FindTrial
Sign In

Evaluation of VX-659/TEZ/IVA in Cystic Fibrosis Subjects 6 Through 11 Years of Age

A Phase 3 Study Evaluating the Pharmacokinetics, Safety, and Tolerability of VX-659/TEZ/IVA Triple Combination Therapy in Cystic Fibrosis Subjects 6 Through 11 Years of Age

Status
Terminated
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03633526
Enrollment
18
Registered
2018-08-16
Start date
2018-08-03
Completion date
2019-01-18
Last updated
2020-02-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cystic Fibrosis

Brief summary

This study will evaluate the pharmacokinetics (PK), safety, tolerability, efficacy, and pharmacodynamic effect of VX-659, tezacaftor (TEZ), and ivacaftor (IVA) when dosed in triple combination (TC) in Cystic Fibrosis (CF) subjects with F/F or F/MF genotypes. The study was discontinued after completion of Part A due to Sponsor's discretion.

Interventions

DRUGVX-659/TEZ/IVA

VX-659/TEZ/IVA FDC tablet.

DRUGIVA

IVA mono tablet.

Sponsors

Vertex Pharmaceuticals Incorporated
Lead SponsorINDUSTRY

Study design

Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
6 Years to 11 Years
Healthy volunteers
No

Inclusion criteria

Key Inclusion Criteria: * Homozygous or heterozygous for F508del mutation (F/F or F/MF genotypes) * Forced expiratory volume in 1 second (FEV1) value ≥40% of predicted mean for age, sex, and height. Key

Exclusion criteria

* Clinically significant cirrhosis with or without portal hypertension * Lung infection with organisms associated with a more rapid decline in pulmonary status. * Solid organ or hematological transplantation. Other protocol defined Inclusion/

Design outcomes

Primary

MeasureTime frame
Maximum Observed Concentration (Cmax) of VX-659, TEZ, and IVADay 1 and Day 15
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, and IVADay 8 and Day 15
Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of VX-659, TEZ, and IVADay 1 and Day 15

Secondary

MeasureTime frame
Maximum Observed Concentration (Cmax) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)Day 1 and Day 15
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)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 6 weeks)
Observed Pre-Dose Concentration (Ctrough) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)Day 8 and Day 15
Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)Day 1 and Day 15

Countries

United States

Participant flow

Recruitment details

A total of 18 participants were enrolled in this study. Two participants were enrolled but were not dosed in triple combination (TC) treatment period. Therefore, results are reported for 16 participants.

Pre-assignment details

This study was conducted in participants with cystic fibrosis (CF) 6-11 years of age. The study was terminated before start of Part B at Sponsor's discretion.

Participants by arm

ArmCount
VX-659/TEZ/IVA
Participants who received VX-659 120 mg/TEZ 50 mg/ IVA 75 mg as FDC in the morning and IVA 75 mg as a mono tablet in the evening for 15 days in the TC treatment period.
16
Total16

Baseline characteristics

CharacteristicVX-659/TEZ/IVA
Age, Continuous9.2 years
STANDARD_DEVIATION 1.4
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
14 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
Race (NIH/OMB)
Asian
0 Participants
Race (NIH/OMB)
Black or African American
0 Participants
Race (NIH/OMB)
More than one race
0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
Race (NIH/OMB)
White
16 Participants
Sex: Female, Male
Female
5 Participants
Sex: Female, Male
Male
11 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
0 / 16
other
Total, other adverse events
13 / 16
serious
Total, serious adverse events
1 / 16

Outcome results

Primary

Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of VX-659, TEZ, and IVA

Time frame: Day 1 and Day 15

Population: PK set. Here Number analyzed signifies those participants who were evaluable at specified timepoints.

ArmMeasureGroupValue (MEAN)Dispersion
VX-659/TEZ/IVAArea Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of VX-659, TEZ, and IVAVX-659: Day 15.41 hour*mcg/mL (h*mcg/mL)Standard Deviation 3.65
VX-659/TEZ/IVAArea Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of VX-659, TEZ, and IVAVX-659: Day 158.55 hour*mcg/mL (h*mcg/mL)Standard Deviation 4.5
VX-659/TEZ/IVAArea Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of VX-659, TEZ, and IVATEZ: Day 115.5 hour*mcg/mL (h*mcg/mL)Standard Deviation 5.36
VX-659/TEZ/IVAArea Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of VX-659, TEZ, and IVATEZ: Day 1519.3 hour*mcg/mL (h*mcg/mL)Standard Deviation 7.26
VX-659/TEZ/IVAArea Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of VX-659, TEZ, and IVAIVA: Day 11.64 hour*mcg/mL (h*mcg/mL)Standard Deviation 0.795
VX-659/TEZ/IVAArea Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of VX-659, TEZ, and IVAIVA: Day 152.95 hour*mcg/mL (h*mcg/mL)Standard Deviation 1.18
Primary

Maximum Observed Concentration (Cmax) of VX-659, TEZ, and IVA

Time frame: Day 1 and Day 15

Population: Pharmacokinetic (PK) set included participants who received at least 1 dose of study drug and for whom the primary PK data were considered to be sufficient and interpretable. Here Number analyzed signifies those subjects who were evaluable at the specified timepoint.

ArmMeasureGroupValue (MEAN)Dispersion
VX-659/TEZ/IVAMaximum Observed Concentration (Cmax) of VX-659, TEZ, and IVATEZ: Day 14.53 microgram per milliliter (mcg/mL)Standard Deviation 1.65
VX-659/TEZ/IVAMaximum Observed Concentration (Cmax) of VX-659, TEZ, and IVATEZ: Day 155.22 microgram per milliliter (mcg/mL)Standard Deviation 1.69
VX-659/TEZ/IVAMaximum Observed Concentration (Cmax) of VX-659, TEZ, and IVAIVA: Day 10.536 microgram per milliliter (mcg/mL)Standard Deviation 0.208
VX-659/TEZ/IVAMaximum Observed Concentration (Cmax) of VX-659, TEZ, and IVAIVA: Day 150.733 microgram per milliliter (mcg/mL)Standard Deviation 0.256
VX-659/TEZ/IVAMaximum Observed Concentration (Cmax) of VX-659, TEZ, and IVAVX-659: Day 11.81 microgram per milliliter (mcg/mL)Standard Deviation 0.858
VX-659/TEZ/IVAMaximum Observed Concentration (Cmax) of VX-659, TEZ, and IVAVX-659: Day 152.55 microgram per milliliter (mcg/mL)Standard Deviation 1.21
Primary

Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, and IVA

Time frame: Day 8 and Day 15

Population: PK set. Here Number analyzed signifies those participants who were evaluable at specified timepoints.

ArmMeasureGroupValue (MEAN)Dispersion
VX-659/TEZ/IVAObserved Pre-Dose Concentration (Ctrough) of VX-659, TEZ, and IVAVX-659: Day 80.358 mcg/mLStandard Deviation 0.259
VX-659/TEZ/IVAObserved Pre-Dose Concentration (Ctrough) of VX-659, TEZ, and IVAVX-659: Day 150.367 mcg/mLStandard Deviation 0.283
VX-659/TEZ/IVAObserved Pre-Dose Concentration (Ctrough) of VX-659, TEZ, and IVATEZ: Day 80.897 mcg/mLStandard Deviation 0.488
VX-659/TEZ/IVAObserved Pre-Dose Concentration (Ctrough) of VX-659, TEZ, and IVATEZ: Day 150.740 mcg/mLStandard Deviation 0.421
VX-659/TEZ/IVAObserved Pre-Dose Concentration (Ctrough) of VX-659, TEZ, and IVAIVA: Day 80.289 mcg/mLStandard Deviation 0.195
VX-659/TEZ/IVAObserved Pre-Dose Concentration (Ctrough) of VX-659, TEZ, and IVAIVA: Day 150.283 mcg/mLStandard Deviation 0.241
Secondary

Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)

Time frame: Day 1 and Day 15

Population: PK set. Here Number analyzed signifies those participants who were evaluable at specified timepoints.

ArmMeasureGroupValue (MEAN)Dispersion
VX-659/TEZ/IVAArea Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)M1-TEZ: Day 15.52 h*mcg/mLStandard Deviation 2.87
VX-659/TEZ/IVAArea Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)M1-TEZ: Day 1525.2 h*mcg/mLStandard Deviation 7.7
VX-659/TEZ/IVAArea Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)M1-IVA: Day 13.60 h*mcg/mLStandard Deviation 1.87
VX-659/TEZ/IVAArea Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)M1-IVA: Day 156.98 h*mcg/mLStandard Deviation 2.94
Secondary

Maximum Observed Concentration (Cmax) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)

Time frame: Day 1 and Day 15

Population: PK set. Here Number analyzed signifies those subjects who were evaluable at the specified timepoint.

ArmMeasureGroupValue (MEAN)Dispersion
VX-659/TEZ/IVAMaximum Observed Concentration (Cmax) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)M1-TEZ: Day 11.63 mcg/mLStandard Deviation 0.553
VX-659/TEZ/IVAMaximum Observed Concentration (Cmax) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)M1-TEZ: Day 155.04 mcg/mLStandard Deviation 1.27
VX-659/TEZ/IVAMaximum Observed Concentration (Cmax) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)M1-IVA: Day 11.25 mcg/mLStandard Deviation 0.449
VX-659/TEZ/IVAMaximum Observed Concentration (Cmax) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)M1-IVA: Day 151.73 mcg/mLStandard Deviation 0.741
Secondary

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

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 6 weeks)

Population: Safety set included all participants who received at least 1 dose of study drug.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
VX-659/TEZ/IVANumber of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)Participants with AEs13 Participants
VX-659/TEZ/IVANumber of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)Participants with SAEs1 Participants
Secondary

Observed Pre-Dose Concentration (Ctrough) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)

Time frame: Day 8 and Day 15

Population: PK set. Here Number analyzed signifies those participants who were evaluable at specified timepoints.

ArmMeasureGroupValue (MEAN)Dispersion
VX-659/TEZ/IVAObserved Pre-Dose Concentration (Ctrough) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)M1-TEZ: Day 83.56 mcg/mLStandard Deviation 1.33
VX-659/TEZ/IVAObserved Pre-Dose Concentration (Ctrough) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)M1-TEZ: Day 153.35 mcg/mLStandard Deviation 1.23
VX-659/TEZ/IVAObserved Pre-Dose Concentration (Ctrough) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)M1-IVA: Day 80.816 mcg/mLStandard Deviation 0.491
VX-659/TEZ/IVAObserved Pre-Dose Concentration (Ctrough) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)M1-IVA: Day 150.858 mcg/mLStandard Deviation 0.672

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026