Clinical Trials Register

Summary
EudraCT Number:	2020-000769-18
Sponsor's Protocol Code Number:	EFC16295
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-05-24
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-000769-18

A.3

Full title of the trial

A Phase 3 open-label, multicenter study of the safety, efficacy, and pharmacokinetics of intravenous recombinant coagulation Factor VIII Fc-von Willebrand Factor-XTEN fusion protein (rFVIIIFc-VWF-XTEN; BIVV001) in previously treated pediatric patients <12 years of age with severe hemophilia A

Studio di fase 3, multicentrico, in aperto per valutare la sicurezza, l’efficacia e la farmacocinetica del Fattore VIII della coagulazione ricombinante Fc - fattore di von Willebrand - proteina di fusione XTEN (rFVIIIFc-VWF-XTEN; BIVV001) somministrato per via endovenosa in pazienti pediatrici di < 12 anni di età affetti da emofilia A severa precedentemente trattati

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Safety, efficacy and PK of BIVV001 in pediatric patients with hemophilia A

Sicurezza, efficacia e PK di BIVV001 in pazienti pediatrici affetti da emofilia A

A.3.2

Name or abbreviated title of the trial where available

XTEND-Kids

A.4.1

Sponsor's protocol code number

EFC16295

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1244-0558

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/238/2020

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	BIOVERATIV THERAPEUTICS INC
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bioverativ Therapeutics Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	SANOFI S.r.l
B.5.2	Functional name of contact point	CONTACT POINT
B.5.3	Address:
B.5.3.1	Street Address	VIALE LUIGI BODIO 37/B
B.5.3.2	Town/ city	MILANO
B.5.3.3	Post code	20158
B.5.3.4	Country	Italy
B.5.4	Telephone number	800226343
B.5.5	Fax number	0239394168
B.5.6	E-mail	informazioni.medicoscientifiche@sanofi.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/19/2176
D.3 Description of the IMP
D.3.1	Product name	Fattore VIII della coagulazione ricombinante Fc - fattore di von Willebrand - proteina di fusione XT
D.3.2	Product code	[BIVV001 (rFVIIIFc-VWF-XTEN)]
D.3.4	Pharmaceutical form	Powder for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Fattore VIII della coagulazione ricombinante Fc - fattore di von Willebrand - proteina di fusione XTEN
D.3.9.1	CAS number	2252477-42-0
D.3.9.2	Current sponsor code	BIVV001 (rFVIIIFc-VWF-XTEN)
D.3.9.3	Other descriptive name	RECOMBINANT HUMAN COAGULATION FACTOR VIII FC - VON WILLEBRAND FACTOR - XTEN FUSION PROTEIN
D.3.9.4	EV Substance Code	SUB195807
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/19/2176
D.3 Description of the IMP
D.3.1	Product name	Fattore VIII della coagulazione ricombinante Fc - fattore di von Willebrand - proteina di fusione XT
D.3.2	Product code	[BIVV001 (rFVIIIFc-VWF-XTEN)]
D.3.4	Pharmaceutical form	Powder for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Fattore VIII della coagulazione ricombinante Fc - fattore di von Willebrand - proteina di fusione XTEN
D.3.9.1	CAS number	2252477-42-0
D.3.9.2	Current sponsor code	BIVV001 (rFVIIIFc-VWF-XTEN)
D.3.9.3	Other descriptive name	RECOMBINANT HUMAN COAGULATION FACTOR VIII FC - VON WILLEBRAND FACTOR - XTEN FUSION PROTEIN
D.3.9.4	EV Substance Code	SUB195807
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/19/2176
D.3 Description of the IMP
D.3.1	Product name	Fattore VIII della coagulazione ricombinante Fc - fattore di von Willebrand - proteina di fusione XT
D.3.2	Product code	[BIVV001 (rFVIIIFc-VWF-XTEN)]
D.3.4	Pharmaceutical form	Powder for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Fattore VIII della coagulazione ricombinante Fc - fattore di von Willebrand - proteina di fusione XTEN
D.3.9.1	CAS number	2252477-42-0
D.3.9.2	Current sponsor code	BIVV001 (rFVIIIFc-VWF-XTEN)
D.3.9.3	Other descriptive name	RECOMBINANT HUMAN COAGULATION FACTOR VIII FC - VON WILLEBRAND FACTOR - XTEN FUSION PROTEIN
D.3.9.4	EV Substance Code	SUB195807
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/19/2176
D.3 Description of the IMP
D.3.1	Product name	Fattore VIII della coagulazione ricombinante Fc - fattore di von Willebrand - proteina di fusione XT
D.3.2	Product code	[BIVV001 (rFVIIIFc-VWF-XTEN)]
D.3.4	Pharmaceutical form	Powder for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Recombinant coagulation FVIII Fc – von Willebrand factor – XTEN fusion protein
D.3.9.1	CAS number	2252477-42-0
D.3.9.2	Current sponsor code	BIVV001 (rFVIIIFc-VWF-XTEN)
D.3.9.3	Other descriptive name	RECOMBINANT HUMAN COAGULATION FACTOR VIII FC - VON WILLEBRAND FACTOR - XTEN FUSION PROTEIN
D.3.9.4	EV Substance Code	SUB195807
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Hemophilia A

