1 receptor agonist resiniferatoxin (RTX) induced a notable drop in heat threshold, demonstrating its potential to model heat allodynia and sensitivity to pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of resiniferatoxin on the noxious heat threshold temperature in the rat: a novel heat allodynia model sensitive to analgesics. Almási, R., Pethö, G., Bölcskei, K., et al.[2018]

In a rat model, perineural administration of resiniferatoxin (RTX) completely prevented hyperalgesia (increased sensitivity to pain) following an incision, demonstrating its efficacy in managing postoperative pain.

RTX effectively blocked pain responses without affecting nonpainful sensations or motor functions, indicating a potential for safe pain management in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perineural resiniferatoxin prevents hyperalgesia in a rat model of postoperative pain. Kissin, I., Davison, N., Bradley, EL.[2021]

In a study involving C57BL6 male mice with chronic inflammatory arthritis induced by Complete Freund's Adjuvant, intra-articular injections of capsaicin (CAP) and resiniferatoxin (RTX) significantly improved evoked pain scores (EPS), indicating a reduction in pain perception.

However, while CAP and RTX improved EPS, they did not enhance automated dynamic weight bearing (ADWB) measures, suggesting that these treatments may alleviate pain without affecting the overall weight distribution on the affected limb.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Treatment with Resiniferatoxin and Capsaicin on Dynamic Weight Bearing Measures and Evoked Pain Responses in a Chronic Inflammatory Arthritis Murine Model. Bert, J., Mahowald, ML., Frizelle, S., et al.[2019]

Citations

1.

investors.vrtx.com

investors.vrtx.com/news-releases/news-release-details/vertex-announces-results-phase-2-study-vx-993-treatment-acute

Vertex Announces Results from Phase 2 Study of VX-993 ...

Treatment with VX-993 did not result in a statistically significant improvement on the primary endpoint of the time-weighted Sum of the Pain ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06619847

A Study Evaluating Efficacy and Safety of VX-993 for Acute ...

A sponsor or investigator who submits a certification can delay results submission up to 2 years after the certification/extension first submitted date, unless ...

3.

neurologylive.com

neurologylive.com/view/nav1-8-pain-signal-inhibitor-vx-993-fails-show-efficacy-phase-2-trial-acute-pain

NaV1.8 Pain Signal Inhibitor VX-993 Fails to Show Efficacy ...

Vertex Pharmaceuticals halts VX-993 development for acute pain after phase 2 trial shows no significant efficacy compared with placebo.

4.

appliedclinicaltrialsonline.com

appliedclinicaltrialsonline.com/view/vertex-selective-nav1-8-inhibitor-falls-short-acute-pain-clinical-trial

Vertex's Selective NaV1.8 Inhibitor Falls Short in Acute ...

VX-993 failed to demonstrate superior efficacy over existing NaV1.8 inhibitors, leading to its discontinuation as monotherapy for acute pain.

5.

fiercebiotech.com

fiercebiotech.com/biotech/vertex-drops-journavx-follower-acute-pain-after-complete-phase-2-failure

Vertex drops asset in acute pain after phase 2 fail

All three dose levels of Nav1.8 inhibitor VX-993 failed to improve pain intensity over a 48-hour period compared to placebo.

6.

clinicaltrialsarena.com

clinicaltrialsarena.com/news/vertex-pharmaceuticals-phase-ii-pain-trial-results/

Vertex's Journavx successor culled in acute pain after ...

Topline results reveal that VX-993 did not meet its primary endpoints, meaning Vertex will discontinue its development in acute pain.