A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)
- Conditions
- Cystic fibrosis10083624
- Registration Number
- NL-OMON49493
- Lead Sponsor
- Vertex Pharmaceuticals
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 12
1. Subject (or his or her legally appointed and authorized representative) will
sign and date an informed consent form (ICF), and, when appropriate, an assent
form.
2. Willing and able to comply with scheduled visits, treatment plan, study
restrictions, laboratory tests, contraceptive guidelines, and other study
procedures.
3. Age 12 years or older, at the date of informed consent.
4. Confirmed diagnosis of CF as determined by the investigator.
5. Subject is heterozygous for F508del and either a gating or residual function
mutation (F/G and F/RF genotypes) and is in a region where their genotype and
age group are approved indications for treatment with IVA and/or TEZ/IVA (see
Appendix A for qualifying mutations).
6. Forced expiratory volume in 1 second (FEV1) value *40% and *90% of predicted
mean for age, sex, race, and height (equations of the Global Lung Function
Initiative [GLI]) at the Screening Visit. Spirometry measurements must meet
American Thoracic Society/European Respiratory Society criteria for
acceptability and repeatability.
7. Subjects must be able to produce a valid (quantity-sufficient) sweat sample
at screening.
8. Stable CF disease as judged by the investigator.
9. Willing to remain on a stable CF treatment regimen through completion of
study participation.
1. History of any illness or any clinical condition that, in the opinion of the
investigator, might confound the results of the study or pose an additional
risk in administering study drug(s) to the subject. This includes, but is not
limited to, the following
- Clinically significant cirrhosis with or without portal hypertension.
- Solid organ or hematological transplantation.
- Alcohol or drug abuse in the past year, including, but not limited to,
cannabis, cocaine, and opiates, as deemed by the investigator.
- Cancer, except for squamous cell skin cancer, basal cell skin cancer, and
Stage 0 cervical carcinoma in situ (each being disease-free for the last 5
years).
2. Any of the following abnormal laboratory values at screening.
- Hemoglobin <10 g/dL
- Total bilirubin *2 × upper limit of normal (ULN)
- Aspartate transaminase (AST), alanine transaminase (ALT), or gamma-glutamyl
transferase (GGT) *3 × ULN
- Abnormal renal function defined as estimated glomerular filtration rate *50
mL/min/1.73 m^2 (calculated by the Modification of Diet in Renal Disease Study
Equation) for subjects *18 years of age, or *45 mL/min/1.73 m^2 (calculated by
the Counahan-Barratt equation) for subjects 12 to 17 years of age (inclusive)
3. An acute upper or lower respiratory infection, pulmonary exacerbation (PEx),
or change in therapy (including antibiotics) for sinopulmonary disease within
28 days before the first dose of study drug in the Run-in Period (Day -28).
4. Lung infection with a microbial pathogen that is associated with a more
rapid decline in pulmonary status (including, but not limited to, Burkholderia
cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus). For subjects
who have had a history of a positive culture, the investigator will apply the
following criteria to establish whether the subject is free of infection with
such organisms:
- The subject has not had respiratory tract culture positive for these
organisms within the 12 months before the date of informed consent.
- The subject has had at least 2 respiratory tract cultures negative for such
organisms within the 12 months before the date of informed consent, with the
first and last of these separated by at least 3 months, and the most recent one
within the 6 months before the date of informed consent.
5. An acute illness not related to CF (e.g., gastroenteritis) within 14 days
before the first dose of study drug in the Run-in Period (Day -28).
6. Ongoing or prior participation in a study of an investigational treatment
other than a Vertex CFTR modulator within 28 days or 5 terminal half-lives
(whichever is longer) before screening. The duration of the elapsed time may be
longer if required by local regulations.
7. Use of prohibited medications as defined in the protocol within the
specified window before the first dose of study drug in the Run-in Period (Day
-28).
8. Pregnant or breast-feeding females. All female subjects, regardless of
childbearing potential status, must have negative pregnancy tests at the
Screening Visit (Day -56) and at the Day -28 Visit, before the first dose of
study drug in the Run-in Period.
9. The subject or a close relative of the subject is the investigator or a
subinvestigator, research assistant, pharmacist, study coordinator, or other
staff directly involved with
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint<br /><br>- Absolute change in percent predicted forced expiratory volume in 1 second<br /><br>(ppFEV1) from baseline through Week 8 for the VX-445/TEZ/IVA group</p><br>
- Secondary Outcome Measures
Name Time Method <p>Key Secondary Endpoints<br /><br>- Absolute change in sweat chloride (SwCl) from baseline through Week 8 for the<br /><br>VX-445/TEZ/IVA group<br /><br>- Absolute change in ppFEV1 from baseline through Week 8 for the VX-445/TEZ/IVA<br /><br>group compared to the control group<br /><br>- Absolute change in SwCl from baseline through Week 8 for the VX-445/TEZ/IVA<br /><br>group compared to the control group<br /><br><br /><br>Other Secondary Endpoints<br /><br>- Absolute change in CF Questionnaire-Revised (CFQ-R) respiratory domain (RD)<br /><br>score from baseline through Week 8 for the VX-445/TEZ/IVA group<br /><br>- Absolute change in CFQ-R RD score from baseline through Week 8 for the<br /><br>VX-445/TEZ/IVA group compared to the control group<br /><br>- Safety and tolerability assessments based on adverse events (AEs), clinical<br /><br>laboratory values, ECGs, vital signs, and pulse oximetry</p><br>