Emoflia A

E.1.1.1

Medical condition in easily understood language

Hemophilia A

Emoflia A

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10060612
E.1.2	Term	Hemophilia A
E.1.2	System Organ Class	100000004850

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

To evaluate the safety of BIVV001 in previously treated pediatric subjects with hemophilia A.

Valutare la sicurezza di BIVV001 in partecipanti pediatrici con emofilia A precedentemente trattati.

E.2.2

Secondary objectives of the trial

- To evaluate the efficacy of BIVV001 as a prophylaxis treatment
- To evaluate the efficacy of BIVV001 in the treatment of bleeding episodes
- To evaluate BIVV001 consumption for prevention and treatment of bleeding episodes
- To evaluate the effect of BIVV001 prophylaxis on joint health outcomes
- To evaluate the effect of BIVV001 prophylaxis on Quality of Life (QoL) outcomes
- To evaluate the efficacy of BIVV001 for perioperative management
- To evaluate the safety and tolerability of BIVV001 treatment
- To assess the pharmacokinetics (PK) of BIVV001.

Valutare l’efficacia di BIVV001 come trattamento di profilassi
Valutare l’efficacia di BIVV001 nel trattamento degli episodi emorragici
Valutare l’utilizzo di BIVV001 per la prevenzione e il trattamento degli episodi emorragici
Valutare l’effetto della profilassi con BIVV001 sugli esiti per la salute articolare
Valutare l’effetto della profilassi con BIVV001 sugli esiti della qualità della vita (QoL)
Valutare l’efficacia di BIVV001 per la gestione perioperatoria
Valutare la sicurezza e la tollerabilità del trattamento con BIVV001
Valutare la farmacocinetica (PK) di BIVV001.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Participant must be younger than 12 years of age, at the time of signing the informed consent
- Severe hemophilia A defined as <1 IU/dL (<1%) endogenous FVIII as documented either by central laboratory testing at Screening or in historical medical records from a clinical laboratory demonstrating <1% FVIII coagulant activity (FVIII:C) or a documented genotype known to produce severe hemophilia A.
- Previous treatment for hemophilia A (prophylaxis or on-demand) with any recombinant and/or plasma-derived FVIII, or cryoprecipitate for at least 150 EDs for patients aged 6-11 years and above 50 EDs for patients aged <6 years
- Weight above or equal to 10 kg

- I partecipanti devono avere un’età inferiore ai 12 anni al momento della firma del consenso informato
- Emofilia A grave definita come FVIII endogeno < 1 UI/dl (< 1%) documentato dalle analisi del laboratorio centrale allo screening o nelle cartelle cliniche storiche di un laboratorio clinico che dimostrano un’attività coagulante del FVIII (FVIII:C) < 1% o un genotipo documentato che notoriamente produce emofilia A grave.
- Precedente trattamento per l’emofilia A (profilattico o al bisogno) con qualsiasi FVIII ricombinante e/o plasma derivato o con crioprecipitato per almeno 150 ED per i pazienti di età compresa tra i 6 e gli 11 anni e superiore a 50 ED per i pazienti di età inferiore ai 6 anni.
-Peso maggiore o uguale a 10 kg

E.4

Principal exclusion criteria

- History of hypersensitivity or anaphylaxis associated with any FVIII product.
- History of a positive inhibitor (to FVIII) test defined as >/=0.6 BU/mL, or any value greater than or equal to the lower sensitivity cut-off for laboratories with cut-offs for inhibitor detection between 0.7 and 1.0 BU/mL, or clinical signs or symptoms of decreased response to FVIII administrations. Family history of inhibitors will not exclude the participant.
- Positive inhibitor test result, defined as >/=0.6 BU/mL at Screening

- Anamnesi di ipersensibilità o anafilassi associata a qualsiasi prodotto FVIII
- Anamnesi di un test positivo a un inibitore (del FVIII) definito come >/= 0,6 UB/ml o qualsiasi valore maggiore di o uguale al limite inferiore di sensibilità per i laboratori con limiti per il rilevamento degli inibitori compresi tra 0,7 e 1,0 UB/ml oppure segni clinici o sintomi di risposta ridotta alle somministrazioni di FVIII. L’anamnesi familiare di inibitori non escluderà il partecipante.
- Risultato positivo del test dell’inibitore, definito come >/= 0,6 UB/ml allo screening

E.5 End points

E.5.1

Primary end point(s)

Occurrence of inhibitor development.

Sviluppo di inibitori.

E.5.1.1

Timepoint(s) of evaluation of this end point

baseline to 52 weeks.

DAL BASALEELINE A 52 SETTIMANE

E.5.2

Secondary end point(s)

1 - Annualized bleeding rate (ABR)
2 - Annualized bleeding rate (ABR) by type of bleed
3 - Annualized bleeding rate (ABR) by location of bleed
4 - Percentage of participants who maintain FVIII activity above
prespecified levels
5 - Number of injection and dose of BIVV001 to treat a bleeding episode
6 - Percentage of bleeding episodes treated with a single injection of
BIVV001
7 - Assessment of response to BIVV001 treatment of individual bleeding
episodes
8 - Physician's global assessment of the participant's response based on
BIVV001 treatment
9 - Total annualized BIVV001 consumption
10 - Annualized Joint Bleeding Rate (AJBR)
11 - Target joint resolution
12 - Change in Hemophilia Joint Health Score (HJHS) total score and
domain scores
13 - Changes in Haemophilia Quality of Life Questionnaire for Children
(Haemo-QoL) total score
14 - Changes in Haemophilia Quality of Life Questionnaire for Children
(Haemo-QoL) physical health domain scores
15 - Investigators' or Surgeons' assessment of participant's hemostatic
response to BIVV001 treatment
16-- Number of injections and dose to maintain hemostasis during
perioperative period for major surgery
17 - Total BIVV001 consumption during perioperative period for major
surgery
18 - Number of blood component transfusions used during perioperative
period for major surgery
19 - Type of blood component transfusions used during perioperative
period for major surgery
20 - Estimated blood loss during perioperative period for major surgery
21 - Number of participants with occurence of adverse events (AEs) and
serious adverse events (SAEs)
22 - Number of participants with occurrence of embolic and thrombotic
events
23 - PK parameter: Maximum activity (Cmax)
24 - PK parameter: Elimination half-life (t1/2)
25 - PK parameter: Total clearance (CL)
26 - PK parameter: Total clearance at steady state (CLss)
27 - PK parameter:dose-normalized area under the activity-time curve
(DNAUC)
28 - PK parameter: Area under the activity time curve (AUC)
29 - PK parameter: Volume of distribution at steady state (Vss)
30 - PK parameter: Mean residence time (MRT)
31 - PK parameter: Incremental recovery (IR)
32 - PK parameter: Trough activity (Ctrough)
33 - PK parameter: Time above predefined FVIII activity levels.

