An Observational Study to Evaluate the Long-term Safety of Ivacaftor in Patients With Cystic Fibrosis

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Drug utilisation

  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Post-authorisation safety study

Study drug and medical condition

• Name of medicine:
  KALYDECO
• Medical condition to be studied:
  Cystic fibrosis

Population studied

• Short description of the study population:
  The Ivacaftor Cohort will include all patients who have been treated with ivacaftor and are enrolled in the CF Trust or CF Foundation patient registries. The Comparator Cohort will include patients who have never been exposed to ivacaftor and are matched on age group, CFTR genotype class, and sex to patients in the Ivacaftor Cohort. The Ivacaftor Pregnancy Study Cohort will include all female patients who have ivacaftor exposure in the analysis year and are enrolled in the CF Trust or CF Foundation patient registries. The Comparator Pregnancy Study Cohort will include female patients who have never been exposed to ivacaftor and are matched on CFTR genotype class to patients in the Ivacaftor Pregnancy Study Cohort. The Comparator and Comparator Pregnancy Study Cohorts will be identified for each registry's Ivacaftor and Ivacaftor Pregnancy Study Cohorts, respectively, at a ratio of m:1, where m is the maximum number of matches available. The Historical Cohort will include patients who have the G551D-CFTR mutation, were enrolled in the patient registries before ivacaftor was available in clinical studies and commercially in the US and the UK (i.e., 2008), and were never exposed to ivacaftor. The Drug Utilisation Cohort will include all patients who have ever been treated with ivacaftor.
• Age groups:
  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Hepatic impaired

  Immunocompromised

  Pregnant women

  Renal impaired
• Estimated number of subjects:
  1654

Study design details

• Main study objective:
  To evaluate the long-term safety of ivacaftor in patients with CF,To evaluate outcomes of pregnancy in ivacaftor-treated patients,To evaluate the drug utilisation of ivacaftor,To evaluate CF disease progression in ivacaftor treated patients.
• Outcomes:
  Safety outcomes: death, organ transplant, hospitalisations, CF complications, pulmonary exacerbations and respiratory microbiology and serious safety outcomes.Pregnancy outcomes: pregnancy, live birth, stillbirth, spontaneous abortion, therapeutic abortion, gestational age, congenital anomalies.Drug utilisation: ivacaftor exposure.CF progression: lung disease severity, lung function change.
• Data analysis plan:
  Data for safety-related outcomes will be analysed separately for each registry for 5 years (data "extraction" in 2013 to 2017 of patient data collected at sites in 2012 to 2016, respectively). All enrolled patients exposed to ivacaftor (Ivacaftor Cohort) and matched comparators (Comparator Cohort) will be included in the study analyses at each yearly report. As a reference, a Historical Cohort (patient data from 2008) will be included in the study analyses at the first yearly report.Data analyses will be performed by the CF Trust and CF Foundation to support the study objectives. The results of the annual analyses will be reported by Vertex in the study report.The primary objectives of this study are to evaluate long-term safety, pregnancy outcomes, drug utilisation, and CF disease progression in patients treated with ivacaftor. Descriptive statistics will be presented for all endpoints.

Documents

Study results

Long-term Safety Study Results 13July2018

Study publications

Bessonova L, Volkova N, Higgins M, Bengtsson L, Tian S, Simard C, Konstan MW, S…