VX-121 Combination Therapy for Cystic Fibrosis

No longer recruiting at 151 trial locations

Overseen By Medical Information

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Vertex Pharmaceuticals Incorporated

Disqualifiers: Transplant history, Hepatic impairment, Lung infection, 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

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of medications to evaluate their effectiveness and safety for individuals with cystic fibrosis who have a specific genetic profile. The trial compares two treatments: the experimental VX-121/TEZ/D-IVA and the already-approved ELX/TEZ/IVA (also known as Trikafta or Kaftrio). It seeks participants with cystic fibrosis who have the F508del genetic mutation and another minimal function mutation. Those with this genetic setup and breathing issues related to the condition may find this trial suitable. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that the VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) treatment has been tested for safety in people with cystic fibrosis (CF). Previous studies indicate that this combination is generally well-tolerated, with participants not experiencing unexpected or severe side effects.

For the ELX/tezacaftor/ivacaftor (ELX/TEZ/IVA) treatment, research indicates it is safe and effective. Studies found that people using ELX/TEZ/IVA had fewer lung problems and required fewer hospital visits compared to those not using the treatment. This suggests it is safe for long-term use and helps improve lung health.

Both treatment combinations remain under study, but current evidence suggests they are safe for people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about VX-121 combination therapy for cystic fibrosis because it offers a potentially more effective treatment option by incorporating a new active ingredient, VX-121. Unlike the standard of care, which typically involves combinations like ELX/TEZ/IVA, this treatment includes VX-121 alongside TEZ and D-IVA, which may enhance efficacy. VX-121 targets the underlying defect in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, aiming to improve lung function and reduce symptoms more significantly than current therapies. By offering a new mechanism of action and the potential for improved patient outcomes, VX-121 combination therapy could represent a significant advancement in cystic fibrosis care.

What evidence suggests that this trial's treatments could be effective for cystic fibrosis?

Studies have shown that the treatment ELX/TEZ/IVA, which participants in this trial may receive, significantly improves health outcomes for people with cystic fibrosis (CF). Those using this treatment have experienced better lung function and fewer symptoms over time. Research also confirms that this treatment is generally safe and provides long-lasting benefits.

For VX-121/TEZ/D-IVA, another treatment option in this trial, early findings suggest it helps the CFTR protein function more effectively. This protein plays a crucial role in managing CF symptoms, so improvements here could lead to better lung health and fewer complications. While more data is still being collected, this treatment's mechanism shows promise for enhancing health in CF patients. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Your lung function, measured by FEV1, should be between 40% and 80% if you are not currently taking ELX/TEZ/IVA.

Your lung function, measured by FEV1, should be between 40% and 90% of the expected value based on your age, sex, and height if you are taking ELX/TEZ/IVA therapy.

You have a specific combination of genetic mutations called F508del and minimal function mutation.

Exclusion Criteria

You have a lung infection caused by certain germs that can make your breathing get worse quickly.

Pregnant or breast-feeding females

You have severe liver problems or high blood pressure in the liver.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Participants undergo a run-in period with ELX/TEZ/IVA for 4 weeks

4 weeks

Treatment

Participants receive VX-121/TEZ/D-IVA or ELX/TEZ/IVA for 52 weeks

52 weeks

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
• Placebo (matched to ELX/TEZ/IVA)
• Placebo (matched to IVA)
• Placebo (matched to VX-121/TEZ/D-IVA)
• VX-121/TEZ/D-IVA

Trial Overview 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.

How Is the Trial Designed?

Group I: VX-121/TEZ/D-IVA Experimental Treatment 3 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/IVA Active Control 3 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.

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

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40379539/

LONGITUDE: An observational study of the long-term ... People with CF aged ≥12 years in the UK who initiated ELX/TEZ/IVA had sustained improvements in multiple CF-related health outcomes, consistent with results ...

2. 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 ... ALYFTREK has shown greater reductions in sweat chloride compared to TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) in Phase 3 trials ...

3. jmcp.org jmcp.org/doi/10.18553/jmcp.2023.29.6.599

Real-world outcomes and direct care cost before and after ... Average member total cost of care was 3 times higher in the first 6 months following ELX/TEZ/IVA therapy start compared with the previous 6 months.

4. 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.

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

Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/ ... These results confirm the favorable long-term safety profile and durable disease-modifying clinical benefits of ELX/TEZ/IVA in adolescents and adults with CF.

6. sciencedirect.com sciencedirect.com/science/article/pii/S1569199323000668

Real-world safety and effectiveness of elexacaftor ... ELX/TEZ/IVA treatment was associated with sustained improvements in lung function, reduced frequency of PEx and all-cause hospitalization, increased BMI, and ...

7. atsjournals.org atsjournals.org/doi/abs/10.1164/rccm.202502-0512OC

A 192-Week, Phase 3, Open-Label Extension Study Rationale: Elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) was shown to be safe and efficacious in children 6 through 11 years of age ...

8. 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.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT05111145

A Study Evaluating the Safety of Elexacaftor/Tezacaftor ... The purpose of this study is to evaluate the safety and tolerability of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) in participants with CF who are 12 ...