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The EU Clinical Trials Register currently displays 44334 clinical trials with a EudraCT protocol, of which 7366 are clinical trials conducted with subjects less than 18 years old. The register also displays information on 18700 older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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Clinical Trial Results:
A Phase 3 Double-blind, Randomized, Placebo-controlled Study Evaluating the Efficacy and Safety of ELX/TEZ/IVA in Cystic Fibrosis Subjects 6 Years of Age and Older With a Non-F508del ELX/TEZ/IVA-responsive CFTR Mutation

Summary
EudraCT number	2021-005320-38
Trial protocol	ES DE FR BE AT IT PT NL SE CZ NO HU PL
Global end of trial date	05 Jul 2023

Results information
Results version number	v1
This version publication date	18 Jan 2024
First version publication date	18 Jan 2024
Other versions	v2

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

VX21-445-124

ISRCTN number

-

US NCT number

NCT05274269

WHO universal trial number (UTN)

-

Sponsor organisation name

Vertex Pharmaceuticals Incorporated

Sponsor organisation address

50 Northern Avenue , Boston, Massachusetts, United States,

Public contact

Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617-341-6777, medicalinfo@vrtx.com

Scientific contact

Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617-341-6777, medicalinfo@vrtx.com

Is trial part of an agreed paediatric investigation plan (PIP)

No

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

25 Jul 2023

Is this the analysis of the primary completion data?

Yes

Primary completion date

05 Jul 2023

Global end of trial reached?

Yes

Global end of trial date

05 Jul 2023

Was the trial ended prematurely?

No

Main objective of the trial

To evaluate the efficacy and pharmacodynamics (PD) of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA).

Protection of trial subjects

The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki and the International Conference on Harmonization (ICH) Guideline for Good Clinical Practice (GCP).

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

09 May 2022

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 24

Country: Number of subjects enrolled

Switzerland: 4

Country: Number of subjects enrolled

Netherlands: 21

Country: Number of subjects enrolled

Norway: 2

Country: Number of subjects enrolled

Poland: 6

Country: Number of subjects enrolled

Portugal: 5

Country: Number of subjects enrolled

Spain: 52

Country: Number of subjects enrolled

Sweden: 4

Country: Number of subjects enrolled

Austria: 2

Country: Number of subjects enrolled

Belgium: 19

Country: Number of subjects enrolled

Czechia: 6

Country: Number of subjects enrolled

France: 41

Country: Number of subjects enrolled

Germany: 38

Country: Number of subjects enrolled

Hungary: 2

Country: Number of subjects enrolled

Italy: 81

Worldwide total number of subjects

307

EEA total number of subjects

279

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

32

Adolescents (12-17 years)

32

Adults (18-64 years)

237

From 65 to 84 years

5

85 years and over

1

Subject disposition

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Recruitment details

-

Screening details

This study was conducted in CF subjects aged 6 years and older with a non-F508del ELX/TEZ/IVA-responsive cystic fibrosis transmembrane conductance regulator gene (CFTR) mutation.

Period 1 title

Overall Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

ELX/TEZ/IVA

Arm description

Subjects 6 to less than (<) 12 year of age and weighing <30 kilogram (kg) at Day 1 received ELX 100 milligram (mg)/TEZ 50 mg /IVA 75 mg as fixed dose combination (FDC) tablets in the morning and IVA as mono tablet in the evening and those weighing more than or equal to (≥) 30 kg at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 24 weeks. Subjects ≥12 years age at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 24 weeks.

Arm type

Experimental

Investigational medicinal product name

ELX/TEZ/IVA

Investigational medicinal product code

VX-445/VX-661/VX-770

Other name

elexacaftor/tezacaftor/ivacaftor

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received ELX/TEZ/IVA FDC once daily in the morning.

Investigational medicinal product name

IVA

Investigational medicinal product code

VX-770

Other name

ivacaftor

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received IVA once daily in the evening.

Placebo

Arm description

Subjects received placebo matched to ELX/TEZ/IVA FDC in the morning and placebo matched to IVA in the evening for 24 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo (matched to ELX/TEZ/IVA)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received placebo matched to ELX/TEZ/IVA once daily in the morning.

Investigational medicinal product name

Placebo (matched to IVA)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received placebo matched to IVA once daily in the evening.

Number of subjects in period 1	ELX/TEZ/IVA	Placebo
Started	205	102
Completed	197	102
Not completed	8	0
Adverse Event	3	-
Death	1	-
Other	2	-
Withdrawal of consent (not due to AE)	2	-

Baseline characteristics

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Reporting group title

ELX/TEZ/IVA

Reporting group description

Subjects 6 to less than (<) 12 year of age and weighing <30 kilogram (kg) at Day 1 received ELX 100 milligram (mg)/TEZ 50 mg /IVA 75 mg as fixed dose combination (FDC) tablets in the morning and IVA as mono tablet in the evening and those weighing more than or equal to (≥) 30 kg at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 24 weeks. Subjects ≥12 years age at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 24 weeks.

Reporting group title

Placebo

Reporting group description

Subjects received placebo matched to ELX/TEZ/IVA FDC in the morning and placebo matched to IVA in the evening for 24 weeks.

Reporting group values	ELX/TEZ/IVA	Placebo	Total
Number of subjects	205	102	307
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	33.3 ( 15.9 )	33.9 ( 16.4 )	-
Gender categorical
Units: Subjects
Female	113	52	165
Male	92	50	142

End points

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Reporting group title

ELX/TEZ/IVA

Reporting group description

Subjects 6 to less than (<) 12 year of age and weighing <30 kilogram (kg) at Day 1 received ELX 100 milligram (mg)/TEZ 50 mg /IVA 75 mg as fixed dose combination (FDC) tablets in the morning and IVA as mono tablet in the evening and those weighing more than or equal to (≥) 30 kg at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 24 weeks. Subjects ≥12 years age at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 24 weeks.

Reporting group title

Placebo

Reporting group description

Subjects received placebo matched to ELX/TEZ/IVA FDC in the morning and placebo matched to IVA in the evening for 24 weeks.

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

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End point title

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

End point description

End point type

Primary

End point timeframe

From Baseline through Week 24

End point values	ELX/TEZ/IVA	Placebo
Number of subjects analysed	192	98
Units: percentage points
least squares mean (confidence interval 95%)	8.9 (7.7 to 10.0)	-0.4 (-2.0 to 1.3)

Statistical Analysis 1

Comparison groups

Placebo v ELX/TEZ/IVA

Number of subjects included in analysis

290

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed Models for Repeated Measures

Parameter type

LS Mean difference

Point estimate

9.2

Confidence interval

level

95%

sides

2-sided

lower limit

7.2

upper limit

11.3

Adverse events

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Timeframe for reporting adverse events

Day 1 up to Week 28

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.0

Reporting group title

ELX/TEZ/IVA

Reporting group description

Subjects 6 to <12 year of age and weighing <30 kg at Day 1 received ELX 100mg/TEZ 50 mg /IVA 75 mg as FDC tablets in the morning and IVA as mono tablet in the evening and those weighing ≥30 kg at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 24 weeks. Subjects ≥12 years age at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 24 weeks.

Reporting group title

Placebo

Reporting group description

Subjects received placebo matched to ELX/TEZ/IVA FDC in the morning and placebo matched to IVA in the evening for 24 weeks.

Serious adverse events	ELX/TEZ/IVA	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	18 / 205 (8.78%)	15 / 102 (14.71%)
number of deaths (all causes)	1	0
number of deaths resulting from adverse events	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma
subjects affected / exposed	1 / 205 (0.49%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Cardiac disorders
Stress cardiomyopathy
subjects affected / exposed	0 / 205 (0.00%)	1 / 102 (0.98%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Drug intolerance
subjects affected / exposed	0 / 205 (0.00%)	1 / 102 (0.98%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 205 (0.49%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	1 / 205 (0.49%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Subileus
subjects affected / exposed	1 / 205 (0.49%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	1 / 205 (0.49%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Haemoptysis
subjects affected / exposed	1 / 205 (0.49%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rash maculo-papular
subjects affected / exposed	1 / 205 (0.49%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Anxiety disorder
subjects affected / exposed	1 / 205 (0.49%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Post-traumatic stress disorder
subjects affected / exposed	1 / 205 (0.49%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Renal colic
subjects affected / exposed	0 / 205 (0.00%)	1 / 102 (0.98%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Polyarthritis
subjects affected / exposed	1 / 205 (0.49%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Bronchopulmonary aspergillosis allergic
subjects affected / exposed	2 / 205 (0.98%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 205 (0.49%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatitis viral
subjects affected / exposed	1 / 205 (0.49%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infective pulmonary exacerbation of cystic fibrosis
subjects affected / exposed	5 / 205 (2.44%)	13 / 102 (12.75%)
occurrences causally related to treatment / all	0 / 5	0 / 19
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 205 (0.49%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pseudomonas infection
subjects affected / exposed	1 / 205 (0.49%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vestibular neuronitis
subjects affected / exposed	1 / 205 (0.49%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	1 / 205 (0.49%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	ELX/TEZ/IVA	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	164 / 205 (80.00%)	86 / 102 (84.31%)
Nervous system disorders
Headache
subjects affected / exposed	37 / 205 (18.05%)	13 / 102 (12.75%)
occurrences all number	58	23
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	27 / 205 (13.17%)	14 / 102 (13.73%)
occurrences all number	34	17
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	17 / 205 (8.29%)	13 / 102 (12.75%)
occurrences all number	21	16
Abdominal pain upper
subjects affected / exposed	10 / 205 (4.88%)	7 / 102 (6.86%)
occurrences all number	11	8
Constipation
subjects affected / exposed	15 / 205 (7.32%)	4 / 102 (3.92%)
occurrences all number	22	4
Diarrhoea
subjects affected / exposed	26 / 205 (12.68%)	10 / 102 (9.80%)
occurrences all number	49	16
Vomiting
subjects affected / exposed	15 / 205 (7.32%)	7 / 102 (6.86%)
occurrences all number	16	10
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	36 / 205 (17.56%)	26 / 102 (25.49%)
occurrences all number	46	39
Haemoptysis
subjects affected / exposed	12 / 205 (5.85%)	6 / 102 (5.88%)
occurrences all number	16	8
Nasal congestion
subjects affected / exposed	6 / 205 (2.93%)	8 / 102 (7.84%)
occurrences all number	6	8
Oropharyngeal pain
subjects affected / exposed	17 / 205 (8.29%)	10 / 102 (9.80%)
occurrences all number	18	11
Productive cough
subjects affected / exposed	6 / 205 (2.93%)	6 / 102 (5.88%)
occurrences all number	6	6
Sputum increased
subjects affected / exposed	20 / 205 (9.76%)	13 / 102 (12.75%)
occurrences all number	25	20
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	45 / 205 (21.95%)	1 / 102 (0.98%)
occurrences all number	51	1
Infections and infestations
COVID-19
subjects affected / exposed	19 / 205 (9.27%)	10 / 102 (9.80%)
occurrences all number	19	10
Infective pulmonary exacerbation of cystic fibrosis
subjects affected / exposed	28 / 205 (13.66%)	36 / 102 (35.29%)
occurrences all number	36	52
Influenza
subjects affected / exposed	18 / 205 (8.78%)	2 / 102 (1.96%)
occurrences all number	20	2
Nasopharyngitis
subjects affected / exposed	42 / 205 (20.49%)	20 / 102 (19.61%)
occurrences all number	58	30
Rhinitis
subjects affected / exposed	20 / 205 (9.76%)	6 / 102 (5.88%)
occurrences all number	22	8
Upper respiratory tract infection
subjects affected / exposed	17 / 205 (8.29%)	10 / 102 (9.80%)
occurrences all number	17	12

More information

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Were there any global substantial amendments to the protocol? Yes

24 Jan 2022

Amended to add ELX/TEZ/IVA-responsive mutations to the list of qualifying CFTR mutations and adjust for the increased number of qualifying CFTR mutations, the maximum number of subjects with a given CFTR mutation that can be enrolled was decreased.

21 Apr 2022

Amended to maximum qualifying ppFEV1 value was expanded from 90% to 100%, specified that up to 10% of subjects may be enrolled with a screening ppFEV1 value >90% and ≤100% (approximately 27 subjects) and including history of hypersensitivity exclusion criterion and appendix to specify blood volumes.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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