ELX/TEZ/IVA for Cystic Fibrosis

Not currently recruiting at 22 trial locations

Overseen By Medical Information

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Vertex Pharmaceuticals Incorporated

Must be taking: Elexacaftor, Tezacaftor, Ivacaftor

Disqualifiers: Drug intolerance, Poor compliance, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a treatment for cystic fibrosis, a condition affecting breathing and digestion. The goal is to assess the long-term safety and effectiveness of a medication combination: elexacaftor (ELX), tezacaftor (TEZ), and ivacaftor (IVA). Participants will take ELX/TEZ/IVA in the morning and IVA in the evening. Those who completed a related study with these drugs without issues may be suitable candidates for this trial. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Trikafta (ELX/TEZ/IVA) has been tested in over 500 people with cystic fibrosis. Participants were at least 12 years old and had a specific gene mutation. The studies, which lasted 24 weeks, found that the treatment is generally well-tolerated. However, some serious side effects, including liver damage and, in rare cases, liver failure, were reported.

Trikafta is already approved for treating cystic fibrosis in people over 12, suggesting it is considered safe for older children and adults. However, its safety for children under 2 years old remains unknown. Those considering joining a trial should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cystic fibrosis?

ELX/TEZ/IVA is unique because it targets the root cause of cystic fibrosis by addressing the malfunctioning CFTR protein. Unlike older treatments that only manage symptoms, this combination therapy works at a molecular level to improve protein function and enhance chloride transport across cell membranes. Researchers are excited because this approach has the potential to significantly improve lung function and overall quality of life for patients with cystic fibrosis.

What evidence suggests that ELX/TEZ/IVA is effective for cystic fibrosis?

Research has shown that the combination of elexacaftor, tezacaftor, and ivacaftor (ELX/TEZ/IVA) holds promise for treating cystic fibrosis. Studies have found significant improvements in lung function and reductions in sweat chloride levels, both key indicators of the disease. Participants taking this treatment experienced 63% fewer lung flare-ups compared to those on a placebo. Real-world data also indicates fewer hospital and emergency room visits for those on this medication. Overall, these findings suggest that ELX/TEZ/IVA effectively manages cystic fibrosis symptoms. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for people aged 2 and older with cystic fibrosis who have previously participated in a related study (VX20-445-111 Part B) without permanently stopping the study drug. Those with a history of not following treatment or procedures well, or intolerance to the study drug in the previous research, cannot join.

Inclusion Criteria

Completed study drug treatment in the parent study (VX20-445-111 Part B, NCT04537793), or had study drug interruption(s) in the parent study, but did not permanently discontinue study drug, and completed study visits up to the last scheduled visit of the Treatment Period of the parent study

Exclusion Criteria

I have had issues following treatment or study rules in the past.

You had a bad reaction to the study drug in a previous study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ELX/TEZ/IVA in the morning and IVA in the evening to evaluate long-term safety and efficacy

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ELX/TEZ/IVA
• IVA

Trial Overview The trial is looking at long-term safety and effectiveness of a combination medication (elexacaftor/tezacaftor/ivacaftor) for cystic fibrosis. It will assess how well patients tolerate this treatment over time and its impact on their condition.

How Is the Trial Designed?

Group I: ELX/TEZ/IVA Experimental Treatment 2 Interventions

Participants will receive ELX/TEZ/IVA in the morning and IVA in the evening.

ELX/TEZ/IVA is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Trikafta for:

• Cystic fibrosis in patients aged 2 years and older with at least one copy of the F508del mutation in the CFTR gene or another mutation responsive to treatment

Approved in European Union as Kaftrio for:

• Cystic fibrosis in patients aged 2 years and older with at least one copy of the F508del mutation in the CFTR gene or another mutation responsive to treatment

Approved in Canada as Trikafta for:

• Cystic fibrosis in patients aged 2 years and older with at least one copy of the F508del mutation in the CFTR gene or another mutation responsive to treatment

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

In a study of 19 cystic fibrosis patients treated with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) for 6 months, significant improvements were observed in lung structure, including reduced bronchial wall thickening and mucus plugging, as assessed by MRI.

Patients also showed marked clinical benefits, including improved respiratory function (FEV1% increased from 58.5% to 71.4%), better body mass index, and reduced pulmonary exacerbations, confirming the efficacy of ELX/TEZ/IVA in managing cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structural changes in lung morphology detected by MRI after modulating therapy with elexacaftor/tezacaftor/ivacaftor in adolescent and adult patients with cystic fibrosis. Fainardi, V., Skenderaj, K., Ciuni, A., et al.[2023]

In a study of 16 cystic fibrosis patients treated with the combination therapy of elexacaftor, tezacaftor, and ivacaftor (ELX-TEZ-IVA), 37.5% developed new acneiform rashes, while 62.5% experienced a relapse or worsening of previous acne, indicating a notable skin-related side effect of this treatment.

