A Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis

A Phase 1/2 Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis

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).

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.