VNX001 for Painful Bladder Syndrome

Recruiting at 4 trial locations

Overseen By Vaneltix Pharma, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vaneltix Pharma, Inc.

Must not be taking: Antidepressants, Anticonvulsants, St. John's Wort

Disqualifiers: Pregnancy, Neurogenic bladder, CNS disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 8

Duration: 14 days

50 Participants Needed

Trial Summary

Do I need to stop taking my current medications for the trial?

The trial does not specify if you need to stop all current medications, but certain medications are prohibited. You cannot take phenytoin, carbamazepine, St. John's Wort, phenobarbital, or rifampin. If you are on a tricyclic antidepressant or a GABA analogue like gabapentin or pregabalin, you must be on a stable dose for at least 3 weeks.

Is VNX001 safe for humans?

Vanilloid receptor agonists like capsaicin and resiniferatoxin, which may be similar to VNX001, have been studied for bladder conditions. While they show some promise, larger studies are needed to confirm their safety and effectiveness, as current data is not strong enough to recommend routine use. ^{1 2 3 4 5}

How does the drug VNX001 differ from other treatments for Painful Bladder Syndrome?

VNX001 is unique because it targets the TRPV1 receptor, which is involved in bladder pain and hypersensitivity. This approach is different from other treatments as it aims to desensitize the nerve fibers responsible for pain, potentially offering relief by reducing the bladder's overactive response to stimuli. ^{2 6 7 8 9}

What is the purpose of this trial?

This is an open-label study that will enroll participants with Interstitial Cystitis / Bladder Pain Syndrome (IC/BPS). The study will assess PRN (as needed) dosing of up to 6 intravesical (via catheter) doses of VNX001 (study drug) to treat acute instances of moderate to severe bladder pain over a 14-day period. The main aim of the study is to tally the number of doses and assess pain before and after doses. The study will review the safety and tolerability of VNX001. Participants will need to attend up to seven (7) clinic visits (1 for screening and up to 6 visits for VNX001 dosing) or at least one (1) clinic visit (for a combined screening/dosing visit) and 5 telephone visits over the course of 14 days. Participants will also be asked complete a diary or telephone call each day of the study, in order to record bladder pain, urinary urgency, side effects, and medications taken.

Eligibility Criteria

This trial is for individuals who have completed Study VNX001-111 and suffer from Interstitial Cystitis / Bladder Pain Syndrome (IC/BPS). It's designed to help those with moderate to severe bladder pain by testing a new treatment called VNX001.

Inclusion Criteria

I completed Study VNX001-111 and meet all other requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive up to 6 intravesical doses of VNX001 over 14 days to treat acute bladder pain

14 days

Up to 6 visits (in-person) or 1 combined visit (in-person) and 5 telephone visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 days

1 follow-up call

Treatment Details

Interventions

• VNX001

Trial Overview The study tests the safety and effectiveness of up to six doses of VNX001, administered directly into the bladder over two weeks. Participants will track their pain levels before and after each dose, as well as any side effects.

Participant Groups

Group I: Open Label Arm Experimental Treatment 1 Intervention

VNX001 intravesical administration PRN up to 6 doses over 14 days. The VNX001 effective dose is 15 mL of buffered lidocaine HCl (200 mg) and sodium heparin (50,000 USPU).

Who Is Running the Clinical Trial?

Vaneltix Pharma, Inc.

Lead Sponsor

Trials

2

Recruited

170+

Prevail Infoworks, Inc

Collaborator

Trials

4

Recruited

1,000+

Prevail Infoworks

Industry Sponsor

Findings from Research

Capsaicin and resiniferatoxin (RTX) show potential as treatments for neurogenic bladder, but more extensive studies are necessary to confirm their effectiveness and safety.

Currently, vanilloid receptor agonists are not recommended for routine use in overactive bladder or interstitial cystitis due to insufficient evidence of efficacy and concerns about the risks associated with catheterization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of vanilloids in urologic disorders. Foster, HE., Lake, AG.[2019]

In women with sensory urgency (SU), there is a significant increase in TRPV1 mRNA expression in the trigonal mucosa of the bladder, suggesting a potential role of TRPV1 in bladder hypersensitivity.

In contrast, patients with idiopathic detrusor overactivity (IDO) showed no differences in TRPV1 expression between trigonal and body mucosa, indicating that TRPV1 may not be involved in IDO-related symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The molecular basis of urgency: regional difference of vanilloid receptor expression in the human urinary bladder. Liu, L., Mansfield, KJ., Kristiana, I., et al.[2007]

The review analyzed 100 studies on various therapeutic approaches for interstitial cystitis/bladder pain syndrome (IC/BPS), highlighting that most research focuses on agents recommended by the American Urological Association and those approved for other diseases.

