NA

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2018-002624-16-FR
• Date of registration: 21/11/2018
• Prospective Registration: Yes
• Primary sponsor: ASSISTANC-PUBLIQUE-HOPITAUX DE PARIS (AP-HP)
• Public title: NA
• Scientific title: Validation of respiratory epithelial functional assessment to predict clinical efficacy of Orkambi®. Pathway to personalized therapy in Cystic Fibrosis PREDICT-CF - PREDICT-CF
• Target sample size: 104
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-002624-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Prospective cohort study If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

France

Contacts

• Name: DRCI Hôpital Saint-Louis
• Affiliation: ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (AP-HP)

• Name: DRCI Hôpital Saint-Louis
• Affiliation: ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (AP-HP)

Key inclusion & exclusion criteria

Inclusion criteria:
- Homozygous F508del patient aged 12 years or older
- Patient with an indication for Orkambi® treatment according to the marketing authorization application
- Patient never received Orkambi® in the past
- 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


Are the trial subjects under 18? yes
Number of subjects for this age range: 52
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

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




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Homozygous F508del patient aged 12 years or older
MedDRA version: 20.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Trade Name: Orkambi®
Lumacaflor/Ivacaflor.
CAS lumacaflor : 936727-05-8
CAS ivacaflor : 873054-44-5
Product Name: Orkambi®
Pharmaceutical Form: Tablet

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: after 24 weeks of treatment.

Secondary Objective: 1) to assess the predictive value of the test for improvement of the absolute change in the Z-score of the predicted FEV1 from baseline to week 24 of Orkambi®
2) to assess the predictive value of the test for improvement of the absolute change in the percentage / Z-score of predicted FEV1 from baseline to week 48 of Orkambi®
3) to assess the predictive value of the test for the other parameters of the lung function response (Forced Vital Capacity, Residual Functional Capacity) to Orkambi® at week 24 and 48
4) to assess the predictive value of the test for the Lung Clearance Index response to Orkambi® at week 48
5) to assess the predictive value of the test for the nutritional response to Orkambi® at week 24 and 48
6)7)8)9)10)11) cf protocol

Main Objective: To investigate the predictive value for improvement of percentage of predicted FEV1 at 24 weeks of treatment with Orkambi® of a test quantifying in vitro the correction of CFTR activity, as assessed by the change in cyclic AMP (cAMP) dependant Chloride (Cl-) secretion in patient derived HNE culture after Lumacaftor/Ivacaftor 48 hrs incubation.

Primary end point(s): Absolute change in the percentage of predicted forced expiratory volume in 1 second (%FEV1) from baseline to week 24 of Orkambi®.
The response to Orkambi® is defined by an absolute change = 10 % after 24 weeks of treatment.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: to week 24 or to week 48 or to week24 and week 48

Secondary end point(s): 1) Absolute change in the Z-score of forced expiratory volume in 1 second (FEV1) from baseline to week 24
2) Absolute change in percent predicted/Z-score of forced expiratory volume in 1 second (FEV1) from baseline through week 48
3) Absolute change in percent predicted of forced vital capacity (%FVC) and Functional Residual Capacity (%RFC) from baseline through week 24 and 48
4) Absolute change in lung clearance index 2.5 (LCI2.5) from baseline through Week 48
5) Absolute change in height and weight-for-age-z-score from baseline to week 24 and 48
6) Absolute change in CFU of sputum microorganisms from baseline to week 24 and 48
7) Number of exacerbations to week 48 in comparison to the year previous treatment with Orkambi®
8)9)10)11) cf protocol
The response to Orkambi® will also be studied in secondary endpoint as an absolute change in the percentage of FEV1 = 5 % after 24 and 48 weeks of treatment.

Secondary ID(s)

P170907J

Source(s) of Monetary Support

DGOS