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at Sponsor's discretion
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This study will evaluate the efficacy, safety and pharmacokinetics (PK) of VX-814 in PiZZ subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Parts A1, A2 and B Combined: Placebo | Placebo Comparator | Participants received placebo matched to VX-814 in the treatment period for 28 days. |
|
| Part A1: VX-814 100 milligrams (mg) | Experimental | Participants received VX-814 100 mg every 12 hours (q12h) in the treatment period for 28 days. |
|
| Part A1: VX-814 200 mg | Experimental | Participants received VX-814 200 mg q12h in the treatment period for 28 days. |
|
| Parts A1 and A2 Combined: VX-814 400 mg | Experimental | Participants received VX-814 400 mg q12h in the treatment period for 28 days. |
|
| Part B: VX-814 600 mg | Experimental | Participants received VX-814 600 mg q12h in the treatment period for 28 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VX-814 | Drug | Tablet for oral administration. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Plasma Functional Alpha-1 Antitrypsin (AAT) Levels | From Baseline at Day 28 | |
| Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to Week 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Plasma Antigenic AAT Levels | From Baseline at Day 28 | |
| Observed Pre-dose Plasma Concentration of VX-814 | Pre-dose at Day 7, Day 14, Day 21, and Day 28 |
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Key Inclusion Criteria:
Key Exclusion Criteria:
Other protocol defined Inclusion/Exclusion criteria may apply
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35233 | United States | ||
| University of California Davis Medical Center |
Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing
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This study was conducted in participants 18 through 80 of years of age, inclusive with the PiZZ genotype.
There were 3 parts in the study: Parts A1, A2 and B. As pre-specified in SAP, data collected for the placebo group for Parts A1, A2 and B were pooled and reported as a single combined arm (Parts A1, A2 and B Combined: Placebo) and data collected for VX-814 400 mg for Parts A1 and A2 were pooled and reported as a single combined arm (Parts A1 and A2 Combined: VX-814 400 milligrams [mg]) in the below presented results.
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| ID | Title | Description |
|---|---|---|
| FG000 | Parts A1, A2 and B Combined: Placebo | Participants received placebo matched to VX-814 in the treatment period for 28 days. |
| FG001 | Part A1: VX-814 100 mg | Participants received VX-814 100 mg once every 12 hours (q12h) in the treatment period for 28 days. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 21, 2020 | Nov 11, 2021 |
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| Placebo | Drug | Placebo matched to VX-814 for oral administration. |
|
| Sacramento |
| California |
| 95817 |
| United States |
| National Jewish Health | Denver | Colorado | 80206 | United States |
| University of Florida, Shands Hospital | Gainesville | Florida | 32610 | United States |
| University of Miami Miller School of Medicine | Miami | Florida | 33136 | United States |
| Central Florida Pulmonary Group, PA | Orlando | Florida | 32803 | United States |
| The University of Iowa Hospitals and Clinics | Iowa City | Iowa | 52242 | United States |
| University of Kansas Medical Center | Kansas City | Kansas | 66160 | United States |
| University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| Blessing Corporate Services, Inc., dba Blessing Health System | Hannibal | Missouri | 63401 | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| University of North Carolina Medical Center | Chapel Hill | North Carolina | 27514 | United States |
| Wake Forest University Baptist Medical Center | Winston-Salem | North Carolina | 27157 | United States |
| University of Cincinnati | Cincinnati | Ohio | 45267 | United States |
| Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States |
| Oregon Health & Science University | Portland | Oregon | 97239 | United States |
| Temple University Hospital | Philadelphia | Pennsylvania | 19140 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| Renovatio Clinical | Houston | Texas | 77380 | United States |
| The University of Texas Health Science Center at Tyler | Tyler | Texas | 75708 | United States |
| University of Utah Health | Salt Lake City | Utah | 84108 | United States |
| Inova Fairfax Medical Campus | Falls Church | Virginia | 22042 | United States |
| Queen Elizabeth II Health Sciences Center | Halifax | Canada |
| Inspiration Research Ltd | Toronto | Canada |
| University Hospital RWTH Aachen | Aachen | Germany |
| Universitätsklinikum Essen | Essen | Germany |
| Medizinische Hochschule Hannover | Hanover | Germany |
| Royal College of Surgeons in Ireland Clinical Research Centre, Beaumont Hospital | Beaumont | Ireland |
| FG002 | Part A1: VX-814 200 mg | Participants received VX-814 200 mg q12h in the treatment period for 28 days. |
| FG003 | Parts A1 and A2 Combined: VX-814 400 mg | Participants received VX-814 400 mg q12h in the treatment period for 28 days. |
| FG004 | Part B: VX-814 600 mg | Participants received VX-814 600 mg q12h in the treatment period for 28 days. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Parts A1, A2 and B Combined: Placebo | Participants received placebo matched to VX-814 in the treatment period for 28 days. |
| BG001 | Part A1: VX-814 100 mg | Participants received VX-814 100 mg q12h in the treatment period for 28 days. |
