Alpha-1 Antitrypsin Deficiency
Conditions
Brief summary
The purpose of this study evaluates the efficacy and safety of VX-864 in participants with the PiZZ genotype over 48 weeks.
Interventions
DRUGVX-864
Tablets for oral administration.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participants must have a PiZZ genotype confirmed at screening * Plasma AAT levels indicating severe deficiency at screening Key
Exclusion criteria
* History of a medical condition that could negatively impact the ability to complete the study * Solid organ, or hematological transplantation or is currently on a transplant list * History of use of gene therapy or Ribonucleic acid interference (RNAi) therapy at any time previously * Participants for whom discontinuation of augmentation therapy is not considered to be in their best interest, based on the clinical judgement of the treating physician Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Blood Functional Alpha-1 Antitrypsin (AAT) Levels | From Baseline at Week 48 |
Secondary
| Measure | Time frame |
|---|---|
| Change in Blood Functional AAT Levels | From Baseline up to Week 48 |
| Change in Blood Antigenic AAT Levels | From Baseline up to Week 48 |
| Change in Blood Z-polymer Levels | From Baseline up to Week 48 |
| Group B: Change in Z-polymer Accumulation in the Liver | From Baseline up to Week 48 |
| Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to Week 52 |
Countries
Germany, Ireland, United Kingdom, United States
Participant flow
Recruitment details
This study had 2 Groups: Group A participants did not have a liver biopsy and Group B participants have 2 liver biopsies performed over the course of the study.
Pre-assignment details
A total of 14 participants were enrolled from 23 February 2023 to 03 November 2023 in this study. Study drug dosing and efficacy assessments were terminated early due to Sponsor decision, therefore evaluation of efficacy outcome measure was not completed.
Participants by arm
| Arm | Count |
|---|---|
| Group A VX-864 500 mg Participants received VX-864 q12h for 48 weeks or until study drug dosing was terminated. | 10 |
| Group B VX-864 500 mg Participants undergo a liver biopsy before receiving VX-864 q12h for 48 weeks or until study drug dosing was terminated and undergo a second liver biopsy at either Week 24 or Week 48. | 4 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Withdrawal of consent (not due to AE) | 1 | 1 |
Baseline characteristics
| Characteristic | Group A VX-864 500 mg | Group B VX-864 500 mg | Total |
|---|---|---|---|
| Age, Continuous | 52.8 years STANDARD_DEVIATION 14.2 | 50.8 years STANDARD_DEVIATION 10.4 | 52.2 years STANDARD_DEVIATION 12.9 |
| Race/Ethnicity, Customized Not Hispanic or Latino | 10 Participants | 4 Participants | 14 Participants |
| Race/Ethnicity, Customized White | 10 Participants | 4 Participants | 14 Participants |
| Sex: Female, Male Female | 8 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 4 |
| other Total, other adverse events | 10 / 10 | 4 / 4 |
| serious Total, serious adverse events | 1 / 10 | 0 / 4 |
Outcome results
Primary
Change in Blood Functional Alpha-1 Antitrypsin (AAT) Levels
Time frame: From Baseline at Week 48
Population: Data was not collected for this Outcome Measure as the study drug dosing was terminated prior to any participant reaching Week 48.
Secondary
Change in Blood Antigenic AAT Levels
Time frame: From Baseline up to Week 48
Population: Data was not collected for this Outcome Measure as the study drug dosing was terminated prior to any participant reaching Week 48.
Secondary
Change in Blood Functional AAT Levels
Time frame: From Baseline up to Week 48
Population: Data was not collected for this Outcome Measure as the study drug dosing was terminated prior to any participant reaching Week 48.
Secondary
Change in Blood Z-polymer Levels
Time frame: From Baseline up to Week 48
Population: Data was not collected for this Outcome Measure as the study drug dosing was terminated prior to any participant reaching Week 48.
Secondary
Group B: Change in Z-polymer Accumulation in the Liver
Time frame: From Baseline up to Week 48
Population: No participants in Group B underwent a second liver biopsy at week 24 or week 48 as the study drug dosing was terminated prior to any participant reaching week 24 or week 48. Therefore, data was not collected for this Outcome Measure.
Secondary
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Week 52
Population: Safety set included all participants who had received at least 1 dose of study drug in this study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A VX-864 500 mg | Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 10 Participants |
| Group A VX-864 500 mg | Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 1 Participants |
| Group B VX-864 500 mg | Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Group B VX-864 500 mg | Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 4 Participants |