A Phase 2 Study to Evaluate Efficacy and Safety of VX-561... | NCT03911713

NCT03911713

ID	Type	Description	Link
2018-003970-28	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Ivacaftor	Active Comparator	Participants received IVA 150 milligrams (mg) orally every 12 hours (q12h) in the treatment period for 12 weeks.	Drug: IVA Drug: Placebo
VX-561: 25 mg	Experimental	Participants received VX-561 25 mg orally daily (qd) in the treatment period for 12 weeks.	Drug: VX-561 Drug: Placebo
VX-561: 50 mg	Experimental	Participants received VX-561 50 mg orally qd in the treatment period for 12 weeks.	Drug: VX-561 Drug: Placebo
VX-561: 150 mg	Experimental	Participants received VX-561 150 mg orally qd in the treatment period for 12 weeks.	Drug: VX-561 Drug: Placebo
VX-561: 250 mg	Experimental	Participants received VX-561 250 mg orally qd in the treatment period for 12 weeks.	Drug: VX-561 Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
VX-561	Drug	VX-561 tablets for oral administration.	VX-561: 150 mg VX-561: 25 mg VX-561: 250 mg VX-561: 50 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	From Baseline at Week 12

Secondary Outcomes

Measure	Description	Time Frame
Absolute Change in Sweat Chloride (SwCl)	Sweat samples were collected using an approved collection device.	From Baseline at Week 12
Observed Pre-Dose Concentration (Ctrough) of VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) and IVA and Its Metabolites (M1-IVA and M6-IVA)

Eligibility Module

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35233	United States
Banner University of Arizona Medical Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
36842446	Derived	Uluer AZ, MacGregor G, Azevedo P, Indihar V, Keating C, Mall MA, McKone EF, Ramsey BW, Rowe SM, Rubenstein RC, Taylor-Cousar JL, Tullis E, Yonker LM, Chu C, Lam AP, Nair N, Sosnay PR, Tian S, Van Goor F, Viswanathan L, Waltz D, Wang LT, Xi Y, Billings J, Horsley A; VX18-121-101; VX18-561-101 Study Groups. Safety and efficacy of vanzacaftor-tezacaftor-deutivacaftor in adults with cystic fibrosis: randomised, double-blind, controlled, phase 2 trials. Lancet Respir Med. 2023 Jun;11(6):550-562. doi: 10.1016/S2213-2600(22)00504-5. Epub 2023 Feb 23.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Ivacaftor	Participants received IVA 150 milligrams (mg) orally every 12 hours (q12h) in the treatment period for 12 weeks.
FG001	VX-561: 25 mg	Participants received VX-561 25 mg orally once daily (qd) in the treatment period for 12 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 3, 2019	Nov 9, 2021

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

CTP-656
Deutivacaftor (D-IVA)

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Ivacaftor	Participants received IVA 150 mg orally q12h in the treatment period for 12 weeks.
BG001	VX-561: 25 mg	Participants received VX-561 25 mg orally qd in the treatment period for 12 weeks.
BG002	VX-561: 50 mg	Participants received VX-561 50 mg orally qd in the treatment period for 12 weeks.
BG003	VX-561: 150 mg	Participants received VX-561 150 mg orally qd in the treatment period for 12 weeks.
BG004	VX-561: 250 mg	Participants received VX-561 250 mg orally qd in the treatment period for 12 weeks.
BG005	Total	Total of all reporting groups

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
	BG00033.3± 11.7 BG00133.0± 10.6 BG00227.8± 9.0 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0004 BG0012 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

Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Mean

Standard Deviation

percentage points

Title

Denominators

Categories

Title	Measurements
	BG00074.0± 21.2 BG001

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

Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Full analysis set (FAS) included all randomized participants who have intended CF transmembrane conductance regulator gene (CFTR) genotype and received at least 1 dose of study drug in treatment period. VX-561:25 mg and VX-561:50 mg arms were discontinued at sponsor's discretion and it was specified in statistical plan that data will be reported for only IVA, VX-561:150 mg and VX-561:250 mg arms for this outcome measure.

Posted

Least Squares Mean

95% Confidence Interval

percentage points

From Baseline at Week 12

ID	Title	Description
OG000	Ivacaftor	Participants received IVA 150 mg orally q12h in the treatment period for 12 weeks.
OG001	VX-561: 150 mg	Participants received VX-561 150 mg orally qd in the treatment period for 12 weeks.
OG002	VX-561: 250 mg	Participants received VX-561 250 mg orally qd in the treatment period for 12 weeks.

Units	Counts
Participants	OG00011 OG00123 OG00224

Title

Denominators

Categories

Title	Measurements
	OG000-0.8(-6.2 to 4.7) OG0013.1(-0.8 to 7.0) OG0022.7(-1.0 to 6.5)

Secondary

Absolute Change in Sweat Chloride (SwCl)

Sweat samples were collected using an approved collection device.

FAS. VX-561:25 mg and VX-561:50 mg arms were discontinued at sponsor's discretion and it was specified in statistical plan that data will be reported for only IVA, VX-561:150 mg and VX-561:250 mg arms for this outcome measure.

Posted

Least Squares Mean

95% Confidence Interval

millimole per liter (mmol/L)

From Baseline at Week 12

ID	Title	Description
OG000	Ivacaftor	Participants received IVA 150 mg orally q12h in the treatment period for 12 weeks.
OG001	VX-561: 150 mg	Participants received VX-561 150 mg orally qd in the treatment period for 12 weeks.
OG002	VX-561: 250 mg	Participants received VX-561 250 mg orally qd in the treatment period for 12 weeks.

Units	Counts
Participants

Secondary

Observed Pre-Dose Concentration (Ctrough) of VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) and IVA and Its Metabolites (M1-IVA and M6-IVA)

Pharmacokinetic (PK) set included all participants who received at least 1 dose of study drug and for whom the primary PK data were considered to be sufficient and interpretable. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those who were evaluable for the specific category.

Posted

Mean

Standard Deviation

nanogram per milliliter (ng/mL)

At Week 4

ID	Title	Description
OG000	Ivacaftor	Participants received IVA 150 mg orally q12h in the treatment period for 12 weeks.
OG001	VX-561: 25 mg	Participants received VX-561 25 mg orally qd in the treatment period for 12 weeks.
OG002	VX-561: 50 mg	Participants received VX-561 50 mg orally qd in the treatment period for 12 weeks.
OG003	VX-561: 150 mg	Participants received VX-561 150 mg orally qd in the treatment period for 12 weeks.

Secondary

Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Safety Set included all participants who received at least 1 dose of study drug.

Posted

Number

participants

Baseline up to Week 16

ID	Title	Description
OG000	Ivacaftor	Participants received IVA 150 mg orally q12h in the treatment period for 12 weeks.
OG001	VX-561: 25 mg	Participants received VX-561 25 mg orally qd in the treatment period for 12 weeks.
OG002	VX-561: 50 mg	Participants received VX-561 50 mg orally qd in the treatment period for 12 weeks.
OG003	VX-561: 150 mg	Participants received VX-561 150 mg orally qd in the treatment period for 12 weeks.
OG004	VX-561: 250 mg

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ivacaftor	Participants received IVA 150 mg orally q12h in the treatment period for 12 weeks.	11	1	11	8	11
EG001	VX-561: 25 mg	Participants received VX-561 25 mg orally qd in the treatment period for 12 weeks.	6	2	6	4	6
EG002	VX-561: 50 mg	Participants received VX-561 50 mg orally qd in the treatment period for 12 weeks.	11	2	11	8	11
EG003	VX-561: 150 mg	Participants received VX-561 150 mg orally qd in the treatment period for 12 weeks.	23	2	23	17	23
EG004	VX-561: 250 mg	Participants received VX-561 250 mg orally qd in the treatment period for 12 weeks.	24	1	24	20	24

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Distal intestinal obstruction syndrome	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0020 affected11 at risk EG0030 affected23 at risk EG004
Infective pulmonary exacerbation of cystic fibrosis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0011 affected6 at risk EG0022 affected11 at risk EG003
Forced expiratory volume decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0020 affected11 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Leukocytosis	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0020 affected11 at risk EG0030 affected23 at risk EG0040 affected24 at risk
Palpitations	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0020 affected11 at risk EG003
Glaucoma	Eye disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0020 affected11 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0021 affected11 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0011 affected6 at risk EG0020 affected11 at risk EG003
Duodenitis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0020 affected11 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0011 affected6 at risk EG0021 affected11 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0020 affected11 at risk EG003
Chest discomfort	General disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Fatigue	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0020 affected11 at risk EG003
Malaise	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0020 affected11 at risk EG003
Pyrexia	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0020 affected11 at risk EG003
Bronchopulmonary aspergillosis allergic	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected6 at risk EG0021 affected11 at risk EG003
Epididymitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected6 at risk EG0021 affected11 at risk EG003
Fungal skin infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0020 affected11 at risk EG003
Infective pulmonary exacerbation of cystic fibrosis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0002 affected11 at risk EG0010 affected6 at risk EG0022 affected11 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0002 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0011 affected6 at risk EG0020 affected11 at risk EG003
Sinusitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0020 affected11 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0021 affected11 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0022 affected11 at risk EG003
Atypical mycobacterium test positive	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected6 at risk EG0021 affected11 at risk EG003
Bacterial test positive	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0022 affected11 at risk EG003
Blood glucose increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Coronavirus test positive	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Forced expiratory volume decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0021 affected11 at risk EG003
Protein urine present	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Pulmonary function test decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected6 at risk EG0021 affected11 at risk EG003
Urine ketone body present	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Weight decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0020 affected11 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0020 affected11 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0020 affected11 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected6 at risk EG0021 affected11 at risk EG003
Dizziness	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Headache	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Migraine	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Sinus headache	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected11 at risk EG0011 affected6 at risk EG0021 affected11 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0012 affected6 at risk EG0020 affected11 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Increased viscosity of bronchial secretion	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected6 at risk EG0021 affected11 at risk EG003
Lower respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected11 at risk EG0011 affected6 at risk EG0021 affected11 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Paranasal sinus discomfort	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected6 at risk EG0021 affected11 at risk EG003
Pulmonary pain	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003
Rales	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0011 affected6 at risk EG0021 affected11 at risk EG003
Respiration abnormal	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected11 at risk EG0010 affected6 at risk EG0021 affected11 at risk EG003
Sputum increased	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected6 at risk EG0021 affected11 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected6 at risk EG0021 affected11 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected11 at risk EG0010 affected6 at risk EG0021 affected11 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected11 at risk EG0010 affected6 at risk EG0020 affected11 at risk EG003

First MCP Posted Date

ID	Term
D003550	Cystic Fibrosis

Ancestor Terms

ID	Term
D010182	Pancreatic Diseases
D004066	Digestive System Diseases
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D007232	Infant, Newborn, Diseases

ID	Term
C545203	ivacaftor

Participants received VX-561 250 mg orally qd in the treatment period for 12 weeks.

EG0041 affected24 at risk

EG0040 affected24 at risk

EG0041 affected24 at risk

EG0040 affected24 at risk

EG0044 affected24 at risk

EG0043 affected24 at risk

EG0041 affected24 at risk

EG0042 affected24 at risk

EG0040 affected24 at risk

EG0041 affected24 at risk

EG0040 affected24 at risk

EG0041 affected24 at risk

EG0040 affected24 at risk

EG0041 affected24 at risk

EG0040 affected24 at risk

EG0041 affected24 at risk

EG0040 affected24 at risk

EG0041 affected24 at risk

EG0040 affected24 at risk

EG0041 affected24 at risk

EG0040 affected24 at risk

EG0041 affected24 at risk

EG0040 affected24 at risk

EG0041 affected24 at risk

EG0040 affected24 at risk

EG0041 affected24 at risk

EG0040 affected24 at risk

EG0043 affected24 at risk

EG0040 affected24 at risk

EG0042 affected24 at risk