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Phase 3 Completed N=248 Randomized Triple-blind Treatment

A Phase 3 Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation

Source: ClinicalTrials.gov NCT02392234 ↗
Enrolled (actual)
248
Serious AEs
6.7%
Results posted
Jun 2018
Primary outcomePrimary: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Week 4 and Week 8 — -0.3; 4.4; 6.5 percentage of predicted FEV1 — p=< 0.0001
◆ Published Evidence
Highly cited
511citations · ~57 / year
Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis.
The New England journal of medicine · 2017 · Open access · Likely link

Summary

The purpose of this study is to evaluate the efficacy and safety of VX-661 in combination with ivacaftor (IVA, VX-770) and IVA monotherapy in participants with Cystic Fibrosis (CF) who are heterozygous for F508del-CFTR allele and a second allele with a CFTR mutation predicted to have residual function.

Linked Publications (4)

  • Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis.
    The New England journal of medicine · 2017 · 511 citations · Open access · Likely link
  • Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).
    The Cochrane database of systematic reviews · 2020 · 71 citations · Open access · Likely link
  • Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).
    The Cochrane database of systematic reviews · 2023 · 22 citations · Open access · Likely link
  • Development of the Cystic Fibrosis Questionnaire-Revised-8 Dimensions: Estimating Utilities From the Cystic Fibrosis Questionnaire-Revised.
    Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research · 2023 · 13 citations · Open access · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Week 4 and Week 8
-0.3; 4.4; 6.5 < 0.0001 sig
SECONDARY
Absolute Change From Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Week 4 and Week 8
-1.0; 8.7; 10.1 <0.0001 sig
SECONDARY
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
126; 114; 117; 14; 10; 8
SECONDARY
Relative Change From Study Baseline in ppFEV1 at Average of Week 4 and Week 8
-0.2; 7.9; 11.2 <0.0001 sig
SECONDARY
Absolute Change From Study Baseline in Sweat Chloride at Average of Week 4 and Week 8
-0.4; -4.9; -9.9 <0.0001 sig
SECONDARY
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661), IVA and IVA Metabolite (M1 IVA) After Administration of VX-661/IVA Combination Therapy
2370; 5230; 909; 2010
SECONDARY
Ctrough of IVA and IVA Metabolite (M1 IVA) After Administration of IVA Monotherapy
696; 1550

Eligibility Criteria

Inclusion Criteria

  • Heterozygous for F508del-CFTR and a second allele with a CFTR mutation predicted to have residual function
  • Forced Expiratory Volume in 1 Second (FEV1) greater than or equal to (≥) 40 percent (%) and less than or equal to (≤) 90% of predicted normal for age, sex, and height during screening
  • Sweat chloride value ≥60 millimole per liter (mmol/L) during screening OR as documented in the participant's medical record
  • Stable CF disease as judged by the investigator

Exclusion Criteria

  • History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant
  • An acute upper or lower respiratory infection, pulmonary exacerbation
  • History of solid organ or hematological transplantation
  • Ongoing or prior participation in an investigational drug study (including studies investigating VX-661, lumacaftor [VX-809], and/or ivacaftor) within 30 days of screening
  • Pregnant and nursing females
  • Sexually active participants of reproductive potential who are not willing to follow the contraception requirements
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02392234) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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