What side effects are associated with this type of intervention?

Common treatments for Cystic Fibrosis, particularly CFTR modulators like ivacaftor, lumacaftor, tezacaftor, and elexacaftor, can have side effects such as liver enzyme elevations, respiratory symptoms (e.g., chest tightness, shortness of breath), gastrointestinal disturbances (e.g., nausea, diarrhea), and rash. Antibiotic treatments, often used to manage chronic infections, can lead to side effects like nephrotoxicity, ototoxicity, and gastrointestinal upset. Inhaled antibiotics may cause bronchial constriction and throat irritation. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several CFTR modulators for the treatment of Cystic Fibrosis, targeting the underlying genetic defect in the CFTR gene. Notable approvals include ivacaftor (Kalydeco), which was the first CFTR modulator approved for patients with specific CFTR mutations. This was followed by the approval of lumacaftor/ivacaftor (Orkambi) and tezacaftor/ivacaftor (Symdeko), which are used for patients with two copies of the F508del mutation. More recently, the triple combination therapy elexacaftor/tezacaftor/ivacaftor (Trikafta) was approved, significantly expanding treatment options for patients with at least one F508del mutation. These treatments have shown to improve lung function and reduce pulmonary exacerbations in CF patients.

What other types of research exist?

Promising novel alternatives to VX-121/tezacaftor/deutivacaftor for cystic fibrosis patients include elexacaftor/tezacaftor/ivacaftor (Trikafta), which has shown significant improvements in lung function and quality of life. Additionally, ongoing research into gene therapy and mRNA-based treatments offers potential future alternatives by targeting the underlying genetic cause of CF.

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CFTR Modulator

VX-121 + Tezacaftor + Deutivacaftor for Cystic Fibrosis

Phase 3

Recruiting

Research Sponsored by Vertex Pharmaceuticals Incorporated

Eligibility Criteria Checklist

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

Must have

Participants with stable CF and at least 1 TCR mutation (including F508del) in the CFTR gene

Be younger than 18 years old

Must not have

Moderate hepatic impairment (Child Pugh Score 7 to 9)

History of solid organ, hematological transplantation, or cancer

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial tests a combination of three drugs for cystic fibrosis patients with a specific genetic mutation. The drugs work together to fix the faulty protein in their cells, helping their lungs and other organs function better. Trikafta is a combination of three drugs (elexacaftor, tezacaftor, and ivacaftor) that target the F508del mutation in the CFTR gene.

Who is the study for?

This trial is for children aged 1-11 with stable cystic fibrosis who have at least one mutation responsive to the treatment. It's not suitable for those with a history of organ transplant, cancer, significant liver disease, or certain lung infections that worsen breathing.

What is being tested?

The study tests VX-121/tezacaftor/deutivacaftor in young CF patients to see how their bodies handle it and if it's safe and effective. The medication aims to improve lung function by targeting the defective protein causing CF.

What are the potential side effects?

While specific side effects aren't listed here, common ones for CF treatments include chest discomfort, coughing, digestive changes, and potential liver issues. Monitoring during the trial helps manage any adverse reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cystic fibrosis is stable and I have at least one CFTR gene mutation.

Exclusion Criteria

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

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My liver function is moderately impaired.

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I have a history of organ transplant or cancer.

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My liver is severely impaired.

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I have a lung infection that worsens my breathing condition quickly.

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I have liver cirrhosis with increased blood pressure in the liver.

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

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%

Blood creatine phosphokinase increased

11%

Oropharyngeal pain

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

No Placebo-Only Group

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

Pivotal Trial

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Part B: VX-121/TEZ/D-IVAExperimental Treatment1 Intervention

Participants will receive VX-121/TEZ/D-IVA in the morning with the dose(s) to be based on the outcome of Part A.

Group II: Part A: VX-121/TEZ/D-IVAExperimental Treatment1 Intervention

Participants will receive VX-121/TEZ/D-IVA in the morning.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

VX-121/TEZ/D-IVA

2022

Completed Phase 3

~1070

0 / 6Eligibility 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 those being studied in the VX-121/tezacaftor/deutivacaftor trial, target the defective CFTR protein caused by mutations in the CFTR gene, which is the root cause of Cystic Fibrosis. Correctors like tezacaftor help the CFTR protein fold correctly and reach the cell surface, while potentiators like ivacaftor enhance the function of the CFTR protein at the cell surface, improving chloride ion transport. These treatments are crucial for CF patients as they address the underlying cause of the disease, leading to improved lung function, reduced pulmonary exacerbations, and overall better quality of life.