What is the mechanism of action of this treatment?

CFTR modulators, such as VX-121/tezacaftor/deutivacaftor, work by correcting the malfunctioning CFTR protein in Cystic Fibrosis patients, thereby improving chloride ion transport across cell membranes. This helps to reduce the thick, sticky mucus that clogs the airways, leading to better lung function and fewer pulmonary exacerbations. This mechanism is vital for CF patients as it directly addresses the underlying cause of the disease, improving respiratory health and overall quality of life. Other treatments, including antibiotics, mucolytics, and airway clearance techniques, manage symptoms and prevent complications, further supporting patient health.

What side effects are associated with this type of intervention?

Common treatments for Cystic Fibrosis, particularly CFTR modulators like VX-121/tezacaftor/deutivacaftor, include drugs such as ivacaftor, lumacaftor, tezacaftor, and elexacaftor. Known side effects of these treatments can include respiratory symptoms (e.g., chest tightness, shortness of breath), gastrointestinal issues (e.g., nausea, diarrhea), liver enzyme elevations, and rash. Patients may also experience headaches and dizziness. It is important to monitor for these side effects and discuss any concerns with a healthcare provider.

What prior FDA approvals exist?

The FDA has approved several CFTR modulators for the treatment of Cystic Fibrosis, targeting the defective CFTR protein. These include ivacaftor (Kalydeco), lumacaftor/ivacaftor (Orkambi), tezacaftor/ivacaftor (Symdeko), and elexacaftor/tezacaftor/ivacaftor (Trikafta). These drugs have shown efficacy in improving lung function and reducing pulmonary exacerbations in CF patients with specific CFTR mutations. The ongoing study of VX-121/tezacaftor/deutivacaftor aims to further enhance treatment options for CF patients, particularly those heterozygous for F508del and a minimal function mutation.

What other types of research exist?

Promising alternatives to VX-121/tezacaftor/deutivacaftor for cystic fibrosis patients include the triple-combination therapy elexacaftor/tezacaftor/ivacaftor (Trikafta), which has shown significant clinical benefits in patients with the F508del mutation. Additionally, ongoing research into gene editing and mRNA therapies, such as those targeting the CFTR gene directly, may offer novel treatment options in the near future.

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CFTR Modulator

VX-121 Combination Therapy for Cystic Fibrosis

Phase 3

Waitlist Available

Research Sponsored by Vertex Pharmaceuticals Incorporated

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from baseline through week 24

Awards & highlights

Pivotal Trial

Summary

This trial tests a combination of three drugs to help cystic fibrosis patients with a specific genetic mutation. The drugs aim to fix a faulty protein in their lungs, improving their ability to breathe. Trikafta is a combination of three drugs that target the F508del mutation in the CFTR gene.

Who is the study for?

This trial is for people with cystic fibrosis who have one F508del mutation and another mutation that minimally functions. They should be able to breathe out at least 40% of the air in their lungs in one second, but not more than 80-90%, depending on current treatments. People with severe liver problems, certain lung infections, or those pregnant or breastfeeding cannot join.

What is being tested?

The study tests VX-121/TEZ/D-IVA's effectiveness and safety against cystic fibrosis compared to a placebo and other therapies like ELX/TEZ/IVA. Participants will randomly receive either the test drug combination or a matching placebo.

What are the potential side effects?

While specific side effects are not listed here, participants may experience issues related to the digestive system, liver function changes, potential allergic reactions, respiratory symptoms worsening temporarily after treatment initiation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from baseline through week 24

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from baseline through week 24

This trial's timeline: 3 weeks for screening, Varies for treatment, and from baseline through week 24 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

Secondary study objectives

Absolute Change in Sweat Chloride (SwCl)

Percentage of Participants With SwCl <30 mmol/L (Pooled With Data From Study VX20-121-103)

Percentage of Participants With SwCl <60 mmol/L (Pooled With Data From Study VX20-121-103)

Side effects data

From 2023 Phase 3 trial • 435 Patients • NCT05033080

32%

Infective pulmonary exacerbation of cystic fibrosis

26%

COVID-19

20%

Cough

17%

Nasopharyngitis

13%

Upper respiratory tract infection

12%

Nasal congestion

11%

Oropharyngeal pain

11%

Blood creatine phosphokinase increased

11%

Headache

10%

Pyrexia

10%

Sputum increased

Viral upper respiratory tract infection

Back pain

Nausea

Fatigue

Rhinorrhoea

Diarrhoea

Abdominal pain

Respiratory tract infection

Arthralgia

Abdominal distension

Haemoptysis

Influenza

Alanine aminotransferase increased

Sinusitis

Aspartate aminotransferase increased

Rash

Abdominal pain upper

Sinus congestion

Productive cough

Constipation

100%

80%

60%

40%

20%

Study treatment Arm

ELX/TEZ/IVA

VNZ/TEZ/D-IVA

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: VX-121/TEZ/D-IVAExperimental Treatment3 Interventions

Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.

Group II: ELX/TEZ/IVAActive Control3 Interventions

Following elexacftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) run-in period of 4 weeks, participants received ELX 200 milligram (mg) once daily (qd) /TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the treatment period for 52 weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

VX-121/TEZ/D-IVA

2022

Completed Phase 3

~1070

Placebo (matched to ELX/TEZ/IVA)

2020

Completed Phase 3

~1460

Placebo (matched to IVA)

2020

Completed Phase 3

~1580

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

CFTR modulators, such as VX-121/tezacaftor/deutivacaftor, work by correcting the malfunctioning CFTR protein in Cystic Fibrosis patients, thereby improving chloride ion transport across cell membranes. This helps to reduce the thick, sticky mucus that clogs the airways, leading to better lung function and fewer pulmonary exacerbations. This mechanism is vital for CF patients as it directly addresses the underlying cause of the disease, improving respiratory health and overall quality of life. Other treatments, including antibiotics, mucolytics, and airway clearance techniques, manage symptoms and prevent complications, further supporting patient health.