CLINICAL TRIALS PROFILE FOR IVACAFTOR; IVACAFTOR, TEZACAFTOR

All Clinical Trials for IVACAFTOR; IVACAFTOR, TEZACAFTOR

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT03140527 ↗	Study Assessing the Safety, Tolerability, Pharmacokinetics, Food Effect, and Drug-Drug Interactions of PTI-801 in Healthy Volunteers, and Safety, Tolerability, and Pharmacokinetics of PTI-801 in Subjects With Cystic Fibrosis	Completed	Proteostasis Therapeutics, Inc.	Phase 1	2017-04-10	This trial will consist of two parts: Part 1 and Part 2. Part 1 will enroll adult healthy volunteers (HV) into four treatment groups. The first group will enroll HV into a single ascending dose (SAD) treatment group consisting of three cohorts. The second group will enroll HV into a multiple ascending dose (MAD) treatment group consisting of three cohorts. The third group will enroll HV into a food effect (FE) treatment group consisting of one cohort. The fourth group will enroll HV into a drug-drug interactions (DDI) treatment group consisting of one cohort. Approximately 76 subjects will be enrolled in Part 1. Part 2 Cohorts 1 through 3 will enroll adult subjects with cystic fibrosis (CF) currently on stable ivacaftor/lumacaftor background therapy for a minimum of three months. Part 2 Cohorts 4 and Cohort 5 will enroll adult subjects with CF not currently receiving cystic fibrosis conductance regulator (CFTR) modulator therapy within 30 days prior to Day 1. Part 2 Cohort 6 will enroll adult subjects with cystic fibrosis on stable tezacaftor/ivacaftor background therapy. Approximately 104 subjects will be enrolled in Part 2.
NCT02951195 ↗	A Study Evaluating the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis	Completed	Vertex Pharmaceuticals Incorporated	Phase 2	2016-11-01	This is a Phase 2, randomized, double blind, placebo and active-controlled, parallel group, multicenter study designed to evaluate the safety and tolerability of VX-152 in Triple Combination (TC) with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF), or who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F508del/F508del).
NCT02953314 ↗	A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of VX-661/Ivacaftor in Pediatric Subjects With Cystic Fibrosis (CF)	Completed	Vertex Pharmaceuticals Incorporated	Phase 3	2016-11-01	This is a Phase 3, 2-part (Part A and Part B), open label, multicenter study evaluating the pharmacokinetic (PK), safety, and tolerability of multiple doses of tezacaftor (TEZ) in combination with ivacaftor (IVA) in subjects 6 through 11 years of age with CF who are homozygous or heterozygous for the F508del- CF transmembrane conductance regulator protein (CFTR) mutation.
NCT02951182 ↗	A Study Evaluating the Safety and Efficacy of VX-440 Combination Therapy in Subjects With Cystic Fibrosis	Completed	Vertex Pharmaceuticals Incorporated	Phase 2	2016-10-01	This is a Phase 2, randomized, double-blind, placebo- and active-controlled, parallel group, multicenter study to evaluate the safety, tolerability, and efficacy of VX-440 in dual and triple combination with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F508del/F508del), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF).
NCT02730208 ↗	A Study to Evaluate the Effect of VX-661 in Combination With Ivacaftor on Chest Imaging Endpoints in Subjects With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation	Completed	Vertex Pharmaceuticals Incorporated	Phase 2	2016-09-01	The primary purpose of study is to evaluate the treatment effect of tezacaftor in combination with ivacaftor (TEZ/IVA) on chest imaging endpoints using low-dose computed tomography (LDCT) at Week 72, and to evaluate the safety of TEZ/IVA through Week 72.
NCT02508207 ↗	A Phase 2 Study to Evaluate Effects of VX-661/Ivacaftor on Lung and Extrapulmonary Systems in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation	Completed	Vertex Pharmaceuticals Incorporated	Phase 2	2016-02-01	To evaluate the clinical mechanisms of action in lung and extrapulmonary systems of VX-661 (tezacaftor; TEZ) in combination with ivacaftor (IVA) (TEZ/IVA) in participants with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene.
NCT02412111 ↗	A Phase 3 Study of Tezacaftor (VX-661) in Combination With Ivacaftor (VX-770) in Subjects Aged 12 Years and Older With Cystic Fibrosis (CF), Who Have One F508del-CFTR Mutation and a Second Mutation That Has Been Demonstrated to be Clinically Respons	Completed	Vertex Pharmaceuticals Incorporated	Phase 3	2015-06-01	This is a Phase 3, randomized, double-blind, ivacaftor-controlled, parallel-group, multicenter study of tezacaftor in combination with ivacaftor in subjects aged 12 years and older with CF who are heterozygous for the F508del-CFTR mutation and a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive.

