A Phase 3 Study of VX-121 Combination Therapy in Particip... | NCT05033080

NCT05033080

ID	Type	Description	Link
2021-000712-31	EudraCT Number

Status Module

Oversight Module

Description 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
ELX/TEZ/IVA	Active Comparator	Following elexacftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) run-in period of 4 weeks, participants received ELX 200 milligram (mg) once daily (qd) /TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the treatment period for 52 weeks.	Drug: ELX/TEZ/IVA Drug: IVA Drug: Placebo (matched to VX-121/TEZ/D-IVA)
VX-121/TEZ/D-IVA	Experimental	Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.	Drug: VX-121/TEZ/D-IVA Drug: Placebo (matched to ELX/TEZ/IVA) Drug: Placebo (matched to IVA)

Name	Type	Description	Arm Group Labels	Other Names
VX-121/TEZ/D-IVA	Drug	Fixed-dose combination tablets for oral administration.	VX-121/TEZ/D-IVA

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 Through Week 24

Secondary Outcomes

Measure	Description	Time Frame
Absolute Change in Sweat Chloride (SwCl)	Sweat samples were collected using an approved collection device.	From Baseline Through Week 24
Percentage of Participants With SwCl <60 mmol/L (Pooled With Data From Study VX20-121-103)

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
39756424	Derived	Keating C, Yonker LM, Vermeulen F, Prais D, Linnemann RW, Trimble A, Kotsimbos T, Mermis J, Braun AT, O'Carroll M, Sutharsan S, Ramsey B, Mall MA, Taylor-Cousar JL, McKone EF, Tullis E, Floreth T, Michelson P, Sosnay PR, Nair N, Zahigian R, Martin H, Ahluwalia N, Lam A, Horsley A; VX20-121-102 Study Group; VX20-121-103 Study Group. Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials. Lancet Respir Med. 2025 Mar;13(3):256-271. doi: 10.1016/S2213-2600(24)00411-9. Epub 2025 Jan 2.
37983082

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	ELX/TEZ/IVA	Following elexacftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) run-in period of 4 weeks, participants received ELX 200 milligram (mg) once daily (qd) /TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the treatment period for 52 weeks.
FG001	VX-121/TEZ/D-IVA

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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	Aug 19, 2021	May 9, 2024

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Arm/Group Information

ID	Title	Description
BG000	ELX/TEZ/IVA	Following ELX/TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 52 weeks.
BG001	VX-121/TEZ/D-IVA	Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.
BG002	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
	OG0000.3(-0.3 to 0.9) OG0010.5(-0.1 to 1.1)

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 Models Repeated Measures		< 0.0001		LS Mean difference	0.2			2-Sided	95	-0.7	1.1					Non-Inferiority	The non-inferiority margin represents a clinically acceptable loss of effectiveness that margin preserve at least 50% of the treatment effect of the active control (ELX/TEZ/IVA) compared to placebo, where the treatment effect is estimated by the lower bound of the 95% confidence interval (CI).

Secondary

Absolute Change in Sweat Chloride (SwCl)

Sweat samples were collected using an approved collection device.

FAS. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure.

Posted

Least Squares Mean

95% Confidence Interval

millimole per liter (mmol/L)

From Baseline Through Week 24

ID	Title	Description
OG000	ELX/TEZ/IVA	Following ELX/TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 52 weeks.
OG001	VX-121/TEZ/D-IVA	Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With SwCl <60 mmol/L (Pooled With Data From Study VX20-121-103)

Sweat samples were collected using an approved collection device.

The Pooled Full Analysis Set (PFAS) included all randomized participants from this study (VX20-121-102) and from Study VX20-121-103 who carried the intended CFTR mutation(s) and received at least 1 dose of study drug during the Treatment Period. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this specific outcome measure.

Posted

Number

percentage of participants

From Baseline Through Week 24

ID	Title	Description
OG000	ELX/TEZ/IVA	Following ELX/TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 52 weeks.
OG001	VX-121/TEZ/D-IVA	Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.

Units	Counts
Participants

Secondary

Percentage of Participants With SwCl <30 mmol/L (Pooled With Data From Study VX20-121-103)

Sweat samples were collected using an approved collection device.

PFAS. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this specific outcome measure.

Posted

Number

percentage of participants

From Baseline Through Week 24

ID	Title	Description
OG000	ELX/TEZ/IVA	Following ELX/TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 52 weeks.
OG001	VX-121/TEZ/D-IVA	Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	ELX/TEZ/IVA	Following ELX/TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 52 weeks.	0	202	41	202	184	202
EG001	VNZ/TEZ/D-IVA	Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.	0	196	28	196	177	196

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Arteriospasm coronary	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Cerebrovascular arteriovenous malformation	Congenital, familial and genetic disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected202 at risk EG0011 affected196 at risk
Constipation	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0002 affected202 at risk EG0010 affected196 at risk
Distal intestinal obstruction syndrome	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0011 affected196 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Mechanical ileus	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected202 at risk EG0011 affected196 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected202 at risk EG0011 affected196 at risk
Subileus	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Cholestasis	Hepatobiliary disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected202 at risk EG0011 affected196 at risk
Hypersensitivity	Immune system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected202 at risk EG0011 affected196 at risk
Appendicitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0011 affected196 at risk
COVID-19	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0003 affected202 at risk EG0011 affected196 at risk
Cellulitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 affected202 at risk EG0011 affected196 at risk
Diverticulitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 affected202 at risk EG0011 affected196 at risk
Infective pulmonary exacerbation of cystic fibrosis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG00023 affected202 at risk EG00111 affected196 at risk
Influenza	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0013 affected196 at risk
Meningitis aseptic	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Pneumonia	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 affected202 at risk EG0012 affected196 at risk
Urinary tract infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 affected202 at risk EG0011 affected196 at risk
Viral myocarditis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 affected202 at risk EG0011 affected196 at risk
Alcohol poisoning	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Postoperative ileus	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Alanine aminotransferase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0002 affected202 at risk EG0010 affected196 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 affected202 at risk EG0011 affected196 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Pulmonary function test decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Hyperphosphatasaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected202 at risk EG0011 affected196 at risk
Adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.1	Systematic Assessment	EG0000 affected202 at risk EG0011 affected196 at risk
Epilepsy	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Headache	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected202 at risk EG0011 affected196 at risk
Serotonin syndrome	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Syncope	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected202 at risk EG0012 affected196 at risk
Behaviour disorder	Psychiatric disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Depression	Psychiatric disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected202 at risk EG0011 affected196 at risk
Depression suicidal	Psychiatric disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Mixed anxiety and depressive disorder	Psychiatric disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk
Suicidal ideation	Psychiatric disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0012 affected196 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0002 affected202 at risk EG0012 affected196 at risk
Nasal polyps	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected202 at risk EG0010 affected196 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal distension	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG00010 affected202 at risk EG0015 affected196 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG00014 affected202 at risk EG00110 affected196 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0006 affected202 at risk EG00112 affected196 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG00015 affected202 at risk EG00121 affected196 at risk
Nausea	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG00017 affected202 at risk EG0017 affected196 at risk
Fatigue	General disorders	MedDRA 26.1	Systematic Assessment	EG00016 affected202 at risk EG00118 affected196 at risk
Pyrexia	General disorders	MedDRA 26.1	Systematic Assessment	EG00021 affected202 at risk EG00124 affected196 at risk
COVID-19	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG00053 affected202 at risk EG00149 affected196 at risk
Infective pulmonary exacerbation of cystic fibrosis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG00064 affected202 at risk EG00153 affected196 at risk
Influenza	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG00010 affected202 at risk EG00117 affected196 at risk
Nasopharyngitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG00035 affected202 at risk EG00145 affected196 at risk
Respiratory tract infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG00012 affected202 at risk EG0018 affected196 at risk
Sinusitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG00010 affected202 at risk EG00110 affected196 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG00027 affected202 at risk EG00117 affected196 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG00018 affected202 at risk EG00117 affected196 at risk
Alanine aminotransferase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG00010 affected202 at risk EG00113 affected196 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0008 affected202 at risk EG00112 affected196 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG00023 affected202 at risk EG00118 affected196 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG00011 affected202 at risk EG00110 affected196 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG00016 affected202 at risk EG0019 affected196 at risk
Headache	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG00022 affected202 at risk EG00125 affected196 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG00041 affected202 at risk EG00145 affected196 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG00010 affected202 at risk EG00113 affected196 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG00024 affected202 at risk EG00119 affected196 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG00023 affected202 at risk EG00124 affected196 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0005 affected202 at risk EG00112 affected196 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG00014 affected202 at risk EG00119 affected196 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0005 affected202 at risk EG00114 affected196 at risk
Sputum increased	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG00021 affected202 at risk EG00118 affected196 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0009 affected202 at risk EG00112 affected196 at risk

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
C000706587	elexacaftor, ivacaftor, tezacaftor drug combination
C545203	ivacaftor