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Trial record 37 of 38 for:    Recruiting, Not yet recruiting, Available Studies | "Sweat"

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

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ClinicalTrials.gov Identifier: NCT02807415
Recruitment Status : Recruiting
First Posted : June 21, 2016
Last Update Posted : February 27, 2018
Sponsor:
Collaborators:
Heidelberg University
University of Giessen
Information provided by (Responsible Party):
Hannover Medical School

Brief 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.

Condition or disease Intervention/treatment
Cystic Fibrosis Drug: Lumacaftor plus Ivacaftor

  Show Detailed Description

Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Intestinal Current Measurements (ICM) to Evaluate the Activation of Mutant CFTR in Subjects With Cystic Fibrosis Aged 12 Years and Older, Homozygous for the p.Phe508del-CFTR Mutation, Treated With Lumacaftor in Combination With Ivacaftor
Actual Study Start Date : June 1, 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

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


Intervention Details:
  • Drug: Lumacaftor plus Ivacaftor
    Oral treatment with lumacaftor/ivacaftor tablets according to the prescribing information
    Other Name: Orkambi; VX-770; VX-809


Primary Outcome Measures :
  1. ICM Absolute change from baseline of the cumulative chloride secretory ion current response to forskolin/IBMX and carbachol in rectal tissue as a CFTR biomarker [ Time Frame: Measurement at the baseline visit within a 4-week interval prior to the start of oral treatment with lumacaftor and ivacaftor; second measurement at a day 10 - 14 weeks after the initiation of oral treatment with lumacaftor and ivacaftor ]
    ICM will be performed according to the Standard Operating Procedure ICM_EU001, version 2.7 (October 2011) 'Ion Transport in Rectal Biopsies for Diagnosis and Clinical Trials in Cystic Fibrosis of the European Cystic Fibrosis Society (ECFS) Diagnostic Working Group & Clinical Trials Network modified by in-house protocol adjustments at the CF electrophysiology laboratories in Hannover and Heidelberg as described by Graeber et al. (2015) [39]. Electronic files of the tracings will be evaluated on-site and at the CF Electrophysiology Laboratory at the University of Heidelberg.


Secondary Outcome Measures :
  1. Spirometry Absolute change from baseline in percent predicted forced expiratory volume in 1 second (FEV1) [ Time Frame: Measurement at the baseline visit within a 4-week interval prior to the start of oral treatment with lumacaftor and ivacaftor; second measurement at a day 10 - 14 weeks after the initiation of oral treatment with lumacaftor and ivacaftor ]

    Pre-bronchodilator spirometry will be performed using in-house equipment. Pre-bronchodilator spirometry is defined as spirometry testing performed for a subject who has

    • Withheld short-acting bronchodilators or anticholinergic agents for more than 4 hours before the spirometry assessment; and
    • Withheld their long-acting bronchodilator (e.g., salmeterol) more than 12 hours before the spirometry assessment; and
    • Withheld their once-daily, long-acting bronchodilator (e.g., tiotropium bromide) for more than 24 hours before the spirometry assessment.

  2. NPD Absolute change from baseline of the Sermet score of nasal transepithelial potential difference measurements (NPD) as a CFTR biomarker [ Time Frame: Measurement at the baseline visit within a 4-week interval prior to the start of oral treatment with lumacaftor and ivacaftor; second measurement at a day 10 - 14 weeks after the initiation of oral treatment with lumacaftor and ivacaftor ]
    NPD will be performed according to the Standard Operating Procedure NPD_EU001, version 1.7 (March 2013) 'Nasal Potential Difference (NPD) Measurement for Diagnosis and Clinical Trials in Cystic Fibrosis' of the European Cystic Fibrosis Society (ECFS) Diagnostic Working Group & Clinical Trials Network. Electronic files of the tracings will be evaluated on-site and at the CF Electrophysiology Laboratory of Hannover Medical School.

  3. Sweat chloride testing Absolute change from baseline of the chloride concentration in Gibson-Cooke pilocarpine iontophoresis sweat test as a CFTR biomarker [ Time Frame: Measurement at the baseline visit within a 4-week interval prior to the start of oral treatment with lumacaftor and ivacaftor; second measurement at a day 10 - 14 weeks after the initiation of oral treatment with lumacaftor and ivacaftor ]
    The sweat test will be performed according the Clinical and Laboratory Standards Institute guidelines (Clinical and Laboratory Standards Institute: Sweat Testing: Sample Collection and Quantitative Chloride Analysis; Approved Guideline-Third Edition, Volume CLSI document C34-A3. Wayne, PA, USA: Clinical and Laboratory Standards Institute; 2009). After stimulation of sweat production by pilocarpine iontophoresis and collection of sweat (Macroduct®; Wescor Inc., Logan, NV, USA), the sweat chloride concentration is determined in-house by original titration with a chloridometer.


