NCT03559062

A Study to Evaluate Efficacy and Safety of TEZ/IVA in Subjects Aged 6 Through 11 Years With Cystic Fibrosis

Completed Phase 3 Results posted Last updated 11 February 2020

What this trial tests

Phase 3 trial testing TEZ/IVA in Cystic Fibrosis in 67 participants. Completed in 21 December 2018.

Timeline

17 May 2018

Primary endpoint
21 December 2018

21 December 2018

Quick facts

Lead sponsor	Vertex Pharmaceuticals Incorporated
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	67
Start date	17 May 2018
Primary completion	21 December 2018
Estimated completion	21 December 2018
Sites	27 locations across Denmark, France, Belgium, Ireland, United Kingdom, Germany, Poland, Switzerland

Drugs / interventions tested

• TEZ/IVA — full drug profile →
• IVA — full drug profile →
• Placebo
• Placebo

Conditions studied

• Cystic Fibrosis — all drugs for Cystic Fibrosis →

Sponsor

Vertex Pharmaceuticals Incorporated — full company profile →

Who can join

Adults 6 to 11, any sex, with Cystic Fibrosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Absolute Change in Lung Clearance Index 2.5 (LCI2.5) Through Week 8 Primary · From baseline through Week 8

LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.

Group	Value	95% CI
TEZ/IVA	-0.51	± 0.11

Absolute Change in Sweat Chloride At Week 8 Secondary · From baseline at Week 8

Sweat samples were collected using an approved collection device.

Group	Value	95% CI
TEZ/IVA	-12.3	± 1.5

Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8 Secondary · From baseline through Week 8

The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

Group	Value	95% CI
TEZ/IVA	2.3	± 1.2

Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) up to Safety Follow-up Visit Secondary · From first dose of study drug up to safety follow-up visit (up to Week 12)

Participants with AEs

Group	Value	95% CI
Placebo	8
TEZ/IVA	41
Ivacaftor	2

Participants with SAEs

Group	Value	95% CI
Placebo	0
TEZ/IVA	0
Ivacaftor	0

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug up to safety follow-up visit (up to Week 12). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 0/10 (0%)

Deaths: 0/10

TEZ/IVA

Serious: 0/54 (0%)

Deaths: 0/54

Ivacaftor

Serious: 0/3 (0%)

Deaths: 0/3

Other adverse events (25 terms — click to expand)

Reaction	System	Placebo	TEZ/IVA	Ivacaftor
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Productive cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Gastroenteritis	Infections and infestations	—	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Infective pulmonary exacerbation of cystic fibrosis	Infections and infestations	—	—	—
Thermal burn	Injury, poisoning and procedural complications	—	—	—
Arthropod bite	Injury, poisoning and procedural complications	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—
Sputum increased	Respiratory, thoracic and mediastinal disorders	—	—	—
Throat irritation	Respiratory, thoracic and mediastinal disorders	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—
Blister	Skin and subcutaneous tissue disorders	—	—	—
Arthritis	Musculoskeletal and connective tissue disorders	—	—	—
Bacterial disease carrier	Infections and infestations	—	—	—
Otitis media	Infections and infestations	—	—	—
Rhinitis	Infections and infestations	—	—	—
Impetigo	Infections and infestations	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Viral upper respiratory tract infection	Infections and infestations	—	—	—

Data from ClinicalTrials.gov NCT03559062 adverse events section.

Sponsor's own description

This study will evaluate the efficacy of tezacaftor in combination with ivacaftor (TEZ/IVA) in participants with cystic fibrosis (CF) aged 6 through 11 years, who are homozygous for the F508del mutation (F/F) or heterozygous for F508del with an eligible residual function mutation (F/RF).

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. The impact of FDA and EMA regulatory decision-making process on the access to CFTR modulators for the treatment of cystic fibrosis.
   Costa E, Girotti S, Pauro F, Leufkens HGM, et al · · 2022 · cited 43× · PMID 35525974 · DOI 10.1186/s13023-022-02350-5
2. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).
   Southern KW, Murphy J, Sinha IP, Nevitt SJ. · · 2020 · cited 32× · PMID 33331662 · DOI 10.1002/14651858.cd010966.pub3