A Study Evaluating the Safety and Efficacy of VX-440 Combination Therapy in Subjects With Cystic Fibrosis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02951182
• Date of registration: 26/10/2016
• Prospective Registration: No
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: A Study Evaluating the Safety and Efficacy of VX-440 Combination Therapy in Subjects With Cystic Fibrosis
• Scientific title: A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of VX-440 Combination Therapy in Subjects Aged 12 Years and Older With Cystic Fibrosis
• Date of first enrolment: October 2016
• Target sample size: 74
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02951182
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Australia, Austria, Belgium, Canada, Denmark, Germany, Italy, Spain, United Kingdom, United States

Key inclusion & exclusion criteria

Inclusion Criteria:

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

- To prevent pregnancy, female participants of childbearing potential and their male
partners will be required to use pre-specified, highly effective methods of
non-hormonal contraception. Male participants with female partners of childbearing
potential will be required to use a condom.

- Body weight =35 kg.

- Sweat chloride value =60 mmol/L from test results obtained during screening.

- Subjects must have an eligible CFTR genotype:

- Heterozygous for F508del and a minimal function (MF) mutation known or predicted
not to be responsive to TEZ and/or IVA.

- 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. (e.g., ongoing participation in NCT02565914)

- Use of commercially available CFTR modulator (e.g., Kalydeco, Orkambi) within 14 days
before screening (applies only to the Heterozygous F508del/MF cohorts; does not apply
to the Homozygous F508del/F508del Cohort).

- Pregnant or nursing females: Females of childbearing potential must have a negative
pregnancy test at screening and Day 1.



Age minimum: 12 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

Drug: VX-440

Primary Outcome(s)

Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [Time Frame: From Baseline through Day 29]

Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: From first dose of Study Drug in the Treatment Period through Safety Follow-up Visit (Up to Day 57 for Part 1 and Day 85 for Part 2)]

Secondary Outcome(s)

Pre-dose Plasma Concentration (Ctrough) of VX-440, TEZ, M1-TEZ, IVA and M1-IVA [Time Frame: Predose at Day 8, Day 15 and Day 29]

Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score [Time Frame: From Baseline at Day 29]

Relative Change in ppFEV1 [Time Frame: From Baseline through Day 29]

Absolute Change in Sweat Chloride Concentrations [Time Frame: From Baseline through Day 29]

Secondary ID(s)

2016-000454-36

VX15-440-101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 28/08/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02951182