Emerging treatments, including stem cells and plant-derived agents, show promise, but the overall methodological quality of animal studies needs improvement to enhance the translation of findings to clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of Therapeutic Approaches Used in Experimental Models of Interstitial Cystitis/Bladder Pain Syndrome. Kuret, T., Peskar, D., Erman, A., et al.[2021]

In a randomized, double-blind, placebo-controlled trial involving 96 patients with interstitial cystitis/bladder pain syndrome, KRP-116D significantly improved symptoms compared to placebo, with a mean reduction of 5.2 points in the symptom index score versus 3.4 points for placebo.

KRP-116D was well-tolerated, with only mild to moderate adverse reactions, indicating a favorable safety profile for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intravesical instillation of KRP-116D (50% dimethyl sulfoxide solution) for interstitial cystitis/bladder pain syndrome in Japanese patients: A multicenter, randomized, double-blind, placebo-controlled, clinical study. Yoshimura, N., Homma, Y., Tomoe, H., et al.[2021]

In a study involving 39 spinal cord injured adults, both capsaicin (CAP) and resiniferatoxin (RTX) showed similar efficacy in improving detrusor hyperreflexia, with 78% of CAP patients and 80% of RTX patients experiencing clinical improvement after 30 days.

There were no significant differences in side effects between the two treatments, indicating that both CAP and RTX are well-tolerated options for patients with detrusor hyperreflexia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical capsaicin versus resiniferatoxin for the treatment of detrusor hyperreflexia in spinal cord injured patients: a double-blind, randomized, controlled study. de Sèze, M., Wiart, L., de Sèze, MP., et al.[2013]

The vanilloid receptor type 1 (VR-1) is found in sensory neurons of the urinary bladder, and its activation by substances like capsaicin or resiniferatoxin (RTX) can lead to a temporary desensitization of these neurons, reducing their reactivity to stimuli.

Intravesical administration of capsaicin or RTX has shown potential therapeutic benefits for patients with bladder conditions, such as detrusor hyperreflexia and idiopathic detrusor instability, by targeting the abundant VR-1 fibers in the bladder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vanilloid receptor and detrusor instability. Cruz, F.[2019]

The study found that prolonged stimulation of alpha 1A adrenoceptors with phenylephrine (PHE) induces chronic visceral pain (CVP) in female Wistar rats, which can be reversed by silodosin, indicating a potential therapeutic target for managing CVP.

The mechanism appears to involve the interaction between alpha 1A adrenoceptors and TRPV1 nociceptors, as TRPV1 knockout mice did not exhibit pain from PHE, and PHE also enhanced ATP release from human urothelial cells, suggesting a role in bladder hyperactivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bladder pain induced by prolonged peripheral alpha 1A adrenoceptor stimulation involves the enhancement of transient receptor potential vanilloid 1 activity and an increase of urothelial adenosine triphosphate release. Matos, R., Cordeiro, JM., Coelho, A., et al.[2018]

Intravesical administration of resiniferatoxin (RTX) during spinal shock in rats significantly improved bladder function, reducing pressures and contraction amplitudes, indicating its efficacy in modulating bladder activity.

RTX works by desensitizing TRPV1-expressing bladder afferents, suggesting that early treatment could prevent the development of neurogenic detrusor overactivity (NDO) and improve the quality of life for patients with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of early intravesical administration of resiniferatoxin to spinal cord-injured rats in neurogenic detrusor overactivity. Oliveira, R., Coelho, A., Franquinho, F., et al.[2020]

In a study using TRPV1 knock-out and wild-type mice, it was found that TRPV1 is crucial for the development of bladder mechanical hyperreactivity associated with cystitis, indicating its role in visceral pain.

While TRPV1 is important for the sensation of pain related to bladder inflammation, it does not affect the overall inflammatory response or sensitivity to thermal stimuli, suggesting that other pathways may be involved in these processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of TRPV1 inhibits cystitis-induced increased mechanical sensitivity in mice. Wang, ZY., Wang, P., Merriam, FV., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Use of vanilloids in urologic disorders. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

The molecular basis of urgency: regional difference of vanilloid receptor expression in the human urinary bladder. [2007]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A Systematic Review of Therapeutic Approaches Used in Experimental Models of Interstitial Cystitis/Bladder Pain Syndrome. [2021]

4. Australia pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intravesical instillation of KRP-116D (50% dimethyl sulfoxide solution) for interstitial cystitis/bladder pain syndrome in Japanese patients: A multicenter, randomized, double-blind, placebo-controlled, clinical study. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Intravesical capsaicin versus resiniferatoxin for the treatment of detrusor hyperreflexia in spinal cord injured patients: a double-blind, randomized, controlled study. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Vanilloid receptor and detrusor instability. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Bladder pain induced by prolonged peripheral alpha 1A adrenoceptor stimulation involves the enhancement of transient receptor potential vanilloid 1 activity and an increase of urothelial adenosine triphosphate release. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Effects of early intravesical administration of resiniferatoxin to spinal cord-injured rats in neurogenic detrusor overactivity. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Lack of TRPV1 inhibits cystitis-induced increased mechanical sensitivity in mice. [2021]