Clinical trial NCT02951195: A Study Evaluating the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis
Official title: A Phase 2, Randomized, Double Blind, Controlled Study to Evaluate the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2016-11-01
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 Through Safety Follow-up Visit (Up to Day 43 for Part 1 and Day 71 for Part 2)
measure: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A
timeFrame: From Baseline at Day 15
measure: Absolute Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B
timeFrame: From Baseline Through Day 29
Secondary outcomes:
measure: Absolute Change in Sweat Chloride Concentrations at Day 15 for Part 1 and Part 2 Cohort 2A
timeFrame: From Baseline at Day 15
measure: Absolute Change in Sweat Chloride Concentrations Through Day 29 for Part 2 Cohort 2B
timeFrame: From Baseline Through Day 29
measure: Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A
timeFrame: From Baseline at Day 15
measure: Relative Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B
timeFrame: From Baseline Through Day 29
measure: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 15 for Part 1 and Part 2 Cohort 2A
timeFrame: From Baseline at Day 15
measure: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 29 for Part 2 Cohort 2B
timeFrame: From Baseline at Day 29
measure: Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA
timeFrame: Pre-dose at Day 8, Day 15 and Day 29
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Orlando
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Peoria
country: United States
state: Illinois
city: Saint Louis
country: United States
state: Missouri
city: Chapel Hill
country: United States
state: North Carolina
city: Akron
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Madison
country: United States
state: Wisconsin
Study officials:
References: