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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03227471
• Date of registration: 18/07/2017
• Prospective Registration: No
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: A Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis
• Scientific title: A Phase 1/2 Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis
• Date of first enrolment: January 23, 2017
• Target sample size: 230
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03227471
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1/Phase 2

Countries of recruitment

Australia, Belgium, Netherlands, United States

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: Matched Placebo

Drug: IVA

Drug: TEZ/IVA

Drug: VX-445

Drug: VX-561

Drug: TEZ

Primary Outcome(s)

Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) [Parts D, E, and F only] [Time Frame: from baseline through Day 29]

Safety and tolerability as assessed by number of subjects with adverse events (AEs) and serious adverse events (SAEs) [Time Frame: from baseline through safety follow-up (up to 10 days after last dose for Part A, B, and C)]

Safety and tolerability as assessed by number of subjects with adverse events (AEs) and serious adverse events (SAEs) [Time Frame: from baseline through safety follow-up (up to 35 days after last dose for Parts D, E, and F).]

Secondary Outcome(s)

Observed pre-dose concentration (Ctrough) of VX-445, TEZ and metabolites (M1-TEZ and M2-TEZ), IVA and metabolites (M1-IVA and M6-IVA) and VX-561 [Time Frame: from Day 1 through Day 43]

Absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score [Parts D, E, and F only] [Time Frame: from baseline through Day 29]

Maximum observed concentration (Cmax) of VX-445,TEZ and metabolites (M1-TEZ and M2-TEZ), IVA and metabolites (M1-IVA and M6-IVA) and VX-561 [Time Frame: from Day 1 through Day 43]

Absolute change in sweat chloride concentrations [Parts C, D, E, and F only] [Time Frame: from baseline through Day 29]

Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-445, TEZ and metabolites (M1-TEZ and M2-TEZ), IVA and metabolites (M1-IVA and M6-IVA) and VX-561 [Time Frame: from Day 1 through Day 43]

Relative change in ppFEV1 [Parts D, E, and F only] [Time Frame: from baseline through Day 29]

Secondary ID(s)

2017-000797-11

VX16-445-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors