E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neurological symptoms of Ataxia Telangiectasia |
Sintomi neurologici di atassia teleangectasia |
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E.1.1.1 | Medical condition in easily understood language |
Patients with Ataxia Telangiectasia |
Paziente affetti da atassia teleangectasia |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003594 |
E.1.2 | Term | Ataxia telangiectasia |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
-To monitor and evaluate the long-term safety and tolerability of EDS-EP in AT patients. -To evaluate the long term effect of EDS-EP in treating CNS symptoms as measured by the "Modified" International Cooperative Ataxia Rating Scale (mICARS), and Clinical Global Impression of severity and change (CGI-S/C) |
-Monitorare e valutare la sicurezza e la tollerabilità a lungo termine di EDS-EP nei pazienti con AT. -Valutare l'effetto a lungo termine di EDS-EP nel trattamento dei sintomi del SNC in base alla misurazione sulla scala di valutazione dell'atassia "modificata" dell'International Cooperative (International Cooperative Ataxia Rating Scale, mICARS) e all'impressione clinica globale di gravità e cambiamento (Clinical Global Impression of severity/change, CGI- S/C). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the long-term effect of EDS-EP on health related Quality of Life (QoL; EQ-5D-5L scale). |
-Valutare l'effetto a lungo termine di EDS-EP sulla qualità della vita correlata alla salute (Quality of Life, QoL; scala EQ-5D-5L). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Patient completed the double-blind period in the IEDAT-02-2015 trial and must have completed the final (Visit 15/Month 12) efficacy assessments of IEDAT-02-2015. 2.Patient tolerated the study medication, without any evidence of steroid adverse events, or treatment-related severe/ serious adverse events. 3.Body weight > 15 kg. 4.The patient and his/her parent/caregiver (if below the age of consent), or a legal representative, has provided written informed consent to participate. If consent is provided solely by the caregiver in accordance with local regulations, the patient must provide assent to participate in the study. 5.Patient does not present safety contraindications for continuation of treatment, as determined by the Principal Investigator (PI) according to the procedures described below. Procedure for selecting patients for further treatment: The Principal Investigator will ask all patients who meet the aboverequirements, and determine their interest in continuing to receive treatment with the study medication in a new protocol. The Principal Investigator will then determine the eligibility of the patients on the basis of his/her clinical judgement of patients' status and their safety. |
1. Il paziente ha completato il periodo in doppio cieco nella sperimentazione IEDAT-02-2015 e deve aver completato le valutazioni di efficacia finali (Visita 15/Mese 12) di IEDAT-02-2015. 2. Il paziente ha tollerato il farmaco in studio, senza alcuna evidenza di eventi avversi da steroidi o eventi avversi gravi/gravi correlati al trattamento. 3. Peso corporeo > 15 kg. 4. Il paziente e il suo genitore/caregiver (se inferiore all'età del consenso), o un rappresentante legale, hanno fornito il consenso informato scritto alla partecipazione. Se il consenso viene fornito esclusivamente dal caregiver in conformità con le normative locali, il paziente deve fornire il proprio assenso a partecipare allo studio. 5. Il paziente non presenta controindicazioni di sicurezza per la continuazione del trattamento, come determinato dallo sperimentatore principale (Principal Investigator, PI) secondo le procedure descritte di seguito. Procedura per la selezione dei pazienti per l'ulteriore trattamento in IEDAT-03-2018 • Lo sperimentatore principale chiederà a tutti i pazienti che soddisfano i requisiti di cui sopra e determinerà il loro interesse a continuare a ricevere il trattamento con il farmaco in studio in un nuovo protocollo. Lo sperimentatore principale determinerà quindi l'idoneità dei pazienti sulla base del proprio giudizio clinico sullo stato dei pazienti e sulla loro sicurezza. |
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E.4 | Principal exclusion criteria |
Females that are a. pregnant, or are breast-feeding (for EU countries only); b. of childbearing potential, pregnant, or are breast-feeding (for US and Rest of World countries). Females of childbearing potential using adequate birth control will be eligible. A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. See Section 11.7 Concomitant Medications for adequate methods of birth control. 2.A disability that may prevent the patient from completing all study requirements. 3.Current participation in a clinical study with another investigational drug. Medical History and Current Status 4.CD4+ lymphocytes count <400/mm3 (for patients 6 years of age) or <200/mm3 (for patients >6 years). 5.Current neoplastic disease. 6.Severe impairment of the immunological system. 7.Severe or unstable pulmonary disease. 