E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objective is to investigate whether a further gain in efficacy of oral Ivacaftor treatment can be reached by co-supplementation of genistein, as suggested by their highly synergistic action in intestinal organoids. |
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E.2.2 | Secondary objectives of the trial |
1: to evaluate the correlations between individual Ivacaftor genistein induced CFTR function in vitro (organoid-based measurements) and the in vivo treatment effect. 2: to evaluate the correlation between serum levels of Ivacaftor and genistein and the in vivo treatment effect.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• CFTR genotype associated with residual CFTR function; • Already had a rectal biopsy to produce an organoid; • Use of Ivacaftor; • Male and female patients, aged 6 years or older on the date of informed consent; • Signed informed consent form (IC).
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E.4 | Principal exclusion criteria |
• Use of genistein or curcumin at start or within four weeks prior to start of the study; • Severe acute exacerbation or pulmonary infection during last four weeks (needing intravenous treatment and/or systemic corticosteroids);
• (History of) hypothyroidism; • Women who are trying to become pregnant or are pregnant or breastfeeding; • Women with estrogen receptor-positive tumors; • Postmenopausal women on tamoxifen therapy for estrogen-responsive breast cancer; • Participation in another drug-investigating clinical study at the start or within four weeks prior to the start; • Inability to follow instructions of the investigator.
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E.5 End points |
E.5.1 | Primary end point(s) |
The main study parameter is pulmonary function (%FEV1) measured before and after the use of genistein and before and after the use of placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary endpoints to evaluate in vivo effect:
• Sweat chloride concentration (SCC), before and after the use of genistein and placebo; • Airway resistance (Rint and bodybox), before and after the use of genistein and placebo; • BMI (=weight (in Kg)/Length2 (in cm)) before and after the use of genistein and placebo; • Quality of life (measured with CFQ-questionnaire) before and after the use of genistein and placebo; • Elastase measurements in the feces before and after the use of genistein and placebo; • The CFTR stimulating ability of the concentration of genistein in the patient’s blood samples, examined by in vitro testing (in the organoid model). We will also determine the plasma levels of genistein;
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |