Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Rollover Safety Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation

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: NCT03125395
Recruitment Status : Completed
First Posted : April 24, 2017
Results First Posted : August 7, 2020
Last Update Posted : August 7, 2020
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Tracking Information
First Submitted Date  ICMJE April 19, 2017
First Posted Date  ICMJE April 24, 2017
Results First Submitted Date  ICMJE July 15, 2020
Results First Posted Date  ICMJE August 7, 2020
Last Update Posted Date August 7, 2020
Actual Study Start Date  ICMJE May 12, 2017
Actual Primary Completion Date July 17, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 15, 2020)
Safety as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to Week 98 ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 21, 2017)
Safety and tolerability assessments based on the number of subjects with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: From baseline through safety follow-up (up to 98 weeks). ]
Number of subjects with AEs and SAEs will be reported.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2020)
  • Absolute Change in Sweat Chloride [ Time Frame: From Parent Study 115B Baseline at Week 96 ]
    Sweat samples were collected using an approved collection device.
  • Absolute Change in Body Mass Index (BMI) [ Time Frame: From Parent Study 115B Baseline at Week 96 ]
    BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).
  • Absolute Change in BMI-for-age Z-score [ Time Frame: From Parent Study 115B Baseline at Week 96 ]
    BMI was defined as weight in kilograms divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. 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.
  • Absolute Change in Weight [ Time Frame: From Parent Study 115B Baseline at Week 96 ]
  • Absolute Change in Weight-for-age Z-score [ Time Frame: From Parent Study 115B Baseline at Week 96 ]
    Z-score is a statistical measure to describe whether a mean was above or below the standard. 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.
  • Absolute Change From Baseline in Stature (Height) [ Time Frame: From Parent Study 115B Baseline at Week 96 ]
  • Absolute Change in Stature-for-age Z-score [ Time Frame: From Parent Study 115B Baseline at Week 96 ]
    Z-score is a statistical measure to describe whether a mean was above or below the standard. 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.
  • Time-to-first Pulmonary Exacerbation [ Time Frame: From Parent Study 115B Baseline through Week 96 ]
    Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol-defined criteria.
  • Number of Pulmonary Exacerbations (PEx) [ Time Frame: From Parent Study 115B Baseline through Week 96 ]
    Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol-defined criteria.
  • Number of Cystic Fibrosis (CF) Related Hospitalizations [ Time Frame: From Parent Study 115B Baseline through Week 96 ]
  • Absolute Change in Fecal Elastase-1 (FE-1) Levels [ Time Frame: From Parent Study 115B Baseline at Week 96 ]
  • Absolute Change in Immunoreactive Trypsinogen (IRT) Serum Levels [ Time Frame: From Parent Study 115B Baseline at Week 96 ]
  • Number of Participants With Microbiology Culture Status (Positive or Negative) [ Time Frame: Week 96 ]
    Following microbial tests were performed: Burkholderia, Methicillin Resistant Staphylococcus Aureus (MRSA), Methicillin Susceptible Staphylococcus Aureus (MSSA), Pseudomonas Aeruginosa Mucoid (P. Aeruginosa Mucoid), P. Aeruginosa Non-Mucoid, P. Aeruginosa Small Colony Variant and Stenotrophomonas Maltophilia.
  • Absolute Change in Lung Clearance Index (LCI) 2.5 [ Time Frame: From Parent Study 115B Baseline at Week 96 ]
    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.
  • Absolute Change in Lung Clearance Index (LCI) 5.0 [ Time Frame: From Parent Study 115B Baseline at Week 96 ]
    LCI 5.0 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 21, 2017)
  • Absolute change from baseline in sweat chloride [ Time Frame: From baseline through 96 weeks. ]
    Sweat samples will be collected using an approved collection device. Absolute change in sweat chloride will be reported.
  • Absolute change from baseline in body mass index (BMI) [ Time Frame: From baseline through 96 weeks. ]
    BMI is defined as weight in kilogram (kg) divided by height*height in square meter (m^2). Absolute change in BMI will be reported.
  • Absolute change from baseline in BMI-for-age Z-score [ Time Frame: From baseline through 96 weeks. ]
    BMI is defined as weight in kg divided by height*height in m^2. Z-score is a statistical measure to evaluate how a single data point compares to a standard. Absolute change in BMI-for-age Z-score will be reported.
  • Absolute change from baseline in weight [ Time Frame: From baseline through 96 weeks. ]
    Weight will be measured in kg and absolute change will be reported.
  • Absolute change from baseline in weight-for-age Z-score [ Time Frame: From baseline through 96 weeks. ]
    Weight will be measured in kg. Z-score is a statistical measure to evaluate how a single data point compares to a standard. Absolute change in weight-for-age Z-score will be reported.
  • Absolute change from baseline in stature [ Time Frame: From baseline through 96 weeks. ]
    Stature (height) will be measured in centimeter (cm) and absolute change will be reported.
  • Absolute change from baseline in stature-for-age Z-score [ Time Frame: From baseline through 96 weeks. ]
    Stature (height) will be measured in cm. Z-score is a statistical measure to evaluate how a single data point compares to a standard. Absolute change in stature-for-age Z-score will be reported.
  • Time-to-first Pulmonary Exacerbation [ Time Frame: From baseline through 96 weeks. ]
    Pulmonary exacerbation refers to the intermittent episodes of acute decline of lung function and worsening of symptoms. Time to first pulmonary exacerbation will be reported.
  • Number of pulmonary exacerbations [ Time Frame: From baseline through 96 weeks. ]
    Pulmonary exacerbation refers to the intermittent episodes of acute decline of lung function and worsening of symptoms. Number of pulmonary exacerbations during the study will be reported.
  • Number of Cystic Fibrosis (CF) Related Hospitalizations [ Time Frame: From baseline through 96 weeks. ]
    Number of hospitalizations due to CF during the study will be reported.
  • Absolute change from baseline in fecal elastase-1 (FE-1) levels [ Time Frame: From baseline through 96 weeks. ]
    Absolute change in FE-1 levels will be reported.
  • Absolute change from baseline in serum levels of immunoreactive trypsinogen (IRT) [ Time Frame: From baseline through 96 weeks. ]
    Absolute change in IRT serum levels will be reported.
  • Change from baseline in sputum microbiology cultures [ Time Frame: From baseline through 96 weeks. ]
    Change in sputum microbiology cultures will be reported.
  • Absolute change from baseline in lung clearance index (LCI)2.5 [ Time Frame: From baseline through 96 weeks. ]
    LCI is a measure of ventilation inhomogeneity that is based on tidal breathing techniques. LCI 2.5 will be defined as the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value. Absolute change in LCI2.5 will be reported.
  • Absolute change from baseline in LCI5.0 [ Time Frame: From baseline through 96 weeks. ]
    LCI is a measure of ventilation inhomogeneity that is based on tidal breathing techniques. LCI 5.0 will be defined as the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value. Absolute change in LCI5.0 will be reported.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Rollover Safety Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
Official Title  ICMJE A Phase 3, Rollover Study to Evaluate the Safety of Long-term Treatment With Lumacaftor/Ivacaftor Combination Therapy in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
Brief Summary A Rollover Safety Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for F508del.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cystic Fibrosis
Intervention  ICMJE Drug: LUM/IVA
Participants received LUM/IVA every q12h.
Other Names:
  • VX-809/VX-770
  • lumacaftor/ivacaftor
Study Arms  ICMJE Experimental: LUM/IVA
LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.
Intervention: Drug: LUM/IVA
Publications * Hoppe JE, Chilvers M, Ratjen F, McNamara JJ, Owen CA, Tian S, Zahigian R, Cornell AG, McColley SA. Long-term safety of lumacaftor-ivacaftor in children aged 2-5 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a multicentre, phase 3, open-label, extension study. Lancet Respir Med. 2021 May 6. pii: S2213-2600(21)00069-2. doi: 10.1016/S2213-2600(21)00069-2. [Epub ahead of print]

*   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 18, 2017)
57
Original Estimated Enrollment  ICMJE
 (submitted: April 21, 2017)
56
Actual Study Completion Date  ICMJE July 17, 2019
Actual Primary Completion Date July 17, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Subjects entering the Treatment Cohort must meet the following criteria:

  • Completed 24 weeks of LUM/IVA treatment and the Safety Follow-up Visit in Study VX15-809-115 Part B (Study 115B, NCT02797132)
  • Willing to remain on a stable CF medication regimen through the Safety Follow-up Visit

Subjects entering the Observational Cohort must meet 1 of the following criteria:

  • Completed 24 weeks of LUM/IVA treatment and the Safety Follow-up Visit in Study 115B, but do not want to enroll in the Treatment Cohort.
  • Received at least 4 weeks of LUM/IVA treatment and completed visits up to Week 24 and the Safety Follow-up Visit, if required, of Study 115B but are not taking LUM/IVA at the end of the Study 115B Treatment Period (i.e., Week 24) because of a drug interruption and either did not receive Vertex approval to enroll in the Treatment Cohort or do not want to enroll in the Treatment Cohort.
  • Permanently discontinued LUM/IVA in Study 115B after receiving at least 4 weeks of treatment and remained in the study from the time of treatment discontinuation through the Week 24 Visit and Safety Follow-up Visit, if required.

Exclusion Criteria (Treatment Cohort Only):

  • Prematurely discontinued LUM/IVA treatment in Study 115B.
  • History of any comorbidity or laboratory abnormality that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering LUM/IVA to the subject
  • History of drug intolerance or other serious reactions to LUM/IVA in Study 115B that would pose an additional risk to the subject in the opinion of investigator, and which should be discussed with the Vertex medical monitor.
  • Subjects with a history of allergy or hypersensitivity to LUM/IVA.
  • Liver function test (LFT) abnormality meeting criteria for LUM/IVA treatment interruption at the completion of Study 115B, for which no convincing alternative etiology is identified.
  • QTc value at the completion of Study 115B that would pose an additional risk to the subject in the opinion of investigator, and which should be discussed with the Vertex medical monitor
  • History of poor compliance with LUM/IVA and/or procedures in Study 115B as deemed by the investigator.
  • Participation in an investigational drug trial (including studies investigating LUM and/or IVA) other than Study 115B.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 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 Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03125395
Other Study ID Numbers  ICMJE VX16-809-116
2019-003112-31 ( 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 July 2020

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