Other Outcome Measures:
  1. Drug testing Plasma concentrations of lumacaftor, ivacaftor, and their metabolites [ Time Frame: Measurement at the baseline visit within a 4-week interval prior to the start of oral treatment with lumacaftor and ivacaftor; second measurement at a day 10 - 14 weeks after the initiation of oral treatment with lumacaftor and ivacaftor ]
    Whole blood samples will be collected. Plasma will be assayed by HPLC.

  2. Safety Issues assessed by Liver-related events, respiratory events and elevation of blood creatine phosphokinase [ Time Frame: Measurement at the baseline visit within a 4-week interval prior to the start of oral treatment with lumacaftor and ivacaftor; second measurement at a day 10 - 14 weeks after the initiation of oral treatment with lumacaftor and ivacaftor ]
    Liver-related events (serum serum aspartate transaminase, serum alanine transaminase, gamma-glutamyl transpeptidase, total bilirubin), respiratory events (chest discomfort, dyspnea, and respiration abnormal) and elevation of blood creatine phosphokinase will be monitored according to the FDA-approved patient labeling and the prescribing information.


Biospecimen Retention:   Samples Without DNA
plasma samples


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Subjects with cystic fibrosis aged 12 years and older, homozygous for the p.Phe508del-CFTR mutation
Criteria

Inclusion Criteria:

  1. p.Phe508del homozygous subjects aged 12 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 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®.

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): NCT02807415


Contacts
Contact: Burkhard Tümmler, MD PhD 00495115322920 tuemmler.burkhard@mh-hannover.de
Contact: Marc Barthold, MD 00495115325719 barthold.marc@mh-hannover.de

Locations
Germany
Justus-Liebig-University Recruiting
Gießen, Germany, 35385
Contact: Lutz Nährlich, MD    004964198557620    lutz.naehrlich@paediat.med.uni-giessen.de   
Contact: Claudia Rückes-Nilges, Dipl-Biol    004964198556945    claudia.rueckes-nilges@paediat.med.uni-giessen.de   
Principal Investigator: Lutz Nährlich, MD         
Sub-Investigator: Stefan Kuhnert, MD         
Hannover Medical School Recruiting
Hannover, Germany, 30625
Contact: Burkhard Tümmler, MD PhD    00495115322920    tuemmler.burkhard@mh-hannover.de   
Contact: Christian Dopfer, MD    00495115326111    dopfer.christian@mh-hannover.de   
Principal Investigator: Burkhard Tümmler, MD PhD         
Sub-Investigator: Christian Dopfer, MD         
University of Heidelberg Recruiting
Heidelberg, Germany, 69120
Contact: Marcus Mall, MD    00496221564502    Marcus.Mall@med.uni-heidelberg.de   
Contact: Simon Gräber, MD    004962215638926    Simon.Graeber@med.uni-heidelberg.de   
Principal Investigator: Marcus Mall, MD         
Sub-Investigator: Simon Gräber, MD         
Sub-Investigator: Susanne Dittrich, MD         
Sponsors and Collaborators
Hannover Medical School
Heidelberg University
University of Giessen
Investigators
Principal Investigator: Burkhard Tümmler, MD PhD Hannover Medical School
Principal Investigator: Marcus Mall, MD Heidelberg University
Principal Investigator: Lutz Nährlich, MD University of Giessen

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hannover Medical School
ClinicalTrials.gov Identifier: NCT02807415     History of Changes
Other Study ID Numbers: 2846-2015 82DZLE12A1
First Posted: June 21, 2016    Key Record Dates
Last Update Posted: February 27, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data will be made available to study participant and parental guide and the physician treating the study participant
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Time Frame: IPD data are made available in a written summary report to the physician treating the study participant within 4 weeks after study day 2
Access Criteria:

access criterion: - the individual study participant gains access to printouts of sweat chloride concentration, NPD and ICM tracings upon request.

- the physician treating the study participant receives a written report for this subject that summarizes the findings of spirometry, sweat chloride concentration, NPD and ICM tracings.


Keywords provided by Hannover Medical School:
cystic fibrosis
CFTR
CFTR modulation
sweat test
intestinal current measurement, ICM
nasal transepithelial potential difference measurement, NPD

Additional relevant MeSH terms:
Fibrosis
Cystic 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