8.Uncontrolled diabetes. Patients with diabetes that has been stabilized (i.e. no hypoglycemic or hyperglycemic episodes in the past 3 months) will be eligible. 9.Any other severe, unstable, or serious disease or condition that in the Investigator's opinion would put the patient at risk for imminent lifethreatening morbidity, need for hospitalization, or mortality. 10.Eligibility of patients with abnormal laboratory test values will be determined by the Investigator. 11.Confirmed hemoglobinopathies, e.g. hemoglobin C disease, sickle cell anemia, or thalassemia. 12.Moderate or severe renal and/or hepatic impairment. 13.Patients who experienced moderate/ severe steroid side effects, or moderate/ severe adverse events associated with the study medication administered in the IEDAT-02 study. Prior/Concomitant Medication 14.Requires treatment with an oral or parenteral steroid. Treatment with inhaled or intranasal steroids for asthma or allergies, as well as use of topical steroids will be permitted. 15.Requires any other concomitant medication prohibited by the protocol. 16.Use of any drug that is a strong inducer/inhibitor of CYP3A4. |
Principi generali 1. Donne a. in stato di gravidanza o in allattamento (solo per i paesi dell'UE); b. in età fertile, in gravidanza o in allattamento (per Stati Uniti e Paesi del resto del mondo). Saranno ritenute idonee le donne in età fertile che utilizzano un metodo contraccettivo adeguato, come determinato dal loro operatore sanitario di riferimento. 2. Una disabilità che può impedire alla paziente di completare tutti i requisiti dello studio. 3. Partecipazione attuale a uno studio clinico con un altro farmaco sperimentale. Anamnesi medica e stato attuale 4. Conta dei linfociti CD4 + < 400/mm3 (per i pazienti di età pari a 6 anni) o <150/mm3 (per i pazienti > 6 anni). In presenza di infezioni orali, come la candidosi orale, documentate allo screening o ricorrenti secondo la documentazione di anamnesi, il limite aumenta a < 200/mm3 (per i pazienti > 6 anni). 5. Malattia neoplastica in corso. 6. Grave compromissione del sistema immunitario. 7. Malattia polmonare grave o instabile. 8. Diabete non controllato. I pazienti con diabete stabilizzato (cioè nessun episodio ipoglicemico o iperglicemico negli ultimi 3 mesi) saranno ammissibili. 9. Qualsiasi altra malattia o condizione grave, instabile o seria che, secondo l'opinione dello sperimentatore, metterebbe il paziente a rischio di imminente morbilità potenzialmente letale, necessità di ricovero o mortalità. 10. L'ammissibilità dei pazienti con valori anomali degli esami di laboratorio sarà determinata dallo sperimentatore. 11. Emoglobinopatie confermate, ad es. malattia da emoglobina C, anemia falciforme o talassemia. 12. Insufficienza renale e/o epatica moderata o grave. 13. Pazienti che hanno manifestato effetti collaterali da steroidi moderati/gravi o eventi avversi moderati/gravi associati al farmaco in studio somministrato nella sperimentazione IEDAT-02. Farmaci precedenti/concomitanti 14. Necessità di trattamento con uno steroide orale o parenterale. Sarà consentito il trattamento con steroidi per via inalatoria o intranasale per asma o allergie, nonché l'uso di steroidi topici. 15. Necessità di qualsiasi altro farmaco concomitante proibito dal protocollo. 16. Uso di qualsiasi forte induttore/inibitore di CYP3A4. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To monitor and evaluate the long-term safety and tolerability of EDS-EP in AT patients |
Monitorare e valutare la sicurezza e la tollerabilità a lungo termine di EDS-EP nei pazienti con AT. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During the study, long-term efficacy assessments will be performed every 6 months, while safety parameters will be assessed at each monthly visit. |
Durante lo studio, verranno eseguite valutazioni di efficacia a lungo termine ogni 6 mesi, mentre i parametri di sicurezza saranno valutati a ciascuno visita mensile. |
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E.5.2 | Secondary end point(s) |
To evaluate the long-term effect of EDS-EP on health related Quality of Life (QoL; EQ-5D-5L scale). |
Valutare l'effetto a lungo termine di EDS-EP sulla qualità della vita correlata alla salute (Quality of Life, QoL; scala EQ-5D-5L). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Durante lo studio, verranno eseguite valutazioni di efficacia a lungo termine ogni 6 mesi, mentre i parametri di sicurezza saranno valutati a ciascuno visita mensile. |
During the study, long-term efficacy assessments will be performed every 6 months, while safety parameters will be assessed at each monthly visit. |
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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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Studio in aperto |
Open Label |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
India |
Tunisia |
United States |
Belgium |
Germany |
Italy |
Norway |
Poland |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 30 |
E.8.9.2 | In all countries concerned by the trial days | 0 |