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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

Brief Summary:
A Rollover Safety Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for F508del.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: LUM/IVA Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 57 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 12, 2017
Actual Primary Completion Date : July 17, 2019
Actual Study Completion Date : July 17, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis
Drug Information available for: Ivacaftor

Arm Intervention/treatment
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.
Drug: LUM/IVA
Participants received LUM/IVA every q12h.
Other Names:
  • VX-809/VX-770
  • lumacaftor/ivacaftor




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Absolute Change in Sweat Chloride [ Time Frame: From Parent Study 115B Baseline at Week 96 ]
    Sweat samples were collected using an approved collection device.

  2. 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).

  3. 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.

  4. Absolute Change in Weight [ Time Frame: From Parent Study 115B Baseline at Week 96 ]
  5. 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.

  6. Absolute Change From Baseline in Stature (Height) [ Time Frame: From Parent Study 115B Baseline at Week 96 ]
  7. 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.

  8. 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.

  9. 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.

  10. Number of Cystic Fibrosis (CF) Related Hospitalizations [ Time Frame: From Parent Study 115B Baseline through Week 96 ]
  11. Absolute Change in Fecal Elastase-1 (FE-1) Levels [ Time Frame: From Parent Study 115B Baseline at Week 96 ]
  12. Absolute Change in Immunoreactive Trypsinogen (IRT) Serum Levels [ Time Frame: From Parent Study 115B Baseline at Week 96 ]
  13. 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.

  14. 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.

  15. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT03125395


Locations
Show Show 20 study locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  Study Documents (Full-Text)

Documents provided by Vertex Pharmaceuticals Incorporated:
Study Protocol  [PDF] October 10, 2016
Statistical Analysis Plan  [PDF] May 20, 2019

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Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT03125395    
Other Study ID Numbers: VX16-809-116
2019-003112-31 ( EudraCT Number )
First Posted: April 24, 2017    Key Record Dates
Results First Posted: August 7, 2020
Last Update Posted: August 7, 2020
Last Verified: July 2020

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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
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action