VX-993 for Healthy Adults

Overseen By Medical Information

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Vertex Pharmaceuticals Incorporated

Disqualifiers: Febrile illness, Metabolism issues, others

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, VX-993, to assess its safety and how the body processes it. Researchers will administer either a single dose or multiple doses of VX-993 to healthy participants and compare the results to a placebo group. The goal is to understand how different doses affect individuals and identify any side effects. This trial suits non-smokers or those who quit smoking at least 3 months ago and have a stable body weight of over 50 kg. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial is for healthy adults and excludes those with conditions affecting drug distribution, metabolism, or excretion, it's possible that some medications might need to be paused. Please consult with the trial coordinators for specific guidance.

Is there any evidence suggesting that VX-993 is likely to be safe for humans?

Research has shown that VX-993 is generally safe for people. Studies found that most side effects were mild to moderate, with common ones including nausea, dizziness, headache, and vomiting. Importantly, no serious side effects occurred. VX-993's safety was similar to a placebo, meaning participants experienced similar side effects to those taking a non-active substance, indicating a good safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about VX-993 because it potentially offers a fresh approach to managing conditions that currently rely on more traditional therapies. Unlike existing treatments, VX-993 operates through a novel mechanism of action, which could lead to improved efficacy or fewer side effects. Additionally, the study involves both single and multiple ascending doses, allowing researchers to fine-tune the dosage for optimal results. This innovative approach could provide new insights and options for patients who may not fully benefit from current standard treatments.

What evidence suggests that VX-993 could be effective?

Research has shown that VX-993 may help treat certain conditions. In studies focused on pain from diabetic nerve damage, VX-993 generally proved safe, with most side effects being mild to moderate. No serious side effects emerged. Although it's still early, these results suggest VX-993 might help manage pain, and its safety appears promising. More research is needed to fully understand its potential benefits. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for healthy adults who have a BMI between 18.0 and 32.0, weigh more than 50 kg, and are non-smokers or have quit smoking for at least three months.

Inclusion Criteria

My BMI is between 18.0 and 32.0.

I weigh more than 50 kg.

I have not smoked for at least 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Single Ascending Dose (SAD)

Participants receive a single dose of different dose levels of VX-993 or placebo

1-2 weeks

Multiple Ascending Dose (MAD)

Participants receive multiple doses of different dose levels of VX-993 or placebo

4-6 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 is testing the safety and how the body processes different doses of VX-993, a new drug given through an IV, compared to a placebo in people without any health issues.

How Is the Trial Designed?

Group I: Part B: Multiple Ascending Dose (MAD) Experimental Treatment 1 Intervention

Participants will be randomized to receive multiple doses of different dose levels of VX-993. The dose levels will be determined based on the data from Part A.

Group II: Part A: Single Ascending Dose (SAD) Experimental Treatment 1 Intervention

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

Group III: Placebo Part A Placebo Group 1 Intervention

Participants will be randomized to receive placebo matched to VX-993.

Group IV: Placebo Part B Placebo Group 1 Intervention

Participants will be randomized to receive multiple doses of placebo matched to VX-993.

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

A study of 106 serious adverse drug reactions (ADRs) in older adults revealed that systemic reactions were most common, with antibiotics, allopurinol, and cardiovascular drugs being the primary culprits.

Among the older adults studied, 4% experienced fatal outcomes due to serious ADRs, highlighting the need for improved monitoring and analysis of drug safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious adverse drug reactions in older adults notified to pharmacovigilance. Charfi, R., El Aïdli, S., Zaïem, A., et al.[2019]

In a study of 29,585 endurance runners, pre-race medical screening effectively identified participants at higher risk for adverse events (AEs), with the very high-risk group experiencing significantly more AEs compared to the low-risk group.

The findings suggest that risk stratification can help predict who may face challenges during a race, although further research is needed to determine how screening can reduce these risks in larger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-race screening and stratification predicts adverse events-A 4-year study in 29585 ultra-marathon entrants, SAFER X. Sewry, N., Schwellnus, M., Borjesson, M., et al.[2020]

A study analyzing 4,339 adverse events (AEs) associated with radium-223 from the Eudra-Vigilance database found that the most common AEs were hematological, general, and gastrointestinal disorders, with over 90% classified as serious and 8% fatal.

Older patients (over 85 years) treated with radium-223 showed a higher risk of cardiac, infectious, and metabolic disorders compared to younger patients, indicating the need for careful monitoring in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events related to radium-223 treatment: "real-life" data from the Eudra-Vigilance database. Tema, G., Lombardo, R., Voglino, O., et al.[2021]

Pentraxin 3 (PTX3) is expressed and released by human adipose tissue, particularly in visceral adipose tissue (VAT) from obese individuals, suggesting its role in inflammation and atherosclerosis development.

The expression of VAT-PTX3 is correlated with several cardiometabolic risk factors, including TNFalpha levels and the LDL/HDL cholesterol ratio, indicating that PTX3 may be involved in the mechanisms that contribute to cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of long pentraxin PTX3 in human adipose tissue and its relation with cardiovascular risk factors. Alberti, L., Gilardini, L., Zulian, A., et al.[2013]

In a study involving 687 patients with ADHD (ages 6-50), predictors for relapse after stopping long-term atomoxetine treatment were identified, showing that specific ADHD symptoms like 'difficulty awaiting turn' in adults and 'does not listen' in children were linked to a higher likelihood of relapse.

Quality of life changes after discontinuing atomoxetine were found to moderately correlate with changes in ADHD symptoms in children and mildly in adults, suggesting that symptom management is crucial for maintaining overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of relapse or maintenance of response in pediatric and adult patients with attention-deficit/hyperactivity disorder following discontinuation of long-term treatment with atomoxetine. Thome, J., Dittmann, RW., Greenhill, LL., et al.[2018]

In a study of 354 adults with ADHD, early improvements in symptoms after 2 weeks of viloxazine extended-release treatment were able to predict treatment response at Week 6, with a positive predictive power of 68%.

The predictive model developed from pediatric data successfully generalized to adults, indicating that viloxazine ER is effective across different age groups for treating ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting efficacy of viloxazine extended-release treatment in adults with ADHD using an early change in ADHD symptoms: Machine learning Post Hoc analysis of a phase 3 clinical trial. Faraone, SV., Gomeni, R., Hull, JT., et al.[2023]

A safety analysis of ubrogepant and rimegepant, based on 2010 and 3691 adverse event reports respectively, identified 10 and 25 significant safety signals, indicating potential risks associated with these medications.

The adverse events reported were primarily related to psychiatric, neurological, gastrointestinal, skin, vascular, and infectious issues, highlighting the need for further research to confirm these safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ubrogepant and rimegepant: signal detection using spontaneous reports of adverse events from the Food and Drug Administration Adverse Event Reporting System. Battini, V., Carnovale, C., Clementi, E., et al.[2023]

In a study using genetically modified mice, overexpression of the PTX3 protein was found to accelerate the development of ventilator-induced lung injury (VILI), indicating that higher levels of PTX3 may worsen lung damage during mechanical ventilation.

Conversely, mice lacking PTX3 did not show a difference in the time it took to develop VILI compared to normal mice, suggesting that PTX3 may play a role in enhancing the inflammatory response associated with lung injury rather than being essential for its onset.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pentraxin 3 accelerates lung injury in high tidal volume ventilation in mice. Real, JM., Spilborghs, GM., Morato-Marques, M., et al.[2012]

In a study of 1,747 individuals from a Korean community, higher levels of pentraxin-3 (PTX3) were linked to healthier lipid profiles, including higher HDL cholesterol and lower triglycerides, indicating a potential protective role against heart disease.

Subjects with the highest PTX3 levels had a significantly lower risk of metabolic syndrome and obesity, suggesting that PTX3 may be a beneficial biomarker for cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Plasma Pentraxin-3 Level with Lipid Levels and Cardiovascular Risk Factors in People with No History of Lipid-Lowering Medication: the Dong-gu Study. Lee, R., Ahn, HR., Shin, MH., et al.[2020]

In a study of 327 Japanese adults, higher consumption of sugar-sweetened foods and beverages was linked to significantly lower levels of pentraxin 3 (PTX3), an important anti-inflammatory protein that helps protect the heart.

PTX3 levels were influenced by biological sex and various metabolic factors, with specific associations found in women and older adults, indicating that dietary choices and metabolic health can impact this cardioprotective protein.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sugar-Rich Food Intake Is Negatively Associated with Plasma Pentraxin 3 Levels. Zempo-Miyaki, A., Kumagai, H., Tanahashi, K., et al.[2023]

In a study of 147 adults with ADHD, 70.1% experienced treatment success with Atomoxetine after 6 months, indicating its effectiveness as a standard treatment.

Factors influencing Atomoxetine efficacy included the maximum dose prescribed and the presence of a gambling habit, which may reflect impulsivity, a core symptom of ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of factors associated with the efficacy of atomoxetine in adult attention-deficit/hyperactivity disorder. Nagai, T., Kurihara, T., Koya, H., et al.[2022]

In a study involving 384 adults with ADHD treated with atomoxetine for up to 221 weeks, there was a significant reduction in ADHD symptoms, with a 30.2% decrease in the total symptom score (p < .001).

The treatment was found to be safe and well-tolerated, with adverse events primarily related to expected pharmacological effects, supporting the long-term efficacy and safety of atomoxetine for adult ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term, open-label safety and efficacy of atomoxetine in adults with ADHD: final report of a 4-year study. Adler, LA., Spencer, TJ., Williams, DW., et al.[2022]

In a comprehensive review of 54 phase-I studies involving 1015 healthy volunteers over 10 years, the overall incidence of adverse events was found to be 12.8%, with a higher rate for active drugs (13.7%) compared to placebo (7.9%).

Most adverse events were minor, with only 3% classified as severe, and no deaths or life-threatening events reported, highlighting that while adverse events are common in phase-I trials, they are typically not serious.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. Sibille, M., Deigat, N., Janin, A., et al.[2019]

In a study of 1749 healthy Japanese individuals, plasma levels of pentraxin 3 (PTX3) were found to be significantly lower in men compared to women, indicating a potential gender difference in PTX3 levels.

PTX3 levels were inversely correlated with triglycerides and body mass index (BMI), and were lower in individuals with metabolic syndrome, suggesting that PTX3 could serve as a useful biomarker for assessing coronary risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of physiological plasma pentraxin 3 (PTX3) levels in healthy populations. Yamasaki, K., Kurimura, M., Kasai, T., et al.[2016]

In a 12-week trial involving 445 young adults with ADHD, atomoxetine significantly reduced ADHD symptoms compared to placebo, as measured by multiple scales including the Conners' Adult ADHD Rating Scale.

Atomoxetine also improved quality of life and executive functioning in participants, while its side effects were similar to those seen in previous studies, with nausea and decreased appetite being the most common adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atomoxetine treatment of attention-deficit/hyperactivity disorder in young adults with assessment of functional outcomes: a randomized, double-blind, placebo-controlled clinical trial. Durell, TM., Adler, LA., Williams, DW., et al.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06394167

A Phase 1 Dose Escalation Study of Intravenous VX-993 in ... The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of intravenously administered VX-993 at different doses in healthy ...

2. 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 ... VX-993 was generally safe and well tolerated. Most adverse events (AEs) were mild to moderate, and there were no serious adverse events (SAEs) ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06619860

Evaluation of Efficacy and Safety of VX-993 for Pain ... The purpose of this study is to evaluate the efficacy, safety, and tolerability of VX-993 in participants with pain associated with Diabetic Peripheral ...

4. withpower.com withpower.com/trial/phase-1-pain-4-2024-a09e6

VX-993 for Healthy Adults · Info for Participants In a study, about 40% of adults showed improvement after 6 months of treatment with atomoxetine.

5. trialx.com trialx.com/clinical-trials/listings/292091/a-phase-1-dose-escalation-study-of-intravenous-vx-993-in-healthy-adults/

A Phase 1 Dose Escalation Study of Intravenous VX-993 in ... The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of intravenously administered VX-993 at different ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06619860?utm_source=trialradar

Evaluation of Efficacy and Safety of VX-993 for Pain ... Safety continues to be evaluated, and short-term adverse events are studied. ... Evaluation of Efficacy and Safety of VX-993 for Pain Associated With Diabetic ...

7. 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 ... In the latest data update, VX-993 was considered safe and well tolerated across the doses studied, with a rate of adverse events (AEs) that was ...

8. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-vx-993-and-pregabalin-for-pain-relief-in-patients-with-diabetic-peripheral-neuropathy/

Study on the Effectiveness and Safety of VX-993 and ... This clinical trial tests the effectiveness and safety of VX-993, compared to pregabalin, in managing pain caused by diabetic peripheral ...

9. 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 The safety profile of VX-993 was similar to placebo, with the most common adverse events being nausea, dizziness, headache and vomiting, ...