E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 1 diabetes mellitus |
Diabete mellito di tipo 1 |
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E.1.1.1 | Medical condition in easily understood language |
Type 1 diabetes mellitus |
Diabete mellito di tipo 1 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition 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 compare the efficacy of HOE901-U300 to Lantus in terms of glycated hemoglobin (HbA1c) |
Confrontare l'efficacia di insulina glargine (HOE901-U300) a Lantus, in termini di variazioni dell'emoglobina glicata (HbA1c) |
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E.2.2 | Secondary objectives of the trial |
-To compare HOE901-U300 and Lantus in terms of:
-Percentage of patients reaching target HbA1c and fasting plasma glucose (FPG).
-To assess the safety of HOE901-U300 including analysis of events of hypoglycemia, events of hyperglycemia with ketosis, and development of anti-insulin-antibodies. |
Confrontare HOE901-U300 e Lantus in termini di:
• Percentuale di pazienti che raggiungono il target di HbA1c e glicemia plasmatica a digiuno (FPG)
• Verifica della sicurezza di HOE901-U300 incluse analisi degli eventi ipoglicemici, degli eventi iperglicemici con chetosi e sviluppo di anticorpi anti-insulina
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Children and adolescents with type 1 diabetes mellitus (T1DM) for at least 1 year confirmed by typical symptoms at diagnosis and/or by antibody testing (presence of anti-GAD [glutamic acid decarboxylase] or anti-IA2 [islet antigen 2/tyrosine phosphatase] or anti-islet cell antibodies) and/or clinical features (eg, history of ketoacidosis).
-Signed written informed consent obtained from parent(s)/legal guardian and written or oral assent obtained from patient. |
• Bambini e adolescenti con T1DM da almeno 1 anno, confermato mediante sintomi tipici alla diagnosi e/o mediante test anticorpali anti-GAD [acido glutammico decarbossilasi] o anti-IA2 [antigene insulinico 2/ tirosina fosfatasi] o anticorpi anti-cellule insulari e/o caratteristiche cliniche (ad es. storia di chetoacidosi);
• Consenso informato scritto firmato dal genitore/dai genitori/dal tutore legale e assenso scritto del paziente
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E.4 | Principal exclusion criteria |
-Age <6 years and ≥18 years.
-Less than 1 year on insulin treatment prior to screening visit.
-Less than 6 months on basal plus mealtime insulin and self-monitoring of blood glucose prior to screening visit.
-Patients using premix insulins in the last 3 months before screening visit or patients using human regular insulin as mealtime insulin in the last 3 months before screening visit.
-Use of an insulin pump in the last 6 months before screening visit or plans to switch to pump within the next 6 months after screening visit.
-No willingness to inject insulin glargine (Lantus or HOE901 [U300]) once daily.
-HbA1c <7.5% or >10% at screening.
-Initiation of any glucose-lowering medications in the last 3 months before screening visit.
-Hospitalization or care in the emergency ward for diabetic ketoacidosis or history of severe hypoglycemia (as defined by need for glucagon or IV glucose) and accompanied by seizure and/or unconsciousness and/or coma in the last 3 months prior to screening visit.
-Postmenarchal girls not protected by highly-effective method(s) of birth control and/or who are unwilling or unable to be tested for pregnancy. Abstinence from sexual intercourse will be considered as an acceptable form of birth control.
