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Validation of Respiratory Epithelial Functional Assessment to Predict Clinical Efficacy of Orkambi®. (PREDICT-CF)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03894657
Recruitment Status : Recruiting
First Posted : March 28, 2019
Last Update Posted : July 9, 2020
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:
The purpose of the study is to investigate whether the correction of CFTR function by Lumacaftor/Ivacaftor in a patient-derived primary nasal cell model is a surrogate biomarker for respiratory improvement in Orkambi® treated patients.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Homozygous F508del Mutation Diagnostic Test: Nasal brushing Other: Sputum sample Other: blood sample Drug: Orkambi Not Applicable

Detailed Description:

Orkambi® is a combination of Ivacaftor (a CFTR channel potentiator) and Lumacaftor (a corrector partially rescuing the traffic of mutated CFTR). This treatment is now marketed in France for patients homozygotes for the mutation p.Phe508del, aged 12 and above. Systematic use of this product is a concern due to the lack of predictive markers of efficacy, the highly variable respiratory improvement in patients and potential serious side effects.

The purpose of this study is to investigate the predictive value for improvement of the respiratory function after 24 weeks of Orkambi treatment of an in vitro test. This test quantifies the correction of CFTR activity as assessed by the change of cyclic AMP (cAMP) dependant chloride (Cl-) secretion in patient derived Human Nasal Epithelial (HNE) derived primary culture after Lumacaftor/Ivacaftor 48 hours incubation.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 104 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Validation of Respiratory Epithelial Functional Assessment to Predict Clinical Efficacy of Orkambi®. Pathway to Personalized Therapy in Cystic Fibrosis
Actual Study Start Date : December 18, 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : February 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis


Intervention Details:
  • Diagnostic Test: Nasal brushing
    Nasal scrapping at visit V0
  • Other: Sputum sample

    Visit V0 : 1 Aliquot for Sputum biobank

    Visit V1 : 2 Aliquots

    • for Sputum biobank
    • for pharmacokinetic (PK) study

    Visit V2 : 2 Aliquots

    • for Sputum biobank
    • for pharmacokinetic (PK) study
  • Other: blood sample

    Visit V0 : Additional 14 mL

    • 5 mL in ethylenediaminetetraacetic acid (EDTA) tube for DNA Analysis
    • 3 mL in Dry tube for Serum biobank
    • 6 mL in acid citrate dextrose (ACD) tube for peripheral blood mononuclear cell (PBMC) biobank

    Visit V1 : Additional 9 mL

    • 2x3 mL in dry tube for pharmacokinetic (PK) study
    • 3 mL in Dry tube for Serum biobank

    Visit V2 : Additional 6 mL

    • 3 mL in dry tube for pharmacokinetic (PK) study
    • 3 mL in Dry tube for Serum biobank
  • Drug: Orkambi

    Study the predictive value for improvement of the respiratory function after 24 weeks of Orkambi treatment.

    Orkambi treatment is part of usual care.



Primary Outcome Measures :
  1. Percentage of FEV1 [ Time Frame: Baseline, Week 24 ]
    Absolute change in the percentage of predicted forced expiratory volume in 1 second (%FEV1) from baseline to week 24 of Orkambi®


Secondary Outcome Measures :
  1. Z-score of FEV1 [ Time Frame: Baseline, Week 24, week 48 ]
    Absolute change in the Z-score of forced expiratory volume in 1 second (FEV1) from baseline to week 24 and to week 48

  2. Percentage of FEV1 [ Time Frame: Week 48 ]
    Absolute change in the percentage of predicted forced expiratory volume in 1 second (FEV1) from baseline through week 48

  3. % of FVC [ Time Frame: Baseline, Week 24 and week 48 ]
    Absolute change in percent predicted of forced vital capacity (%FVC) from baseline through week 24 and 48

  4. % of RFC [ Time Frame: Baseline, Week 24 and week 48 ]
    Absolute change in percent predicted of Functional Residual Capacity (%RFC) from baseline through week 24 and 48

  5. Lung clearance index [ Time Frame: Baseline, Week 48 ]
    Absolute change in lung clearance index 2.5 (LCI2.5) from baseline through Week 48

  6. Height [ Time Frame: Baseline, Week 24 and week 48 ]
    Absolute change in height-for-age-z-score from baseline to week 24 and 48

  7. Weight [ Time Frame: Baseline, Week 24 and week 48 ]
    Absolute change in weight-for-age-z-score from baseline to week 24 and 48

  8. colony forming unit (CFU) [ Time Frame: Baseline, Week 24 and week 48 ]
    Absolute change in colony forming unit (CFU) of sputum microorganisms from baseline to week 24 and 48

  9. Number of exacerbations [ Time Frame: Baseline, Week 48 ]
    Number of exacerbations to week 48 in comparison to the year previous treatment with Orkambi®

  10. Sweat Cl- [ Time Frame: Baseline, Week 48 ]
    Absolute change in sweat Cl- from baseline to week 48

  11. Level in Forskolin/IBMXdependant Short Circuit Current [ Time Frame: Baseline ]
    Level in Forskolin/IBMXdependant Short Circuit Current change in patient nasal epithelial (HNE) cells incubated with Lumacaftor/Ivacaftor

  12. percentage of cells displaying apical staining [ Time Frame: baseline ]
    Correction of CFTR expression at the apical membrane in HNE cells incubated with Lumacaftor/Ivacaftor, assessed by the percentage of cells displaying apical staining.

  13. Area under the curve (AUC) of Lumacaftor/Ivacaftor [ Time Frame: Week 24, week 48 ]
    Pharmacokinetic parameters of Lumacaftor, M28-lumacaftor, Ivacaftor, M1-ivacaftor, and M6-ivacaftor

  14. Drug concentrations of Lumacaftor/Ivacaftor [ Time Frame: Week 24, week 48 ]
    Pharmacokinetic parameters of Lumacaftor, M28-lumacaftor, Ivacaftor, M1-ivacaftor, and M6-ivacaftor



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   5 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Homozygous F508del patient aged 5 years or older
  • Patient with an indication for Orkambi® treatment according to the marketing authorization application
  • Patient never received Orkambi® in the past
  • Patient able to perform FEV1
  • Signed Informed consent form by the patient (if aged ≥ 18 years), or by parents / legal guardian and patient's agreement (if aged < 18 years) Patient affiliated to the health insurance system

Exclusion Criteria:

  • Homozygous F508del patients who do not meet the treatment indications according to the marketing authorization application
  • Patients refusing Orkambi®
  • CF patients not homozygous for the p.Phe508del mutation
  • Active smoker
  • Severe nasal mucosa disrepair
  • Contraindications to xylocaine anesthesia,
  • Participation with another interventional study with drug

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): NCT03894657


Contacts
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Contact: ISABELLE SERMET, PhD +33 1 44 49 48 87 isabelle.sermet@aphp.fr
Contact: Laure CHOUPEAUX, MASTER +33 1 44 38 17 11 laure.choupeaux@aphp.fr

Locations
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France
Hôpital Necker-Enfants Malades Recruiting
Paris, ILE DE France, France, 75015
Contact: ISABELLE SERMET, PhD    : +33 1 44 49 48 87    isabelle.sermet@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: ISABELLE SERMET, PhD Hospital Necker Enfants Malades
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03894657    
Other Study ID Numbers: P170907J
2018-002624-16 ( EudraCT Number )
First Posted: March 28, 2019    Key Record Dates
Last Update Posted: July 9, 2020
Last Verified: July 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
CYSTIC FIBROSIS
ORKAMBI
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