What side effects are associated with this type of intervention?

CFTR modulators, such as Vanzacaftor/Tezacaftor/Deutivacaftor, are commonly used to improve CFTR protein function in Cystic Fibrosis patients. Known side effects of these treatments include respiratory symptoms (chest tightness, shortness of breath), gastrointestinal issues (nausea, diarrhea, abdominal pain), elevated liver enzymes, headaches, dizziness, and rashes. The severity and frequency of these side effects can vary among individuals.

What prior FDA approvals exist?

The FDA has approved several CFTR modulators for the treatment of Cystic Fibrosis, which aim to improve the function of the defective CFTR protein. Key drugs include Ivacaftor (Kalydeco), which was the first CFTR modulator approved in 2012 for patients with specific CFTR mutations. Lumacaftor/Ivacaftor (Orkambi) was approved in 2015 for patients with two copies of the F508del mutation. Tezacaftor/Ivacaftor (Symdeko) received approval in 2018 for patients with at least one F508del mutation or other responsive mutations. More recently, Elexacaftor/Tezacaftor/Ivacaftor (Trikafta) was approved in 2019 for patients with at least one F508del mutation, significantly expanding treatment options. These drugs work by enhancing the function of the CFTR protein, thereby improving lung function and other symptoms in CF patients.

What other types of research exist?

Promising novel alternatives to Vanzacaftor/Tezacaftor/Deutivacaftor for cystic fibrosis patients include: 1. VX-121/Tezacaftor/VX-561: A new triple combination therapy showing improved efficacy in clinical trials. 2. Elexacaftor/Tezacaftor/Ivacaftor: Another triple combination therapy that has been effective in patients with various CFTR mutations. 3. Gene therapy approaches: Ongoing research into gene editing techniques like CRISPR/Cas9 to correct CFTR mutations at the DNA level. 4. Anti-infective agents: Inhaled antibiotics like aztreonam lysine and tobramycin for managing chronic Pseudomonas aeruginosa infections. 5. Anti-inflammatory therapies: Drugs targeting inflammation pathways to reduce lung damage and improve pulmonary function.

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CFTR Modulator

Triple Combination Therapy for Cystic Fibrosis

Q: What is the mechanism of action of this treatment?

CFTR modulators, such as ivacaftor (a potentiator) and lumacaftor, tezacaftor, and elexacaftor (correctors), work by enhancing the function and proper folding of the CFTR protein, which is defective in Cystic Fibrosis patients. Potentiators improve the activity of the CFTR protein at the cell surface, while correctors assist in the proper folding and trafficking of the protein to the cell surface. These treatments are vital as they address the root cause of CF, leading to improved lung function, reduced symptoms, and overall better health outcomes for patients.

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

Must not have

History of solid organ, hematological transplantation, or cancer

Hepatic cirrhosis with portal hypertension, moderate hepatic impairment, or severe hepatic impairment that might pose an additional risk in administering study drug

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial is testing a combination of three medications to help people with cystic fibrosis. The goal is to see if these drugs are safe and effective over time. These medications work by improving the function of a faulty protein in cystic fibrosis patients, which can enhance their lung function and overall health. Trikafta is a combination of three drugs (elexacaftor, tezacaftor, and ivacaftor) that target the F508del mutation of the CFTR gene.

Who is the study for?

This trial is for people with cystic fibrosis who finished treatment in a previous study (VX21-121-105). It's not open to those who've had organ transplants, cancer, drug intolerance during the prior study, or serious liver issues like cirrhosis with portal hypertension.

What is being tested?

The trial tests the long-term safety and effectiveness of a combination medication called vanzacaftor/tezacaftor/deutivacaftor (VNZ/TEZ/D-IVA) for individuals with cystic fibrosis.

What are the potential side effects?

While specific side effects are not listed here, common ones associated with CF treatments may include chest discomfort, coughing, digestive changes, and potential liver problems. The exact side effects will be monitored throughout the trial.

Eligibility Criteria

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of organ transplant or cancer.

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I have severe liver problems that could make taking new medications risky.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

Pivotal Trial

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

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: VNZ/TEZ/D-IVAExperimental Treatment1 Intervention

Participants (Cohort 1: 6 through 11 years of age (inclusive); Cohort 2: 2 through 5 years of age (inclusive) and Cohort 3: 1 to less than (\<) 2 years of age) will receive VNZ/TEZ/D-IVA once daily at doses determined based on their age and weight. The age range is based on date of informed consent in parent study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

VNZ/TEZ/D-IVA

2024

Completed Phase 1

~50

0 / 2Eligibility criteria met

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 ivacaftor (a potentiator) and lumacaftor, tezacaftor, and elexacaftor (correctors), work by enhancing the function and proper folding of the CFTR protein, which is defective in Cystic Fibrosis patients. Potentiators improve the activity of the CFTR protein at the cell surface, while correctors assist in the proper folding and trafficking of the protein to the cell surface. These treatments are vital as they address the root cause of CF, leading to improved lung function, reduced symptoms, and overall better health outcomes for patients.

Small-molecule drugs for cystic fibrosis: Where are we now?Net benefit of ivacaftor during prolonged tezacaftor/elexacaftor exposure in vitro.Modulators of CFTR. Updates on clinical development and future directions.