Evaluation of the Efficacy and Safety of VX-814 in Subjects With the PiZZGenotype
- Conditions
- Alpha-1 Antitrypsin DeficiencyTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2019-003650-92-IE
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 43
1. Subject will sign and date an informed consent form (ICF).
2. Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
3. Subjects will be 18 through 80 years of age, inclusive, at the time of signing of the ICF.
4. All female subjects must have a negative pregnancy test at screening (serum test). Premenopausal female subjects of child-bearing potential must also have a negative pregnancy test on Day 1 (urine test) and must not be nursing or planning to become pregnant during the study or within 90 days after the last study drug dose.
5. Body mass index (BMI) of 18.0 to 35.0 kg/m2, inclusive.
6. Subjects must have a PiZZ genotype confirmed at screening.
NOTE: PiZZ genotype must be tested at the central laboratory. Historical genotype results can be used to determine eligibility if they were obtained as part of a different Vertex study. In addition, if the screening PiZZ genotype result is not received before randomization, a previous non-Vertex PiZZ genotype laboratory report (approved by the medical monitor or designee) may be used to establish provisional eligibility. Subjects who have been randomized and whose screening genotype subsequently does not confirm study eligibility must be discontinued from the study (Section 9.10).
7. Plasma antigenic AAT level <8 ìM during screening.
For subjects who have been on augmentation therapy at any time, results used to confirm eligibility must be drawn >42 days after the last dose of augmentation therapy. Antigenic AAT levels must be obtained from the central laboratory and results confirmed before randomization.
8. Willing to remain off of augmentation therapy from >42 days before antigenic AAT levels are obtained for eligibility through the last Safety Follow-Up Visit
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 26
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 17
1. History or presence of any illness or clinical condition that, in the opinion of the investigator, might affect the subject's safety or compliance or 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:
• Solid organ, lung, or hematological transplantation or is currently on a transplant list
• Subjects who have undergone gastrectomy or other gastrointestinal tract surgery, except appendectomy, cholecystectomy, and hemorrhoid surgery
• Cancer, except for squamous cell skin cancer, basal cell skin cancer, Stage 0 cervical carcinoma in situ, and stage 0 or 1 melanoma(all 4 with no recurrence during the last 5 years)
2. History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year before screening, defined as more than 14 drinks/week for females or 21 drinks/week for males (1 drink=5 ounces(150 mL)of wine or 12 ounces(360 mL)of beer or 1.5 ounces (45 mL) of hard liquor)
3. Illegal drug use within 1 year before screening as deemed by the investigator, including but not limited to cocaine, heroin, and other opioids
4. Ongoing or prior participation in a study of an investigational treatment 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
5. History of use of gene therapy or RNAi therapy at any time previously
6. Use of oral corticosteroids(at any dose)for a duration of greater than 3 months at any time within the 3 months before screening
7. A post-bronchodilator forced expiratory volume in 1 second(FEV1) value<30% of predicted mean for age, sex, and height (equations of the Global Lung Function Initiative[GLI])during screening. Post-bronchodilator spirometry measurements must meet American Thoracic Society(ATS)/European Respiratory Society(ERS)criteria for acceptability and repeatability
8. All clinically important pulmonary disease other than AATD-related COPD, including but not limited to physician-diagnosed COPD not related to AATD, interstitial lung disease, cystic fibrosis, pulmonary hypertension with or without cor pulmonale, history of pulmonary embolism, or malignant lung cancer
9. Unstable AATD-related COPD as deemed by the investigator
10. Documented chronic need for positive airway pressure therapy beyond nocturnal use
11. Documented medical history or diagnosis of clinically evident liver disease including but not limited to a prior diagnosis of hepatitis of any etiology, cirrhosis, portal hypertension, or confirmed or suspected esophageal varices
12. Any of the following abnormal laboratory values at screening:
. Platelet count <150 ~ 109/L
. Albumin .3.5 g/dL
. International normalized ratio .1.2
. Hemoglobin <10 g/dL
. Total bilirubin > upper limit of normal (ULN)
. Aspartate transaminase(AST), alanine transaminase(ALT), gamma-glutamyl transferase(GGT), or alkaline phosphatase(ALP)>2 ~ ULN
. Estimated glomerular filtration rate .30 mL/min/1.73 m2
13. Risk factors for Torsade de Pointes or concomitant medications that prolong the QT/QTc interval or any history of unstable cardiac disorder that, in the opinion of the investigator, might put the subject at risk or may confound the results of the study
14. Any clinically significant ECG abnormality (as determined by the investigator) or median QTcF of triplicate standard 12-lead ECGs >450 msec at screening
15. History
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method