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A Phase 3 Study of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)

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: NCT03525444
Recruitment Status : Completed
First Posted : May 15, 2018
Results First Posted : May 6, 2020
Last Update Posted : May 19, 2020
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Tracking Information
First Submitted Date  ICMJE May 2, 2018
First Posted Date  ICMJE May 15, 2018
Results First Submitted Date  ICMJE April 22, 2020
Results First Posted Date  ICMJE May 6, 2020
Last Update Posted Date May 19, 2020
Actual Study Start Date  ICMJE June 15, 2018
Actual Primary Completion Date April 24, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 22, 2020)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [ Time Frame: From Baseline at Week 4 ]
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Original Primary Outcome Measures  ICMJE
 (submitted: May 2, 2018)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [ Time Frame: From Baseline at Week 4 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2020)
  • Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [ Time Frame: From Baseline through Week 24 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
  • Number of Pulmonary Exacerbations (PEx) [ Time Frame: From Baseline through Week 24 ]
    Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
  • Absolute Change in Sweat Chloride (SwCl) [ Time Frame: From Baseline through Week 24 ]
    Sweat samples were collected using an approved collection device.
  • Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score [ Time Frame: 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.
  • Absolute Change in Body Mass Index (BMI) [ Time Frame: From Baseline at Week 24 ]
    BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).
  • Absolute Change in Sweat Chloride [ Time Frame: From Baseline at Week 4 ]
    Sweat samples were collected using an approved collection device.
  • Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score [ Time Frame: From Baseline at Week 4 ]
    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.
  • Time-to-first Pulmonary Exacerbation (PEx) [ Time Frame: From Baseline through Week 24 ]
    Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
  • Absolute Change in BMI Z-score for Participants <=20 Years of Age at Baseline [ Time Frame: From Baseline at Week 24 ]
    BMI was defined as weight in kg divided by height in m^2. Z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI.
  • Absolute Change in Body Weight [ Time Frame: From Baseline at Week 24 ]
  • Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 28 weeks) ]
  • Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ, M1-TEZ, and IVA [ Time Frame: Pre-dose on Week 4, 8, 12, and 16 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 2, 2018)
  • Absolute change in ppFEV1 [ Time Frame: From Baseline through Week 24 ]
  • Number of Pulmonary Exacerbations (PEx) [ Time Frame: From Baseline through Week 24 ]
  • Absolute Change in Body Mass Index (BMI) [ Time Frame: From Baseline at Week 24 ]
  • Absolute Change in Sweat Chloride (SwCl) [ Time Frame: from baseline at Week 4 and through Week 24 ]
  • Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score [ Time Frame: from baseline at Week 4 and through Week 24 ]
  • Time-to-first PEx [ Time Frame: through Week 24 ]
  • Absolute change in BMI z-score [ Time Frame: from baseline at Week 24 ]
  • Absolute Change in Body Weight [ Time Frame: From Baseline at Week 24 ]
  • Safety and tolerability as assessed by number of subjects with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: from baseline through 4-week safety follow-up (up to 28 weeks) ]
  • Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ, M1-TEZ, and IVA [ Time Frame: from Day 1 through Week 16 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 3 Study of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
Official Title  ICMJE A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
Brief Summary This study will evaluate the efficacy of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function mutation (F/MF subjects).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Cystic Fibrosis
Intervention  ICMJE
  • Drug: VX-445/TEZ/IVA
    Participants received VX-445/TEZ/IVA orally once daily in the morning.
    Other Names:
    • VX-445/VX-661/VX-770
    • VX-445/tezacaftor/ivacaftor
  • Drug: IVA
    Participants received IVA orally once daily in the evening
    Other Names:
    • VX-770
    • ivacaftor
  • Drug: Placebo
    Participants received placebo matched VX-445/TEZ/IVA orally once daily in the morning and placebo matched to IVA orally once daily in the evening.
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Participants who received placebo matched to VX-445/TEZ/IVA for 24 weeks in the TC treatment period.
    Intervention: Drug: Placebo
  • Experimental: VX-445/TEZ/IVA TC
    Participants who received VX-445 200 mg/TEZ 100 mg/IVA150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period.
    Interventions:
    • Drug: VX-445/TEZ/IVA
    • Drug: IVA
Publications * Middleton PG, Mall MA, Dřevínek P, Lands LC, McKone EF, Polineni D, Ramsey BW, Taylor-Cousar JL, Tullis E, Vermeulen F, Marigowda G, McKee CM, Moskowitz SM, Nair N, Savage J, Simard C, Tian S, Waltz D, Xuan F, Rowe SM, Jain R; VX17-445-102 Study Group. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019 Nov 7;381(19):1809-1819. doi: 10.1056/NEJMoa1908639. Epub 2019 Oct 31.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 3, 2018)
405
Original Estimated Enrollment  ICMJE
 (submitted: May 2, 2018)
360
Actual Study Completion Date  ICMJE April 24, 2019
Actual Primary Completion Date April 24, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Heterozygous for the F508del mutation (F/MF)
  • Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% 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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   Czechia,   France,   Germany,   Greece,   Italy,   Netherlands,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03525444
Other Study ID Numbers  ICMJE VX17-445-102
2018-000183-28 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Vertex Pharmaceuticals Incorporated
Study Sponsor  ICMJE Vertex Pharmaceuticals Incorporated
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Vertex Pharmaceuticals Incorporated
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP