Phase 2
Completed N=225
A Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis
Source: ClinicalTrials.gov NCT03227471 ↗Enrolled (actual)
225
Serious AEs
3.1%
Results posted
Jan 2022
Primary outcomePrimary: Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) — 0; 3; 1; 2 Participants
Summary
This is a first-in-human and proof-of-concept study of VX-445. The study includes 6 parts. Parts A, B, and C were conducted in healthy subjects. Parts D, E, and F were conducted in subjects with Cystic Fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F/F genotype), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ, IVA, or TEZ/IVA (F/MF genotypes).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
0; 3; 1; 2; 2; 2 | — |
| PRIMARY Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
12; 49; 5; 19; 7; 19 | — |
| PRIMARY Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) |
0.0; 11.1; 7.9; 13.8 | 0.9943 |
| PRIMARY Part E: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) |
0.4; 11.0 | 0.8869 |
| PRIMARY Part F: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) |
1.2; 11.7 | 0.6407 |
| SECONDARY Part A: Maximum Observed Concentration (Cmax) of VX-445 |
0.398; 0.989; 2.52; 4.56; 7.07; 0.486 | — |
| SECONDARY Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 |
11.4; 30.8; 87.1; 125; 286; 21.8 | — |
| SECONDARY Part B: Maximum Observed Concentration (Cmax) of VX-445 |
1.18; 2.82; 3.47; 9.56; 2.13; 5.83 | — |
| SECONDARY Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 |
17.9; 42.2; 57.9; 119; 61.4; 183 | — |
| SECONDARY Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445 |
1.05; 2.81; 7.10; 11.5 | — |
| SECONDARY Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) |
3.04; 4.86; 1.72; 8.29; 10.3; 3.58 | — |
| SECONDARY Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) |
48.6; 72.5; 26.4; 156; 177; 65.4 | — |
| SECONDARY Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) |
425; 461; 437; 1290; 1190; 1070 | — |
| SECONDARY Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) |
6350; 6210; 5480; 21600; 18800; 16900 | — |
| SECONDARY Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) |
4.63; 5.91; 2.09; 4.45; 7.60; 2.92 | — |
| SECONDARY Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) |
753; 759; 604; 610; 990; 881 | — |
| SECONDARY Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) |
1.04; 2.15; 5.77; 1.27; 2.18; 5.57 | — |
| SECONDARY Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) |
5.07; 5.35; 1.85; 1.86; 1.84; 1.99 | — |
| SECONDARY Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561 |
4.40; 5.25; 1.80; 2.22; 4.99; 5.09 | — |
| SECONDARY Part D: Absolute Change in Sweat Chloride Concentration |
-2.2; -38.2; -33.2; -39.1 | 0.5802 |
| SECONDARY Part E: Absolute Change in Sweat Chloride Concentration |
0.8; -39.6 | 0.8712 |
| SECONDARY Part F: Absolute Change in Sweat Chloride Concentration |
1.0; -33.6 | 0.8359 |
| SECONDARY Part D: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) |
0.3; 19.3; 13.8; 26.2 | 0.9453 |
| SECONDARY Part E: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) |
1.4; 19.2 | 0.7849 |
| SECONDARY Part F: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) |
1.6; 19.9 | 0.7356 |
| SECONDARY Part D: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score |
4.2; 20.8; 15.4; 25.7 | 0.3940 |
| SECONDARY Part E: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score |
5.2; 20.7 | 0.4757 |
| SECONDARY Part F: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score |
20.2; 20.2 | 0.0070 sig |
Eligibility Criteria
Key Inclusion Criteria
Parts A, B, and C:
- Female subjects must be of non-childbearing potential.
- Between the ages of 18 and 55 years, inclusive.
- Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, and a total body weight >50 kg
Parts D, E, and F:
- Body weight ≥35 kg.
- Subjects must have an eligible CFTR genotype:
- Parts D and F: Heterozygous for F508del and an MF mutation (F/MF)
- Part E: Homozygous for F508del (F/F)
- FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height.
Key Exclusion Criteria
Parts A, B, and C:
- Any condition possibly affecting drug absorption.
- History of febrile illness within 14 days before the first study drug dose.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Parts D, E, and F:
- History of clinically significant cirrhosis with or without portal hypertension.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- Lung infection with organisms associated with a more rapid decline in pulmonary status.
- History of solid organ or hematological transplantation.
Other protocol defined Inclusion/Exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT03227471). 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.