Phase II clinical study for the therapy of cystic fibrosis patients with a specific mutation

• Register: EUCTR
• Last refreshed on: 18 January 2016
• Main ID: EUCTR2013-001258-82-IT
• Date of registration: 29/07/2013
• Prospective Registration: Yes
• Primary sponsor: European Institute for Cystic Fibrosis Research (IERFC)
• Public title: Phase II clinical study for the therapy of cystic fibrosis patients with a specific mutation
• Scientific title: A phase II pilot clinical study of experimental research to evaluate the functional rescue of CFTR protein through proteostasis regulators - Proteostasis regulators effect in cystic fibrosis therapy
• Date of first enrolment: 12/09/2013
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001258-82
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes 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: yes Other specify the comparator: no treatment Number of treatment arms in the trial: 2

Countries of recruitment

Italy

Contacts

• Name: Dept. of Translational Medicine
• Affiliation: AOU Federico II, Clinical Department of Pediatrics

• Name: Dept. of Translational Medicine
• Affiliation: AOU Federico II, Clinical Department of Pediatrics

Key inclusion & exclusion criteria

Inclusion criteria:
- Diagnosis of cystic fibrosis by sweat test with chloride level=60 mEq/l and confirmed by genetic analysis in order to search cystic fibrosis F508del-CFTR homozigotic mutation or F508del-CFTR combined mutations of class I and II
- males or females aged at least 6 years old.
- fertile females should accept a contraceptive method.
- FEV1 =40% as compared to expected value for age and sex.
- At least 2 sweat tests within the 3 months before Meeting 1 to
establish the interindividual variation of chloride level in the sweat.
- Informed agreement
- All subjects must be able to understand the aim of the study
Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Treatment with glucocorticoids per os or via inhalationat Meeting 1 or within 4 weeks before meeting 1.
- Treatment with oxygen, over day or over night.
- Other experimental drugs.
- Hypersensitivity (local or general) to cysteamine or penicillamine.
- Modifications in the therapy with macrolides, ant-asmatic, mucolytic
drugs, Dornase alfa, and/or FANS, DHA within 28 days before Meeting 1.

However, ita can be accepted the use of some drugs (for example FANS).
- Lung/hepatic/other organ transplantation.
- Kidney or hepatic alterations at Meeting 1:
-AST, ALT > 5 fold normal value . -
Creatinine > 2 fold normal value (ULN).
- Pregnancy
- Nursing.
- No contraceptive method.
- Neurologic and psychiatric pathologies that, on the basis of the Researcher
experience, could interfere with protocol


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

Health Condition(s) or Problem(s) studied

Cystic fibrosis patients with F508del-CFTR in homozygous or compound heterozygous with Class I or II mutations

Therapeutic area: Body processes [G] - Genetic Phenomena [G05]

Intervention(s)

Trade Name: Cystagon
Product Name: Cysteamine bitartrate (Cystagon)
Product Code: EMEA/H/C/000125
Pharmaceutical Form: Capsule

Primary Outcome(s)

Main Objective: To investigate the effectiveness in the functional rescue of CFTR protein and the safety in the use of proteostasis regulator (cysteamine bitartrate) in association with a flavonoid (epigallocatechine gallate)
with the aim to strenghten the beneficial effects of cysteamine on the
F508del-CFTR protein at the plasma membrane level, in cystic fibrosis
patients with F508del-CFTR in homozygous or compound heterozygous with Class I or II mutations aged at least 6 years old. The study has been temporally extended in order to asses the therapeutic efficacy as well as tolerability of cysteamine bitartrate in patients either patient homozygotes or heterozigotes for F508del-CFTR

Primary end point(s): Sweat test: reduction of chloride of at leastl 15% as compared to the same
patient at the beginning of the study.
Brushing of the nose: experiments will be performed to a) evaluate the
chloride channel activity of CFTR by SPQ technique; b) the expression of
pro-inflammatory cytokines (TNFalpha, IL-8) by Polymerase Chain
Reaction (PCR) as compared to the same patient at the beginning of the
study.

Timepoint(s) of evaluation of this end point: After 4,8, 12, 20, 28, 36, 44 weeks

Secondary Objective: not applyable

Secondary Outcome(s)

Secondary end point(s): In the sputum it will be evaluated a) the number of pro-inflammatory
cells; b) IL-8 and neutrophilic elastase levels as compared to the same
patient at the beginning of the study.

Timepoint(s) of evaluation of this end point: After 4, 8, 12, 20, 28, 36, 44 weeks from the beginning of the study

Secondary ID(s)

CFTRcysta1

Source(s) of Monetary Support

European Institute for Cystic Fibrosis Research (IERFC)