Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03691779
Recruitment Status : Recruiting
First Posted : October 2, 2018
Last Update Posted : September 13, 2019
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

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.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: VX-445 Drug: TEZ Drug: IVA Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : October 2, 2018
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
Experimental: Part A: Triple Combination
Subjects will receive 100 mg VX-445/ 50 mg TEZ/ 75 mg IVA as an FDC tablet in the morning and 75 mg IVA as mono tablet in the evening.
Drug: VX-445
Fixed dose combination (FDC) tablet (VX-445/TEZ/IVA)

Drug: TEZ
FDC tablet (VX-445/TEZ/IVA)
Other Name: tezacaftor; VX-661

Drug: IVA
FDC tablet (VX-445/TEZ/IVA) and IVA mono tablet
Other Name: ivacaftor; VX-770

Experimental: Part B: Triple Combination
Subjects will receive VX-445/TEZ/IVA as FDC tablet in the morning and IVA as mono tablet in the evening with the dose to be based on the outcome of Part A.
Drug: VX-445
Fixed dose combination (FDC) tablet (VX-445/TEZ/IVA)

Drug: TEZ
FDC tablet (VX-445/TEZ/IVA)
Other Name: tezacaftor; VX-661

Drug: IVA
FDC tablet (VX-445/TEZ/IVA) and IVA mono tablet
Other Name: ivacaftor; VX-770




Primary Outcome Measures :
  1. Part A: Observed pre-dose concentration (Ctrough) of VX-445, TEZ, and IVA [ Time Frame: Day 1 through 15 ]
  2. Part A: Maximum Observed Concentration (Cmax) of VX-445, TEZ, and IVA [ Time Frame: Day 1 through 15 ]
  3. Part A: Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-445, TEZ, and IVA [ Time Frame: Day 1 through 15 ]
  4. Part B: Safety and tolerability as assessed by number of subjects with adverse events and serious adverse events [ Time Frame: from baseline through safety follow-up (28 Weeks) ]

Secondary Outcome Measures :
  1. Part A: Maximum observed concentration (Cmax) of VX-445, TEZ, and IVA metabolites [ Time Frame: from Day 1 through 15 ]
  2. Part A: Observed pre-dose concentration (Ctrough) of VX-445, TEZ, and IVA metabolites [ Time Frame: from Day 1 through 15 ]
  3. Part A: Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-445, TEZ, and IVA metabolites [ Time Frame: from Day 1 through 15 ]
  4. Part A: Safety and tolerability as assessed by number of subjects with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: from baseline through safety follow-up (28 Weeks) ]
  5. Part B: Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) [ Time Frame: from baseline through Weeks 12 and 24 ]
  6. Part B: Absolute change in sweat chloride [ Time Frame: from baseline through Weeks 12 and 24 ]
  7. Part B: Absolute change in Cystic Fibrosis Questionnaire Revised (CFQ R) respiratory domain score [ Time Frame: from baseline through Weeks 12 and 24 ]
  8. Part B: Absolute change in body mass index (BMI) and BMI for age-z-score [ Time Frame: from baseline at Week 24 ]
  9. Part B: Absolute change in weight and weight for age-z-score [ Time Frame: from baseline at Week 24 ]
  10. Part B: Absolute change in height and height for age-z-score [ Time Frame: from baseline at Week 24 ]
  11. Part B: Absolute change in the Modified Facial Hedonic Scale [ Time Frame: from baseline at Week 24 ]
  12. Parts B: Ctrough of VX-445, TEZ, IVA, and IVA metabolites [ Time Frame: Day 1 through Week 24 ]
  13. Part B: Absolute change in lung clearance index2.5 (LCI2.5) [ Time Frame: from baseline through Week 24 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Years to 11 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • 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 Exclusion Criteria:

  • Clinically significant cirrhosis with or without portal hypertension
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03691779


Contacts
Layout table for location contacts
Contact: Medical Information 6173416777 medicalinfo@vrtx.com

Locations
Layout table for location information
United States, California
Children's Hospital of Orange County Recruiting
Orange, California, United States, 92868
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
United States, Minnesota
Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55404
United States, New York
Northwell Health- Long Island Jewish Medical Center Recruiting
New Hyde Park, New York, United States, 11040
United States, Ohio
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated

Layout table for additonal information
Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT03691779     History of Changes
Other Study ID Numbers: VX18-445-106
2018-001695-38 ( EudraCT Number )
First Posted: October 2, 2018    Key Record Dates
Last Update Posted: September 13, 2019
Last Verified: September 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Ivacaftor
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action