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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03691779

Registration number

NCT03691779

Ethics application status

Date submitted

28/09/2018

Date registered

2/10/2018

Date last updated

22/10/2021

Titles & IDs

Public title

Evaluation of VX 445/TEZ/IVA in Cystic Fibrosis Subjects 6 Through 11 Years of Age

Scientific title

A Phase 3 Study Evaluating the Pharmacokinetics, Safety, and Tolerability of VX-445/TEZ/IVA Triple Combination Therapy in Cystic Fibrosis Subjects 6 Through 11 Years of Age

Secondary ID [1]

2018-001695-38

Secondary ID [2]

VX18-445-106

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Cystic Fibrosis

Condition category

Condition code

Human Genetics and Inherited Disorders

Cystic fibrosis

Respiratory

Other respiratory disorders / diseases

Oral and Gastrointestinal

Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Inflammatory and Immune System

Connective tissue diseases

Inflammatory and Immune System

Other inflammatory or immune system disorders

Intervention/exposure

Study type

Interventional(has expanded access)

Description of intervention(s) / exposure

Treatment: Drugs - ELX/TEZ/IVA
Treatment: Drugs - IVA

Experimental: Part A: ELX/TEZ/IVA - Participants in Part A received ELX 100 milligrams (mg) once daily (qd)/TEZ 50 mg qd/IVA 75 mg every 12 hours (q12h) in the treatment period for 15 days.

Experimental: Part B: ELX/TEZ/IVA - Participants in Part B weighing less than (\<) 30 kilograms (kg) at Day 1 received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing greater than equals to (\>=) 30 kg at Day 1 received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.

Treatment: Drugs: ELX/TEZ/IVA
Fixed-dose combination tablet orally once daily in the morning.

Treatment: Drugs: IVA
IVA tablet orally once daily in the evening.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA

Timepoint [1]

Part A: Day 15

Primary outcome [2]

Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA

Timepoint [2]

Part A: Day 15

Primary outcome [3]

Part A: Area Under the Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24h) of ELX, TEZ, and IVA

Timepoint [3]

Part A: Day 15

Primary outcome [4]

Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Timepoint [4]

Part B: Day 1 Through Safety Follow-up Visit (up to Week 28)

Secondary outcome [1]

Part A: Cmax of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)

Timepoint [1]

Part A: Day 15

Secondary outcome [2]

Part A: Ctrough of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)

Timepoint [2]

Part A: Day 15

Secondary outcome [3]

Part A: AUC0-24h of ELX Metabolite (M23-ELX) and TEZ Metabolite (M1-TEZ)

Timepoint [3]

Part A: Day 15

Secondary outcome [4]

Part A: Area Under the Concentration Versus Time Curve From 0 to 6 Hours (AUC0-6h) of IVA Metabolite (M1-IVA)

Timepoint [4]

Part A: Day 15

Secondary outcome [5]

Part A: Safety and Tolerability as Assessed by Number of Participants With TEAEs and SAEs

Timepoint [5]

Part A: Day 1 Through Safety Follow-up Visit (up to Day 43)

Secondary outcome [6]

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

Timepoint [6]

Part B: From Baseline Through Week 24

Secondary outcome [7]

Part B: Absolute Change in Sweat Chloride (SwCl)

Timepoint [7]

Part B: From Baseline Through Week 24

Secondary outcome [8]

Part B: Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score

Timepoint [8]

Part B: From Baseline Through Week 24

Secondary outcome [9]

Part B: Absolute Change in Body Mass Index (BMI)

Timepoint [9]

Part B: From Baseline at Week 24

Secondary outcome [10]

Part B: Absolute Change in BMI For-Age Z-Score

Timepoint [10]

Part B: From Baseline at Week 24

Secondary outcome [11]

Part B: Absolute Change in Weight

Timepoint [11]

Part B: From Baseline at Week 24

Secondary outcome [12]

Part B: Absolute Change in Weight-for-age Z-Score

Timepoint [12]

Part B: From Baseline at Week 24

Secondary outcome [13]

Part B: Absolute Change in Height

Timepoint [13]

Part B: From Baseline at Week 24

Secondary outcome [14]

Part B: Absolute Change in Height-for-Age Z-Score

Timepoint [14]

