Alpha 1 antitrypsin deficiency in Subjects With the PiZZ Genotype MedDRA version: 23.1 Level: PT Classification code 10083869 Term: Alpha-1 antitrypsin deficiency System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: VX864
Product Code: VX864
Pharmaceutical Form: Tablet
INN or Proposed INN: VX864
Current Sponsor code: VX-864
Other descriptive name: VX-864
Concentration unit: mg milligram(s)
Concentra
Sponsors
Vertex Pharmaceuticals Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 breastfeeding 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. 7. Plasma antigenic AAT level 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 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 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 basal cell skin cancer, Stage 0 cervical carcinoma in situ, and Stage 0 melanoma (regardless of recurrence), or adequately treated squamous cell skin cancer and Stage 1 melanoma (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 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. 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 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 (eGFR) .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 or median QTcF of triplicate standard 12-lead ECGs >450 msec at screening. 15. History of Gilbert's Syndrome. 16. Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) RNA, or HIV-1 and HI
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of VX-864 in PiZZ subjects as measured by plasma functional AAT levels • To evaluate the safety and tolerability of VX-864 in PiZZ subjects ;Secondary Objective: • To evaluate the efficacy of VX-864 in PiZZ subjects as measured by plasma antigenic AAT levels • To evaluate the pharmacokinetics (PK) of VX-864 in PiZZ subjects ;Primary end point(s): • Change from baseline in plasma functional AAT levels at Day 28 • Safety and tolerability assessments based on adverse events (AEs), clinical laboratory values, standard 12 lead ECGs, vital signs and pulse oximetry.;Timepoint(s) of evaluation of this end point: Plasma Functional AAT levels: From base line to day 28 Safety and tolerability assessment: From baseline to Safety follow up visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change from baseline in plasma antigenic AAT levels at Day 28 • PK parameters of VX-864 derived from plasma concentration time data ;Timepoint(s) of evaluation of this end point: change in AAT Levels: From baseline to Day 28 PK Parameters: From baseline to safety follow up visit | — |
Countries
Canada, Germany, Ireland, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Trials and Medical Info
Vertex Pharmaceuticals Incorporated
Outcome results
None listed