A B2-agonist as a CFTR activator in CF - Part 2

• Register: EUCTR
• Last refreshed on: 22 May 2017
• Main ID: EUCTR2015-001317-28-NL
• Date of registration: 19/05/2015
• Prospective Registration: Yes
• Primary sponsor: UMC Utrecht
• Public title: A B2-agonist as a CFTR activator in CF - Part 2
• Scientific title: A B2-agonist as a CFTR activator in CF - Part 2 - ABBA 2
• Date of first enrolment: 30/07/2015
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001317-28
• 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: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Netherlands

Contacts

• Name: Gitte Berkers
• Affiliation: UMC Utrecht

• Name: Gitte Berkers
• Affiliation: UMC Utrecht

Key inclusion & exclusion criteria

Inclusion criteria:
- CFTR genotype compound/A455E or compound/R117H
- Already had a rectal biopsy to produce an organoid
- Males and females, aged 18 years or older on the date of informed consent
- Signed informed consent form (ICF)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Severe acute exacerbation or pulmonary infection during last four weeks (needing intravenous treatment and/or systemic corticosteroids)
- Known cardiovascular medical history like cardiac failure, arrhythmias, ischemic cardiac disease, long QT interval syndrome and hypertension
- Known hyperthyroidism, thyrotoxicosis, galactose intolerance, lactase deficiency or glucose-galactose malabsorption
- Haemoglobin A1C (HBA1C) > 45 mmol/mol
- Use of oral B2-agonist one week prior to the start of the study (V1)
- Use of: heart glycoside, high dose sympathomimetics, theophylline, thiazide diuretics or non-selective beta-blockers
- Pregnancy or breastfeeding
- Participation in another drug-investigating clinical study at the start
- Inability to follow instructions of the investigator



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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Cystic fibrosis

Intervention(s)

Trade Name: Salbutamol
Pharmaceutical Form: Tablet

Primary Outcome(s)

Main Objective: to evaluate the clinical effect of a long term treatment (8 weeks) with oral B2-agonists in CF patients with residual CFTR function

Secondary Objective: 1. Evaluate the correlations between individual B2-agonist-induced CFTR function in vitro (organoid-based measurements) and the long term clinical treatment effect (eg. lung function and airway resistance).
2. Assess the effect of the salbutamol concentration in the blood on CFTR function in the background of patient specific parameters. We will do this by examining the CFTR-stimulating potential of the patients’ blood in vitro (in the organoid model).

Timepoint(s) of evaluation of this end point: Before and after treatment with salbutamol

Primary end point(s): Pulmonary function before and after treatment with salbutamol

Secondary Outcome(s)

Secondary end point(s): • Fraction exhaled Nitric Oxide (FeNO) and Nasal Nitric Oxide (nNO);
• BMI (=weight (in Kg)/Length2 (in cm));
• Quality of life (measured with Cystic Fibrosis Questionnaire (CFQ));
• Bile salt measurements in plasma and the feces;
• Elastase measurements in the feces;
• SCC measurements;
• Upper and lower airway microbial profiles (microbiome) (conventional culturing, high throughout pyrosequencing (16S rRNA) for bacterial diversity and relative abundance).
• Correlation between individual salbutamol induced CFTR function in vitro (organoid-based measurements) and the in vivo treatment effect;
• The CFTR stimulating ability of the concentration of salbutamol in the patient’s blood samples, examined by in vitro testing (in the organoid model);

Timepoint(s) of evaluation of this end point: Before and after treatment with salbutamol

Secondary ID(s)

ABBA-2

Source(s) of Monetary Support

NCFS

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