-Pregnant or breast-feeding adolescents, or adolescents who intend to become pregnant during the study period, or who are at risk of getting pregnant due to any psychosocial reason during the study period. |
• Età <6 anni e ≥18 anni;
• Meno di 1 anno di terapia insulinica prima della visita di screening;
• Meno di 6 mesi di insulina basale più prandiale e automonitoraggio della glicemia prima della visita di screening;
• Pazienti che hanno utilizzato insuline premiscelate nei 3 mesi precedenti la visita di screening o pazienti che hanno usato insulina umana regolare come insulina prandiale nei 3 mesi precedenti la visita di screening;
• Uso di pompa insulinica nei 6 mesi precedenti la visita di screening o intenzione di passare ad una pompa entro 6 mesi dalla visita di screening;
• Mancata volontà di praticarsi/farsi praticare le iniezioni di insulina glargine (Lantus o HOE901-U300) una volta al giorno;
• HbA1c <7.5% o >10% allo screening;
• Inizio di terapia antiglicemica nei 3 mesi precedenti la visita di screening;
• Ricovero o trattamento in pronto soccorso a causa di chetoacidosi diabetica o anamnesi di ipoglicemia grave (definita dalla necessità di assunzione di glucagone o di somministrazione in vena di glucosio), accompagnata da crisi e/o incoscienza e/o coma nei 3 mesi precedenti la visita di screening;
• Ragazze post-menarca non protette da un metodo/da metodi di controllo delle nascite altamente efficace/efficaci che rifiutano o non sono in grado di sottoporsi a test di gravidanza. L'astinenza da rapporti sessuali sarà considerata una forma accettabile di controllo delle nascite;
• Adolescenti gravide o che allattano o che prevedono una gravidanza durante il periodo di studio o che sono a rischio di gravidanza a causa di motivi psicosociali durante il periodo dello studio.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in HbA1c |
Variazione dal basale dell’ HbA1c |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline; Week 26 |
Basale, settimana 26 |
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E.5.2 | Secondary end point(s) |
1- Percentage of patients with HbA1c values of <7.5% without any episode of severe and/or documented (SMPG <54 mg/dL; 3.0 mmol/L) symptomatic hypoglycemia during the last 3 months of the main 6-month on-treatment period
2- Change from baseline in FPG
3- Percentage of patients with FPG of ≤130 mg/dL (7.2 mmol/L) without any episode of severe and/or documented (SMPG ≤54 mg/dL; 3.0 mmol/L) symptomatic hypoglycemia during the last 3 months of the main 6-month
4- Change from baseline in 24-hour mean plasma glucose based on 8-point self-monitored plasma glucose (SMPG) profiles
5- Change from baseline in variability of 24-hour mean plasma glucose based on 8-point SMPG profiles
6- Number (%) of patients with hypoglycemia
7- Number (%) of patients with hyperglycemia with ketosis
8- Number (%) of patients with adverse events |
1. Percentuale di pazienti con valori HbA1c <7.5% senza alcun episodio di ipoglicemia sintomatica grave e/o documentata (SMPG <54 mg/dl; 3.0 mmol/l) negli ultimi 3 mesi del periodo principale di randomizzazione di 6 mesi;
2. Variazione della FPG dal basale;
3. Percentuale di pazienti con glicemia plasmatica a digiuno (FPG) ≤130 mg/dl (7.2 mmol/l) senza alcun episodio di ipoglicemia sintomatica grave e/o documentata (SMPG <54 mg/dl; 3.0 mmol/l) negli ultimi 3 mesi del periodo principale di randomizzazione di 6 mesi;
4. Variazione dal basale della glicemia plasmatica media nelle 24 ore sulla base di profili SMPG a 8 punti;
5. Variazione dal basale della variabilità della glicemia plasmatica media nelle 24 ore sulla base di profili SMPG a 8 punti;
6. Numero (%) di pazienti con ipoglicemia;
7. Numero (%) di pazienti con iperglicemia con chetosi;
8. Numero (%) di pazienti con eventi avversi |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1- Week 26
2- Baseline; Week 26
3- Week 26
4- Baseline; Week 26
5- Baseline; Week 26
6- Up to Month 12
7- Up to Month 12
8- Up to Month 12 |
1. Settimana 26;
2. Basale, settimana 26
3. Settimana 26
4. Basale, settimana 26
5. Basale, settimana 26
6. Fino al mese 12
7. Fino al mese 12
8. Fino al mese 12 |
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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 | No |
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) | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 | No |
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 |
Argentina |
Brazil |
Canada |
Chile |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Italy |
Japan |
Latvia |
Mexico |
Poland |
Romania |
Russian Federation |
Spain |
United Kingdom |
United States |
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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 | 26 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 26 |