Clinical Trial Conditions for IVACAFTOR; IVACAFTOR, TEZACAFTOR

Condition Name

Condition Name for IVACAFTOR; IVACAFTOR, TEZACAFTOR
Intervention	Trials
Cystic Fibrosis	42
Cystic Fibrosis Liver Disease	1
Drug Drug Interaction	1
Healthy Volunteer	1

Condition MeSH

Condition MeSH for IVACAFTOR; IVACAFTOR, TEZACAFTOR
Intervention	Trials
Cystic Fibrosis	42
Fibrosis	41
Bronchiectasis	1
Liver Diseases	1

Clinical Trial Locations for IVACAFTOR; IVACAFTOR, TEZACAFTOR

Trials by Country

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Trials by Country for IVACAFTOR; IVACAFTOR, TEZACAFTOR
Location	Trials
United States	474
Canada	30
Australia	24
United Kingdom	23
Germany	19

Trials by US State

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−

Trials by US State for IVACAFTOR; IVACAFTOR, TEZACAFTOR
Location	Trials
Massachusetts	20
California	20
North Carolina	20
Texas	20
Pennsylvania	20

Clinical Trial Progress for IVACAFTOR; IVACAFTOR, TEZACAFTOR

Clinical Trial Phase

Clinical Trial Phase for IVACAFTOR; IVACAFTOR, TEZACAFTOR
Clinical Trial Phase	Trials
Phase 4	5
Phase 3	29
Phase 2	7

Clinical Trial Status

Clinical Trial Status for IVACAFTOR; IVACAFTOR, TEZACAFTOR
Clinical Trial Phase	Trials
Completed	21
Active, not recruiting	8
Not yet recruiting	7

Clinical Trial Sponsors for IVACAFTOR; IVACAFTOR, TEZACAFTOR

Sponsor Name

Sponsor Name for IVACAFTOR; IVACAFTOR, TEZACAFTOR
Sponsor	Trials
Vertex Pharmaceuticals Incorporated	35
Proteostasis Therapeutics, Inc.	2
University of Alabama at Birmingham	2

Sponsor Type

Sponsor Type for IVACAFTOR; IVACAFTOR, TEZACAFTOR
Sponsor	Trials
Industry	39
Other	21

Ivacaftor and Tezacaftor: Clinical Trials, Market Analysis, and Projections

Introduction to Ivacaftor and Tezacaftor

Ivacaftor and tezacaftor are crucial medications in the treatment of cystic fibrosis (CF), a genetic disorder that affects the lungs, pancreas, and other organs. These drugs, often used in combination, have significantly improved the outcomes for patients with CF.

Clinical Trials Overview

Ivacaftor Clinical Trials

Ivacaftor, marketed as KALYDECO®, has been extensively studied in various clinical trials.

Trial 1 (STRIVE)

• This Phase 3 trial involved patients with CF aged 12 years and older who had the G551D mutation. The trial demonstrated significant improvements in lung function, as measured by the mean absolute change in percent predicted forced expiratory volume in one second (ppFEV₁) through 24 and 48 weeks. Patients receiving ivacaftor showed a +10.6 point improvement at 24 weeks and a +10.5 point improvement at 48 weeks compared to the placebo group[1].

Other Efficacy Endpoints

• In addition to lung function, ivacaftor showed improvements in the CFQ-R Respiratory Domain score, reduced the risk of pulmonary exacerbations by 60% at 24 weeks and 54% at 48 weeks, and increased body weight and reduced sweat chloride concentration[1].

Tezacaftor/Ivacaftor Combination Trials

The combination of tezacaftor and ivacaftor, known as SYMDEKO®, has also been evaluated in several clinical trials.

EXPAND Study

• This study involved patients with CF aged 12 and older who had one F508del mutation and a second mutation that results in residual CFTR function. The tezacaftor/ivacaftor combination demonstrated a mean absolute improvement in lung function of 6.8 percentage points compared to placebo. It also showed a 35% reduction in the annualized rate of pulmonary exacerbations and significant improvements in patient-reported outcomes, such as the CFQ-R Respiratory Domain score[3].

Safety and Tolerability

• The safety profile of the tezacaftor/ivacaftor combination was favorable, with most adverse events being mild or moderate. This combination was generally well-tolerated, similar to the findings in other studies[3].

Market Analysis and Projections

Current Market Status

The ivacaftor API market is a significant segment within the pharmaceutical industry, driven by the increasing demand for effective treatments for cystic fibrosis.

Key Players

• Major players in the ivacaftor API market include Vertex Pharmaceuticals Incorporated, Teva Pharmaceutical Industries Ltd., Cipla Limited, Mylan N.V., Hetero Drugs Limited, and others. These companies are driving innovation and competition in the market[2].

Market Segmentation

• The market is segmented by product type (oral dosage form, injectable dosage form, others) and by application (cystic fibrosis, others). The cystic fibrosis segment is the primary driver of the market[2].

