Evaluation of the Efficacy and Safety of VX-864 in Subjec... | NCT04474197

ID	Type	Description	Link
2019-004881-16	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Participants received placebo matched to VX-864 in the treatment period for 28 days.	Drug: Placebo
VX-864 100 mg	Experimental	Participants received VX-864 100 milligrams (mg) every 12 hours (q12h) in the treatment period for 28 days.	Drug: VX-864
VX-864 300 mg	Experimental	Participants received VX-864 300 mg q12h in the treatment period for 28 days.	Drug: VX-864
VX-864 500 mg	Experimental	Participants received VX-864 500 mg q12h in the treatment period for 28 days.	Drug: VX-864

Name	Type	Description	Arm Group Labels	Other Names
VX-864	Drug	Tablets for oral administration.	VX-864 100 mg VX-864 300 mg VX-864 500 mg

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 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 (Ctrough) of VX-864		Pre-dose at Day 7, Day 14, Day 21 and Day 28

Eligibility Module

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35233	United States
David Geffen School of Medicine at UCLA

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants received placebo matched to VX-864 in the treatment period for 28 days.
FG001	VX-864 100 mg	Participants received VX-864 100 milligrams (mg) every 12 hours (q12h) in the treatment period for 28 days.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 12, 2021	May 2, 2022

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00063.4± 10.5 BG00155.1± 5.3 BG00253.2± 16.2 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0005 BG0016 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Plasma Functional Alpha-1 Antitrypsin (AAT) Levels

Mean

Standard Deviation

micromole per liter

Title

Denominators

Categories

Title	Measurements
	BG0004.7± 1.3 BG0014.0± 0.7 BG002

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.

Posted

Least Squares Mean

Standard Error

micromole per liter

From Baseline at Day 28

ID	Title	Description
OG000	Placebo	Participants received placebo matched to VX-864 in the treatment period for 28 days.
OG001	VX-864 100 mg	Participants received VX-864 100 mg q12h in the treatment period for 28 days.
OG002	VX-864 300 mg	Participants received VX-864 300 mg dose q12h in the treatment period for 28 days.
OG003	VX-864 500 mg	Participants received VX-864 500 mg dose q12h in the treatment period for 28 days.

Units	Counts
Participants	OG0007 OG00110 OG0029 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.1± 0.3 OG0012.3± 0.3 OG0022.3± 0.2 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed-effects Model for Repeated Measure		<0.0001		Least Squares (LS) Mean Difference	2.3			2-Sided	95	1.5	3.1					Superiority
OG000 OG002		Mixed-effects Model for Repeated Measure		<0.0001

Primary

Safety and Tolerability as Assessed by Number of Participants With 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

ID	Title	Description
OG000	Placebo	Participants received placebo matched to VX-864 in the treatment period for 28 days.
OG001	VX-864 100 mg	Participants received VX-864 100 mg q12h in the treatment period for 28 days.
OG002	VX-864 300 mg	Participants received VX-864 300 mg q12h in the treatment period for 28 days.
OG003	VX-864 500 mg	Participants received VX-864 500 mg q12h in the treatment period for 28 days.

Units	Counts

Secondary

Change in Plasma Antigenic AAT Levels

FAS.

Posted

Least Squares Mean

Standard Error

micromole per liter

From Baseline at Day 28

ID	Title	Description
OG000	Placebo	Participants received placebo matched to VX-864 in the treatment period for 28 days.
OG001	VX-864 100 mg	Participants received VX-864 100 mg q12h in the treatment period for 28 days.
OG002	VX-864 300 mg	Participants received VX-864 300 mg q12h in the treatment period for 28 days.
OG003	VX-864 500 mg	Participants received VX-864 500 mg q12h in the treatment period for 28 days.

Units	Counts
Participants

Secondary

Observed Pre-dose Plasma Concentration (Ctrough) of VX-864

Pharmacokinetic (PK) set included participants who received at least 1 dose of study drug. Here "Number analyzed" signifies those participants who were evaluable for this endpoint at specified time points.

Posted

Mean

Standard Deviation

microgram per milliliter

Pre-dose at Day 7, Day 14, Day 21 and Day 28

ID	Title	Description
OG000	VX-864 100 mg	Participants received VX-864 100 mg q12h in the treatment period for 28 days.
OG001	VX-864 300 mg	Participants received VX-864 300 mg q12h in the treatment period for 28 days.
OG002	VX-864 500 mg	Participants received VX-864 500 mg q12h in the treatment period for 28 days.

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG0031 affected18 at risk
Eye allergy	Eye disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Macular degeneration	Eye disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected10 at risk EG0020 affected9 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected10 at risk EG0021 affected9 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected10 at risk EG0021 affected9 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Gingival pain	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0022 affected9 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected10 at risk EG0020 affected9 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Asthenia	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Chills	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Fatigue	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0012 affected10 at risk EG0020 affected9 at risk EG003
Feeling abnormal	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected10 at risk EG0020 affected9 at risk EG003
Feeling cold	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected10 at risk EG0020 affected9 at risk EG003
Malaise	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Pyrexia	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0012 affected10 at risk EG0021 affected9 at risk EG003
Infective exacerbation of bronchiectasis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Skin infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected7 at risk EG0011 affected10 at risk EG0020 affected9 at risk EG003
Back injury	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Muscle strain	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Post procedural contusion	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Skin laceration	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Vaccination complication	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected10 at risk EG0020 affected9 at risk EG003
Blood bicarbonate decreased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Blood cholesterol increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Blood potassium decreased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Blood pressure diastolic increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Blood triglycerides increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Haemoglobin increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected10 at risk EG0020 affected9 at risk EG003
Low density lipoprotein increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Oxygen saturation decreased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected10 at risk EG0020 affected9 at risk EG003
Protein total decreased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Red blood cell count increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
White blood cells urine positive	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Carpal tunnel syndrome	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Dizziness	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected7 at risk EG0011 affected10 at risk EG0022 affected9 at risk EG003
Dysaesthesia	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Headache	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected10 at risk EG0022 affected9 at risk EG003
Tremor	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Poor quality sleep	Psychiatric disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Heavy menstrual bleeding	Reproductive system and breast disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected10 at risk EG0020 affected9 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0012 affected10 at risk EG0020 affected9 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected10 at risk EG0020 affected9 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected10 at risk EG0020 affected9 at risk EG003
Respiration abnormal	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected10 at risk EG0020 affected9 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0021 affected9 at risk EG003
Sneezing	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Sputum increased	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected10 at risk EG0020 affected9 at risk EG003
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected10 at risk EG0020 affected9 at risk EG003
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Polymorphic light eruption	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected10 at risk EG0020 affected9 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003

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

ID	Title	Description
BG000	Placebo	Participants received placebo matched to VX-864 in the treatment period for 28 days.
BG001	VX-864 100 mg	Participants received VX-864 100 mg q12h in the treatment period for 28 days.
BG002	VX-864 300 mg	Participants received VX-864 300 mg q12h in the treatment period for 28 days.
BG003	VX-864 500 mg	Participants received VX-864 500 mg q12h in the treatment period for 28 days.
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received placebo matched to VX-864 in the treatment period for 28 days.	7	0	7	4	7
EG001	VX-864 100 mg	Participants received VX-864 100 mg q12h in the treatment period for 28 days.	10	0	10	7	10
EG002	VX-864 300 mg	Participants received VX-864 300 mg q12h in the treatment period for 28 days.	9	0	9	7	9
EG003	VX-864 500 mg	Participants received VX-864 500 mg q12h in the treatment period for 28 days.	18	2	18	17	18

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Chest pain	General disorders	Meddra 24.0	Systematic Assessment		EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG0031 affected18 at risk
Pneumothorax spontaneous	Respiratory, thoracic and mediastinal disorders	Meddra 24.0	Systematic Assessment		EG0000 affected7 at risk EG0010 affected10 at risk EG0020 affected9 at risk EG003