A Study Evaluating the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis

Vertex Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Cystic Fibrosis

Treatments: Drug: VX-152; Drug: TEZ/IVA; Drug: Placebo; Drug: IVA

Study type: Interventional

Funder types: Industry

Identifiers

NCT02951195

VX16-152-102

Details and patient eligibility

About

This is a Phase 2, randomized, double blind, placebo and active-controlled, parallel group, multicenter study designed to evaluate the safety and tolerability of VX-152 in Triple Combination (TC) with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF), or who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F508del/F508del).

Enrollment: 80 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Willing and able to comply with scheduled visits, treatment pan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.

• Body weight ≥35 kg.

• Sweat chloride value ≥ 60 mmol/L from test results obtained during screening.

• Subjects must have an eligible CFTR genotype:

  • Cohorts 1A, 1B, 1C: Heterozygous for F508del and a minimal function mutation known or predicted not to respond to TEZ and/or IVA.
  • Cohorts 2A, 2B: Homozygous for F508del.

• Subjects must have an FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height at the Screening Visit.

• Stable CF disease as judged by the investigator.

• Willing to remain on a stable CF medication regimen through the planned end of treatment or if applicable the Safety Follow-up Visit.

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 subject.
• History of cirrhosis with portal hypertension.
• Risk factors for Torsade de Pointes.
• History of hemolysis.
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.
• Clinically significant abnormal laboratory values at screening.
• An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before the first dose of study drug.
• Lung infection with organisms associated with a more rapid decline in pulmonary status.
• An acute illness not related to CF within 14 days before the first dose of study drug.
• A standard digital ECG demonstrating QTc >450 msec at screening.
• History of solid organ or hematological transplantation.
• History or evidence of cataract or lens opacity determined to be clinically significant by the ophthalmologist or optometrist, based on the ophthalmologic examination during the Screening Period.
• History of alcohol or drug abuse in the past year, including but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator.
• Ongoing or prior participation in an investigational drug study with certain exceptions.
• Use of commercially available CFTR modulator within 14 days before screening (applies only to Cohorts 1A, 1B, and 1C).
• Pregnant or nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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80 participants in 8 patient groups, including a placebo group

Part 1: Placebo

Placebo Comparator group

Treatment:

Drug: Placebo

Drug: Placebo

Part 1 Cohort 1A: TC

Experimental group

Treatment:

Drug: IVA

Drug: TEZ/IVA

Drug: VX-152

Part 1 Cohort 1B: TC

Experimental group

Treatment:

Drug: IVA

Drug: TEZ/IVA

Drug: VX-152

Part 1 Cohort 1C: TC

Experimental group

Treatment:

Drug: IVA

Drug: TEZ/IVA

Drug: VX-152

Part 2 Cohort 2A: TEZ/IVA

Active Comparator group

Treatment:

Drug: Placebo

Drug: IVA

Drug: TEZ/IVA

Drug: Placebo

Part 2 Cohort 2A: TC

Experimental group

Treatment:

Drug: IVA

Drug: TEZ/IVA

Drug: VX-152

Part 2 Cohort 2B: TEZ/IVA

Active Comparator group

Treatment:

Drug: Placebo

Drug: IVA

Drug: TEZ/IVA

Drug: Placebo

Part 2 Cohort 2B: TC

Experimental group

Treatment:

Drug: IVA

Drug: TEZ/IVA

Drug: VX-152