Part B: From Baseline at Week 24

Secondary outcome [15]

Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale

Timepoint [15]

Part B: At Week 24

Secondary outcome [16]

Part B: Number of Pulmonary Exacerbations Events

Timepoint [16]

Part B: From Baseline Through Week 24

Secondary outcome [17]

Part B: Number of CF Related Hospitalizations

Timepoint [17]

Part B: From Baseline Through Week 24

Secondary outcome [18]

Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA)

Timepoint [18]

Part B: At Week 4

Secondary outcome [19]

Part B: Absolute Change in Lung Clearance Index 2.5 (LCI2.5)

Timepoint [19]

Part B: From Baseline Through Week 24

Eligibility

Key inclusion criteria

Key

* Homozygous or heterozygous for F508del mutation (F/F or F/MF genotypes)
* Forced expiratory volume in 1 second (FEV1) value =40% of predicted mean for age, sex, and height.

Key

Minimum age

6 Years

Maximum age

11 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

* Clinically significant cirrhosis with or without portal hypertension
* Lung infection with organisms associated with a more rapid decline in pulmonary status.
* Solid organ or hematological transplantation.

Other protocol defined Inclusion/Exclusion criteria may apply.

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Other

Other design features

Phase

Phase 3

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

2/10/2018

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

7/08/2020

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Queensland Children's Hospital - South Brisbane

Recruitment hospital [2]

The Children's Hospital at Westmead - Westmead

Recruitment postcode(s) [1]

- South Brisbane

Recruitment postcode(s) [2]

- Westmead

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

California

Country [2]

United States of America

State/province [2]

Colorado

Country [3]

United States of America

State/province [3]

Illinois

Country [4]

United States of America

State/province [4]

Massachusetts

Country [5]

United States of America

State/province [5]

Minnesota

Country [6]

United States of America

State/province [6]

Missouri

Country [7]

United States of America

State/province [7]

New York

Country [8]

United States of America

State/province [8]

North Carolina

Country [9]

United States of America

State/province [9]

Ohio

Country [10]

United States of America

State/province [10]

Oregon

Country [11]

United States of America

State/province [11]

Texas

Country [12]

United States of America

State/province [12]

Washington

Country [13]

Canada

State/province [13]

Toronto

Country [14]

Canada

State/province [14]

Vancouver

Country [15]

Ireland

State/province [15]

Dublin

Country [16]

United Kingdom

State/province [16]

Birmingham

Country [17]

United Kingdom

State/province [17]

London

Funding & Sponsors

Primary sponsor type

Commercial sector/industry

Name

Vertex Pharmaceuticals Incorporated

Address

Country

Ethics approval

Ethics application status

Summary

Brief summary

This study will evaluate the pharmacokinetics (PK), safety, tolerability, efficacy, and pharmacodynamic effect of VX-445, tezacaftor (TEZ), and ivacaftor (IVA) when dosed in triple combination (TC) in Cystic Fibrosis (CF) subjects 6 through 11 years of age with F/F and F/MF genotypes.

Trial website

https://clinicaltrials.gov/study/NCT03691779

Trial related presentations / publications

Zemanick ET, Taylor-Cousar JL, Davies J, Gibson RL, Mall MA, McKone EF, McNally P, Ramsey BW, Rayment JH, Rowe SM, Tullis E, Ahluwalia N, Chu C, Ho T, Moskowitz SM, Noel S, Tian S, Waltz D, Weinstock TG, Xuan F, Wainwright CE, McColley SA. A Phase 3 Open-Label Study of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One F508del Allele. Am J Respir Crit Care Med. 2021 Jun 15;203(12):1522-1532. doi: 10.1164/rccm.202102-0509OC.
Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.

Public notes

Contacts

Principal investigator

Name

Address

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

No information has been provided regarding IPD availability

What supporting documents are/will be available?

Type	Other Details	Attachment
Study protocol		https://cdn.clinicaltrials.gov/large-docs/79/NCT03691779/Prot_000.pdf
Statistical analysis plan		https://cdn.clinicaltrials.gov/large-docs/79/NCT03691779/SAP_001.pdf

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT03691779

Trial Review

Registering a new trial?

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03691779