| BG002 | Part A1: VX-814 200 mg | Participants received VX-814 200 mg q12h in the treatment period for 28 days. |
| BG003 | Parts A1 and A2 Combined: VX-814 400 mg | Participants received VX-814 400 mg q12h in the treatment period for 28 days. |
| BG004 | Part B: VX-814 600 mg | Participants received VX-814 600 mg q12h in the treatment period for 28 days. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Plasma Functional Alpha-1 Antitrypsin (AAT) Levels | Mean | Standard Deviation | micromole per liter |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Plasma Functional Alpha-1 Antitrypsin (AAT) Levels | Full analysis set (FAS) included all randomized participants who received at least 1 dose of study drug. The "overall number of participants analyzed" signifies participants who were evaluable at the specified time point. As pre-specified in SAP, statistical comparison with placebo were planned only for VX-814 400 mg and 600 mg treatment arms. | Posted | Mean | Standard Deviation | micromole per liter | From Baseline at Day 28 |
|
|
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| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | The safety set included all participants who received at least 1 dose of study drug. | Posted | Number | participants | Day 1 up to Week 8 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Plasma Antigenic AAT Levels | FAS. The "overall number of participants analyzed" signifies participants who were evaluable at the specified time point. As pre-specified in SAP, statistical comparisons with placebo were planned only for VX-814 400 mg and 600 mg treatment arms. | Posted | Mean | Standard Deviation | micromole per liter | From Baseline at Day 28 |
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| Secondary | Observed Pre-dose Plasma Concentration of VX-814 | Pharmacokinetic analysis included all randomized participants who received at least 1 dose of study drug. Here "number analyzed" signifies participants who were evaluable at the specified time point. | Posted | Mean | Standard Deviation | microgram per milliliter | Pre-dose at Day 7, Day 14, Day 21, and Day 28 |
|
Day 1 up to Week 8
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Parts A1, A2 and B Combined: Placebo | Participants received placebo matched to VX-814 in the treatment period for 28 days. | 0 | 10 | 0 | 10 | 4 | 10 |
| EG001 | Part A1: VX-814 100 mg | Participants received VX-814 100 mg q12h in the treatment period for 28 days. | 0 | 4 | 2 | 4 | 1 | 4 |
| EG002 | Part A1: VX-814 200 mg | Participants received VX-814 200 mg q12h in the treatment period for 28 days. | 0 | 3 | 1 | 3 | 0 | 3 |
| EG003 | Parts A1 and A2 Combined: VX-814 400 mg | Participants received VX-814 400 mg q12h in the treatment period for 28 days. | 0 | 13 | 1 | 13 | 9 | 13 |
| EG004 | Part B: VX-814 600 mg | Participants received VX-814 600 mg q12h in the treatment period for 28 days. | 0 | 18 | 0 | 18 | 14 | 18 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Frequent bowel movements | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Ear infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Tooth abscess | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Vulvovaginal candidiasis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Dental restoration failure | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Blood cholesterol increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Blood pressure increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Crystal urine present | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Eosinophil count increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Protein urine present | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Prothrombin time prolonged | Investigations | MedDRA 23.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Restless legs syndrome | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Nightmare | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
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| Pollakiuria | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
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| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Respiration abnormal | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Hot flush | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
|
During the study, elevated liver enzymes (AST/ALT) were observed in several participants and analysis of available pharmacokinetics data indicated that VX-814 exposures achieved were low. Based on these data, Vertex concluded that it would not be feasible to safely reach targeted exposure levels with VX-814. Thus, the study was terminated early at the sponsor's discretion. Given the study was terminated early, the data are incomplete, and results should be interpreted with caution.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Monitor | Vertex Pharmaceuticals Incorporated | 617-341-6777 | medicalinfo@vrtx.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 11, 2020 | Nov 11, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D019896 | alpha 1-Antitrypsin Deficiency |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D013352 | Subcutaneous Emphysema |
| D004646 | Emphysema |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Mean Difference |
| 2.0 |
| 2-Sided |
| 95 |
| 1.1 |
| 2.9 |
| Superiority |
Participants received VX-814 600 mg q12h in the treatment period for 28 days. |
|
|
| Part B: VX-814 600 mg |
Participants received VX-814 600 mg q12h in the treatment period for 28 days. |
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
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| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|