Despite the occurrence of acneiform eruptions, most cases were mild and manageable with treatments like topical medications and isotretinoin, leading to partial or complete remission in 85.7% of patients reevaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acneiform Eruption Following Elexacaftor-Tezacaftor-Ivacaftor Treatment in Patients With Cystic Fibrosis. Okroglic, L., Sohier, P., Martin, C., et al.[2023]

In a study of 16,116 cystic fibrosis patients treated with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) for an average of 20.4 months, there was a significant 79% reduction in pulmonary exacerbations and a 74% reduction in hospitalizations compared to the 5-year pre-treatment period.

The treatment also led to sustained improvements in lung function (average increase of 8.9 percentage points in forced expiratory volume in 1 second by Year 2), increased body mass index, and a notable decrease in the rates of death (72% lower) and lung transplantation (85% lower) compared to the year before the treatment became available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world safety and effectiveness of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis: Interim results of a long-term registry-based study. Bower, JK., Volkova, N., Ahluwalia, N., et al.[2023]

In a study involving eight cystic fibrosis patients with the N1303K mutation, treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) led to significant improvements in lung function, with an average increase of 18.4 percentage points in forced expiratory volume after 8 weeks.

The treatment also resulted in a notable increase in body mass index (BMI) and improvements in CFTR channel activity in intestinal organoids, indicating that ELX/TEZ/IVA can provide clinical benefits for patients with the N1303K mutation, despite it not being included in the original list of responsive mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and functional efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis carrying the N1303K mutation. Sadras, I., Kerem, E., Livnat, G., et al.[2023]

In a study of 13 lung transplant recipients (LTRs) using elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), the therapy was found to be poorly tolerated, with 38.4% of patients discontinuing due to issues like declining pulmonary function and mood disturbances.

Despite the challenges, 46.2% of patients reported improvements in sinus symptoms and a significant reduction in tacrolimus dose requirements (by 50%), indicating some therapeutic benefit for extrapulmonary cystic fibrosis manifestations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poor tolerability of cystic fibrosis transmembrane conductance regulator modulator therapy in lung transplant recipients. Doligalski, CT., McKinzie, CJ., Yang, A., et al.[2022]

Citations

1. news.vrtx.com news.vrtx.com/news-releases/news-release-details/vertex-presents-new-data-across-portfolio-cystic-fibrosis

Vertex Presents New Data Across Portfolio of Cystic Fibrosis ... “Real-world outcomes in people with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) with up to four years of follow- ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1569199325014675

LONGITUDE: An observational study of the long-term ... LONGITUDE is an observational, registry-based cohort study using data from the UK CF Registry to evaluate outcomes of ELX/TEZ/IVA in people aged ≥6 years.

3. trikafta.com trikafta.com/study-information

Studies and Results | TRIKAFTA® (elexacaftor/tezacaftor ... Through 24 weeks, the number of pulmonary exacerbations significantly decreased by 63% for people taking TRIKAFTA compared with placebo.

4. jmcp.org jmcp.org/doi/10.18553/jmcp.2023.29.6.599

Real-world outcomes and direct care cost before and after ... Among 494 commercially insured members diagnosed with cystic fibrosis, a meaningful decrease in hospitalizations, emergency department visits, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12365565/

Efficacy of Trikafta (ELX/TEZ/IVA) & Symdeko (TEZ/IVA) in ... Its efficacy, as demonstrated by significant improvements in FEV1 levels, reduction in sweat chloride levels, and enhanced Cystic Fibrosis Questionnaire-Revised ...

6. trikaftahcp.com trikaftahcp.com/safety-profile

Safety Profile | TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor ... Safety data from 510 patients aged 12 years and older with CF with at least one F508del mutation in 2 double‑blind, controlled, Phase 3 trials of 24 weeks ...

7. trikafta.com trikafta.com/

TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) TRIKAFTA is a prescription medicine used for the treatment of cystic fibrosis ... It is not known if TRIKAFTA is safe and effective in children under 2 years of ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40209082/

Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/ ... Rationale: Clinical and real-world studies show that elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is efficacious and safe in people with cystic fibrosis ...

9. trikafta.com trikafta.com/important-safety-information

Important Safety Information TRIKAFTA can cause serious liver damage and liver failure. Liver failure leading to transplantation and death has been seen in some people with or without a ...

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/212273s004lbl.pdf

TRIKAFTA® (elexacaftor, tezacaftor, and ivacaftor tablets The safety profile of TRIKAFTA is based on data from 510 CF patients aged 12 years and older in two double-blind, controlled trials of 24 weeks and 4 weeks.