Market Growth Projections

CAGR and Forecast

• The ivacaftor API market is projected to grow at a Compound Annual Growth Rate (CAGR) of 6.4% during the forecast period of 2024-2032. This growth is driven by increasing awareness, advancements in treatment options, and expanding patient populations[2].

Regional Analysis

• The market is analyzed across various regions including North America, Europe, Asia-Pacific, South America, and the Middle East and Africa. Each region presents unique opportunities and challenges, with North America and Europe being significant markets due to high healthcare spending and advanced healthcare infrastructure[2].

Clinical and Economic Impact

Clinical Outcomes

• The clinical trials have consistently shown that ivacaftor and the tezacaftor/ivacaftor combination significantly improve lung function, reduce pulmonary exacerbations, and enhance patient-reported outcomes. These improvements translate into better quality of life and reduced healthcare costs associated with hospitalizations and other treatments[1][3].

Economic Impact

• The economic impact of these drugs is substantial. By reducing the frequency of pulmonary exacerbations and hospitalizations, they lower the overall healthcare expenditure for CF patients. Additionally, the improved quality of life and increased productivity of patients contribute to economic benefits at a societal level.

Future Directions and Challenges

Emerging Treatments

• Ongoing research and development are focused on further improving CF treatments. For example, the Phase 2 trial of ELX-02 in combination with ivacaftor is exploring new therapeutic options for patients with specific mutations, such as the G542X allele[5].

Regulatory and Access Challenges

• Despite the clinical successes, access to these medications remains a challenge in many regions due to high costs and regulatory hurdles. Efforts to make these drugs more accessible and affordable are ongoing, involving both pharmaceutical companies and healthcare policymakers.

Patient Perspectives and Quality of Life

Patient-Reported Outcomes

• Clinical trials have shown significant improvements in patient-reported outcomes, such as the CFQ-R Respiratory Domain score. These improvements reflect better symptom management and an enhanced quality of life for patients with CF[1][3].

Real-World Evidence

• Real-world evidence supports the clinical trial findings, indicating that these medications are making a tangible difference in the lives of CF patients. Patient testimonials and long-term follow-up studies further underscore the positive impact of ivacaftor and tezacaftor.

Conclusion

Ivacaftor and the tezacaftor/ivacaftor combination have revolutionized the treatment of cystic fibrosis, offering significant clinical benefits and improving patient outcomes. As the market continues to grow, driven by increasing demand and advancements in treatment options, these medications are poised to remain critical components in the management of CF.

Key Takeaways

• Clinical Efficacy: Ivacaftor and the tezacaftor/ivacaftor combination have demonstrated significant improvements in lung function, reduced pulmonary exacerbations, and enhanced patient-reported outcomes.
• Market Growth: The ivacaftor API market is projected to grow at a CAGR of 6.4% from 2024 to 2032.
• Regional Analysis: The market is segmented across various regions, with North America and Europe being key markets.
• Future Directions: Ongoing research includes new therapeutic combinations and efforts to improve access to these medications.
• Patient Impact: These medications have significantly improved the quality of life for CF patients, as evidenced by clinical trials and real-world data.

FAQs

What is the primary indication for ivacaftor?

Ivacaftor is primarily indicated for the treatment of cystic fibrosis in patients who have at least one mutation in the CFTR gene that is responsive to the drug, such as the G551D mutation[1].

How does the tezacaftor/ivacaftor combination compare to ivacaftor monotherapy?

The tezacaftor/ivacaftor combination has shown statistically significant improvements in lung function and patient-reported outcomes compared to ivacaftor monotherapy, particularly in patients with specific CFTR mutations[3].

What is the projected market growth for the ivacaftor API market?

The ivacaftor API market is projected to grow at a CAGR of 6.4% during the forecast period of 2024-2032[2].

Which companies are major players in the ivacaftor API market?

Major players include Vertex Pharmaceuticals Incorporated, Teva Pharmaceutical Industries Ltd., Cipla Limited, Mylan N.V., and Hetero Drugs Limited, among others[2].

What are the common adverse events associated with the tezacaftor/ivacaftor combination?

The most common adverse events associated with the tezacaftor/ivacaftor combination are mild or moderate and include those typically seen in CF patients, with no significant safety concerns identified in clinical trials[3].

Sources

1. KALYDECO Clinical Trials: Clinical Trials for 12 Years or Older - KALYDECO® (ivacaftor)[1].
2. Ivacaftor API Market Report: Ivacaftor API Market to Set an Explosive Growth in Near Future[2].
3. Tezacaftor/Ivacaftor Combination Studies: Phase 3 Studies of the Tezacaftor/Ivacaftor Combination Treatment[3].
4. Clinical Trials Finder: Clinical Trials Finder - Find a Cystic Fibrosis Care Center[4].
5. ELX-02 Clinical Trial: NCT04135495 - Boston Children's Hospital[5].