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NCT03525548

A Study of VX-445 Combination Therapy in CF Subjects Homozygous for F508del (F/F)

Completed Phase 3 Results posted Last updated 27 January 2020
What this trial tests

Phase 3 trial testing VX-445/TEZ/IVA in Cystic Fibrosis in 113 participants. Completed in 28 December 2018.

Timeline
3 August 2018
Primary endpoint
28 December 2018
28 December 2018

Quick facts

Lead sponsorVertex Pharmaceuticals Incorporated
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment113
Start date3 August 2018
Primary completion28 December 2018
Estimated completion28 December 2018
Sites44 locations across Belgium, United Kingdom, Netherlands, United States

Drugs / interventions tested

Conditions studied

Sponsor

Vertex Pharmaceuticals Incorporated — full company profile →

Who can join

12 and older, 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 Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Primary · From Baseline at Week 4

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

GroupValue95% CI
TEZ/IVA0.4± 0.9
VX-445/TEZ/IVA TC10.4± 0.9
Absolute Change in Sweat Chloride (SwCl) Secondary · From Baseline at Week 4

Sweat samples were collected using an approved collection device.

GroupValue95% CI
TEZ/IVA1.7± 1.8
VX-445/TEZ/IVA TC-43.4± 1.7
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Secondary · From Baseline at Week 4

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 indicate fewer symptoms and better health-related quality of life.

GroupValue95% CI
TEZ/IVA-1.4± 2.0
VX-445/TEZ/IVA TC16.0± 2.0
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Secondary · From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
Participants with AEs
GroupValue95% CI
TEZ/IVA33
VX-445/TEZ/IVA TC32
Participants with SAEs
GroupValue95% CI
TEZ/IVA1
VX-445/TEZ/IVA TC2
Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA Secondary · Day 1 and Week 4
VX-445: Day 1
GroupValue95% CI
VX-445/TEZ/IVA TCNA± NA
VX-445: Week 4
GroupValue95% CI
VX-445/TEZ/IVA TC4.84± 2.59
TEZ: Day 1
GroupValue95% CI
TEZ/IVA1.71± 0.942
VX-445/TEZ/IVA TC1.60± 1.03
TEZ: Week 4
GroupValue95% CI
TEZ/IVA1.48± 0.829
VX-445/TEZ/IVA TC1.89± 0.974
M1-TEZ: Day 1
GroupValue95% CI
TEZ/IVA4.84± 1.71
VX-445/TEZ/IVA TC4.76± 1.78
M1-TEZ: Week 4
GroupValue95% CI
TEZ/IVA4.86± 1.74
VX-445/TEZ/IVA TC5.28± 2.04
IVA: Day 1
GroupValue95% CI
TEZ/IVA0.652± 0.399
VX-445/TEZ/IVA TC0.598± 0.428
IVA: Week 4
GroupValue95% CI
TEZ/IVA0.530± 0.297
VX-445/TEZ/IVA TC0.652± 0.542

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

TEZ/IVA
Serious: 1/52 (2%)
Deaths: 0/52
VX-445/TEZ/IVA TC
Serious: 2/55 (4%)
Deaths: 0/55

Serious adverse events (2 terms)

ReactionSystemTEZ/IVAVX-445/TEZ/IVA TC
Infective pulmonary exacerbation of cystic fibrosisInfections and infestations
RashSkin and subcutaneous tissue disorders
Other adverse events (14 terms — click to expand)

ReactionSystemTEZ/IVAVX-445/TEZ/IVA TC
CoughRespiratory, thoracic and mediastinal disorders
HaemoptysisRespiratory, thoracic and mediastinal disorders
Infective pulmonary exacerbation of cystic fibrosisInfections and infestations
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
NasopharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
HeadacheNervous system disorders
Sputum increasedRespiratory, thoracic and mediastinal disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
Respiration abnormalRespiratory, thoracic and mediastinal disorders
DiarrhoeaGastrointestinal disorders
Abdominal painGastrointestinal disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders

Most-reported serious reactions: Infective pulmonary exacerbation of cystic fibrosis, Rash.

Data from ClinicalTrials.gov NCT03525548 adverse events section.

Sponsor's own description

This study will evaluate the efficacy of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation (F/F)

Publications & conference data

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

  1. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial.
    Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, et al · · 2019 · cited 1038× · PMID 31679946 · DOI 10.1016/s0140-6736(19)32597-8
  2. VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles.
    Keating D, Marigowda G, Burr L, Daines C, et al · · 2018 · cited 561× · PMID 30334692 · DOI 10.1056/nejmoa1807120
  3. CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine.
    Lopes-Pacheco M. · · 2019 · cited 349× · PMID 32153386 · DOI 10.3389/fphar.2019.01662
  4. Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor for 24 Weeks or Longer in People with Cystic Fibrosis and One or More <i>F508del</i> Alleles: Interim Results of an Open-Label Phase 3 Clinical Trial.
    Griese M, Costa S, Linnemann RW, Mall MA, et al · · 2021 · cited 140× · PMID 32969708 · DOI 10.1164/rccm.202008-3176le
  5. Clinical development of triple-combination CFTR modulators for cystic fibrosis patients with one or two <i>F508del</i> alleles.
    Taylor-Cousar JL, Mall MA, Ramsey BW, McKone EF, et al · · 2019 · cited 87× · PMID 31218221 · DOI 10.1183/23120541.00082-2019
  6. A Review of Trikafta: Triple Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulator Therapy.
    Zaher A, ElSaygh J, Elsori D, ElSaygh H, et al · · 2021 · cited 62× · PMID 34268058 · DOI 10.7759/cureus.16144
  7. Long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis and at least one <i>F508del</i> allele: 144-week interim results from a 192-week open-label extension study.
    Daines CL, Tullis E, Costa S, Linnemann RW, et al · · 2023 · cited 61× · PMID 37945033 · DOI 10.1183/13993003.02029-2022
  8. 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

Verify or expand the search:

Other trials of VX-445/TEZ/IVA

Trials testing the same drug.

Other recruiting trials for Cystic Fibrosis

Currently open trials in the same condition.

Other Vertex Pharmaceuticals Incorporated trials

Trials by the same sponsor.

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