A Phase 1 Dose Escalation Study to Evaluate Safety and Pharmacokinetics (PK) of VX-840 in Healthy Participants

Overseen By Medical Information

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Vertex Pharmaceuticals Incorporated

Disqualifiers: Febrile illness, Acute illness, others

Compensation: Varies

Number of Visits: Unknown

88 Participants Needed

Trial Summary

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.

What safety data exists for VX-840 or similar treatments?

In a study of VX-128, a similar treatment, single doses were generally well-tolerated, but multiple doses led to skin rashes and a serious allergic reaction in one person. This suggests potential safety concerns with repeated use. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial tests a new drug called VX-840 to see if it is safe and well-tolerated in healthy people. The study focuses on safety before using the drug in patients who might need it.

Eligibility Criteria

Inclusion Criteria

Body mass index (BMI) of 18.0 to 32.0 kilograms per meter square (kg/m^2)

A total body weight greater than (>) 50 kg

Female participants must be of non-childbearing potential

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive a single dose of VX-840 or placebo at different dose levels

1 week

Treatment Part B

Participants receive multiple doses of VX-840 or placebo at different dose levels, determined based on Part A data

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• VX-840

Participant Groups

Group I: Part B: VX-840 Experimental Treatment 1 Intervention

Participants will be randomized to receive multiple doses of one of different dose levels of VX-840. The dose levels will be determined based on the data from Part A.

Group II: Part A: VX-840 Experimental Treatment 1 Intervention

Participants will be randomized to receive single dose of one of different dose levels of VX-840.

Group III: Part A: Placebo Placebo Group 1 Intervention

Participants will receive placebo matched to VX-840.

Group IV: Part B: Placebo Placebo Group 1 Intervention

Participants will receive placebo matched to VX-840.

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

Findings from Research

VX-787 is a promising new oral medication for treating both pandemic and seasonal influenza, showing strong potential in its class.

Research on carboxylic acid isosteres of VX-787 revealed that maintaining a negative charge is crucial for the drug's effectiveness and selectivity against influenza A, as neutral replacements significantly reduced potency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isosteric replacements of the carboxylic acid of drug candidate VX-787: Effect of charge on antiviral potency and kinase activity of azaindole-based influenza PB2 inhibitors. Boyd, MJ., Bandarage, UK., Bennett, H., et al.[2019]

VX-128, a selective Nav 1.8 inhibitor, was found to be well-tolerated in single doses up to 300 mg, but showed a higher incidence of adverse effects compared to placebo, with 41.7% of subjects experiencing side effects.

In a multiple-ascending dose study, skin rashes and one serious case of angioedema were reported, leading to early termination of the study, although VX-128 demonstrated a dose-dependent trend in increasing pain tolerance in certain pain tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I, randomized, double-blind, placebo-controlled, single- and multiple dose escalation study evaluating the safety, pharmacokinetics and pharmacodynamics of VX-128, a highly selective Nav 1.8 inhibitor, in healthy adults. Hijma, HJ., van Brummelen, EMJ., Siebenga, PS., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Isosteric replacements of the carboxylic acid of drug candidate VX-787: Effect of charge on antiviral potency and kinase activity of azaindole-based influenza PB2 inhibitors. [2019]

2. England pubmed.ncbi.nlm.nih.gov

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Pharmacodynamic Effects of VX-150, a Highly Selective NaV1.8 Inhibitor, in Healthy Male Adults. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Humidity induced phase transformation of poloxamer 188 and its effect on physical stability of amorphous solid dispersion of AMG 579, a PDE10A inhibitor. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Clinical safety and hypothalamic-pituitary-adrenal axis effects of the arginine vasopressin type 1B receptor antagonist ABT-436. [2021]

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

A phase I, randomized, double-blind, placebo-controlled, single- and multiple dose escalation study evaluating the safety, pharmacokinetics and pharmacodynamics of VX-128, a highly selective Nav 1.8 inhibitor, in healthy adults. [2022]