ICM to Evaluate the Activation of p.Phe508del-CFTR by Lumacaftor in Combination With Ivacaftor

• Status: Completed
• Trial end date: 2020-02-10
• Target enrollment: 0
• Participant gender: All

Summary

The academic investigator - initiated trial will evaluate in a postapproval setting whether, and if yes, to what extent and variability, the treatment with lumacaftor in combination with ivacaftor reverses the p.Phe508del CFTR - mediated basic defect in p.Phe508del homozygous subjects with cystic fibrosis under real life conditions.

• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hannover Medical School
• Collaborators: Heidelberg University; University of Giessen
• Treatments: Ivacaftor

Criteria

Inclusion Criteria:

1. p.Phe508del homozygous subjects aged 6 years and older with cystic fibrosis

2. FEV1 ≥ 40% of predicted normal for age, gender and height (Knudson standards) or FEV1 > 35% of predicted normal for age, gender and height at baseline, stable lung function during the preceding three months and no acute upper or lower respiratory infection or pulmonary exacerbation during the preceding four weeks

3. Hematology, serum chemistry, coagulation results at baseline with no clinically significant abnormalities that would interfere with the oral treatment with Orkambi® and with the study assessments, as judged by the investigator

4. Able to understand and comply with protocol requirements, restrictions, and instructions and likely to complete the study as planned, as judged by the investigator

5. Willing to remain on a stable medication regimen and administration of Orkambi® according to the FDA-approved patient labeling and the prescribing information for the duration of study participation -

Exclusion Criteria:

1. History of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering Orkambi®

2. An acute upper or lower respiratory infection or pulmonary exacerbation at baseline

3. Advanced liver disease as documented by sonography

4. Abnormal liver function at baseline, defined as ≥ 3 upper limit of normal in minimum 3 of the following: serum aspartate transaminase, serum alanine transaminase, gamma-glutamyl transpeptidase, or total bilirubin

5. Abnormal blood creatine phosphokinase at baseline

6. Abnormal renal function at baseline, defined as creatinine clearance < 60 mL/min

7. Co-medication with strong Cytochrome P450, Family 3, subfamily A (CYP3A) inhibitors and inducers

8. Non-congenital lens opacities

9. Haemorrhoids (bleeding risk when taking rectal suction biopsies for ICM)

10. History of nasal surgery that removed the respiratory epithelium

11. Topical treatment of nostrils in the 3 days prior to baseline

12. Disturbing nasal aspects of secretions, erythema, crustae, ulcera, edema at baseline

13. Participation in a clinical study involving administration of a CFTR modulator

14. History of solid organ or haematological transplantation

15. History of alcohol, medication, or illicit drug abuse Exclusion criteria 1, 3, 4, 5, 6, 7 and 8 refer to known risk factors for the treatment with Orkambi®.