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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03691779
Recruitment Status : Completed
First Posted : October 2, 2018
Results First Posted : October 22, 2021
Last Update Posted : October 22, 2021
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: ELX/TEZ/IVA Drug: IVA Phase 3

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 71 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
Actual Primary Completion Date : August 7, 2020
Actual Study Completion Date : August 7, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
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.
Drug: ELX/TEZ/IVA
Fixed-dose combination tablet orally once daily in the morning.
Other Names:
  • VX-445/VX-661/VX-770
  • elexacaftor/tezacaftor/ivacaftor

Drug: IVA
IVA tablet orally once daily in the evening.
Other Names:
  • VX-770
  • ivacaftor

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.
Drug: ELX/TEZ/IVA
Fixed-dose combination tablet orally once daily in the morning.
Other Names:
  • VX-445/VX-661/VX-770
  • elexacaftor/tezacaftor/ivacaftor

Drug: IVA
IVA tablet orally once daily in the evening.
Other Names:
  • VX-770
  • ivacaftor




Primary Outcome Measures :
  1. Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA [ Time Frame: Part A: Day 15 ]
  2. Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA [ Time Frame: Part A: Day 15 ]
  3. Part A: Area Under the Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24h) of ELX, TEZ, and IVA [ Time Frame: Part A: Day 15 ]
  4. Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Part B: Day 1 Through Safety Follow-up Visit (up to Week 28) ]

Secondary Outcome Measures :
  1. Part A: Cmax of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) [ Time Frame: Part A: Day 15 ]
  2. Part A: Ctrough of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) [ Time Frame: Part A: Day 15 ]
  3. Part A: AUC0-24h of ELX Metabolite (M23-ELX) and TEZ Metabolite (M1-TEZ) [ Time Frame: Part A: Day 15 ]
  4. Part A: Area Under the Concentration Versus Time Curve From 0 to 6 Hours (AUC0-6h) of IVA Metabolite (M1-IVA) [ Time Frame: Part A: Day 15 ]
    The AUC data was analyzed for up to 6 hours for IVA metabolite (M1-IVA). Therefore, AUC0-6h is reported for M1-IVA metabolite.

  5. Part A: Safety and Tolerability as Assessed by Number of Participants With TEAEs and SAEs [ Time Frame: Part A: Day 1 Through Safety Follow-up Visit (up to Day 43) ]
  6. Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [ Time Frame: Part B: From Baseline Through Week 24 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  7. Part B: Absolute Change in Sweat Chloride (SwCl) [ Time Frame: Part B: From Baseline Through Week 24 ]
    Sweat samples were collected using an approved collection device.

  8. Part B: Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score [ Time Frame: Part B: From Baseline Through Week 24 ]
    The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

  9. Part B: Absolute Change in Body Mass Index (BMI) [ Time Frame: Part B: From Baseline at Week 24 ]
    BMI was defined as weight in kg divided by squared height in meters (m^2).

  10. Part B: Absolute Change in BMI For-Age Z-Score [ Time Frame: Part B: From Baseline at Week 24 ]
    BMI was defined as weight in kg divided by squared height in meters (m^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.

  11. Part B: Absolute Change in Weight [ Time Frame: Part B: From Baseline at Week 24 ]
  12. Part B: Absolute Change in Weight-for-age Z-Score [ Time Frame: Part B: From Baseline at Week 24 ]
    The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.

  13. Part B: Absolute Change in Height [ Time Frame: Part B: From Baseline at Week 24 ]
  14. Part B: Absolute Change in Height-for-Age Z-Score [ Time Frame: Part B: From Baseline at Week 24 ]
    The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.

  15. Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale [ Time Frame: Part B: At Week 24 ]
    The study drug acceptability (participant reaction) was assessed by a visual analog scale that incorporates a 5 point facial hedonic scale (Liked it Very Much, Liked it a Little, Not sure, Disliked it a Little, Disliked it Very Much). Number of participants with the indicated categorical response in the drug acceptability assessment were reported.

  16. Part B: Number of Pulmonary Exacerbations Events [ Time Frame: Part B: From Baseline Through Week 24 ]
    Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria. The total number of pulmonary exacerbations events across all participants were reported.

  17. Part B: Number of CF Related Hospitalizations [ Time Frame: Part B: From Baseline Through Week 24 ]
    The total number of CF related hospitalization events across all participants were reported.

  18. Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) [ Time Frame: Part B: At Week 4 ]
  19. Part B: Absolute Change in Lung Clearance Index 2.5 (LCI2.5) [ Time Frame: Part B: From Baseline Through Week 24 ]
    LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.



Information from the National Library of Medicine

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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
  • 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


Locations
Show Show 21 study locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  Study Documents (Full-Text)

Documents provided by Vertex Pharmaceuticals Incorporated:
Study Protocol  [PDF] December 18, 2019
Statistical Analysis Plan  [PDF] August 11, 2020

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT03691779    
Other Study ID Numbers: VX18-445-106
2018-001695-38 ( EudraCT Number )
First Posted: October 2, 2018    Key Record Dates
Results First Posted: October 22, 2021
Last Update Posted: October 22, 2021
Last Verified: August 2021

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