1. Tasso annualizzato di sanguinamento (ABR)
2. Tasso annualizzato di sanguinamento (ABR) per tipo
3. Tasso annualizzato di sanguinamento (ABR) per sede
4. Percentuale di pazienti che mantengono livelli di attività del FVIII sopra livelli prespecificati
5. Numero di iniezioni e dose di BIVV001 per il trattamento di un episodio emorragico
6. Percentuale di episodi emorragici trattati con un’unica iniezione di BIVV001
7. Valutazione della risposta al trattamento con BIVV001 di singoli episodi emorragici
8. Valutazione globale del medico (PGA) della risposta del paziente al trattamento con BIVV001
9. Utilizzo totale annualizzato di BIVV001
10. Tasso annualizzato di sanguinamento articolare (AJBR)
11. Risoluzione del quadro alle articolazioni bersaglio
12. Variazione nel punteggio totale e nei punteggi di dominio valutati dalla scala Hemophilia Joint Health Score (HJHS)
13. Variazioni nel punteggio totale del questionario Haemophilia Quality of Life Questionnaire for Children (Haemo-QoL)
14. Variazioni del questionario Haemophilia Quality of Life Questionnaire for Children (Haemo-QoL) nel punteggio del dominio della salute fisica
15. Valutazione degli sperimentatori o dei chirurghi della risposta emostatica del paziente al trattamento con BIVV001
16. Numero di iniezioni e dose per mantenere l’emostasi durante il periodo perioperatorio per interventi di chirurgia maggiore
17. Utilizzo totale di BIVV001 durante il periodo perioperatorio per interventi di chirurgia maggiore
18. Numero di trasfusioni di componenti ematici impiegate durante il periodo perioperatorio per interventi di chirurgia maggiore
19. Tipo di trasfusioni di componenti ematici impiegate durante il periodo perioperatorio per interventi di chirurgia maggiore
20. Perdita ematica stimata durante il periodo perioperatorio per interventi di chirurgia maggiore
21. Numero di partecipanti che manifestano Insorgenza di eventi avversi (EA) ed eventi avversi seri (SAE)
22. Numero di partecipanti che manifestano Insorgenza di eventi embolici e trombotici
23. Parametri PK: attività massima (Cmax),
24. Parametri PK: emivita di eliminazione (t1/2)
25. Parametri PK: clearance totale (CL)
26. Parametri PK: clearance totale allo stato stazionario (CLss)
27. Parametri PK: area sotto la curva del tempo di attività normalizzata per dose (DNAUC)
28. Parametri PK: area sotto la curva del tempo di attività (AUC)
29. Parametri PK: volume di distribuzione allo stato stazionario (Vss)
30. Parametri PK: tempo medio di residenza (MRT)
31. Parametri PK: recupero incrementale (IR)
32. Parametri PK: attività di valle (Ctrough)
33. Parametri PK: tempo al di sopra dei livelli di attività predefiniti del FVIII

E.5.2.1

Timepoint(s) of evaluation of this end point

1 to 6, 8 to 10 , 12 to 23, 31, 32 : Baseline to 52 weeks
7 : 52 weeks
11 : At week 52
24 to 30, 33: Baseline (day 1).

DA 1 A 6, DA 8 A 10 , DA12 A 23, 31, 32 : DAL BASALE A 52 SETTIMANE
7 : 52 SETTIMANE
11 : ALLA SETTIMANA 52
DA 24 A 30, 33: AL BASALE (GIORNO 1)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Canada

Taiwan

Turkey

United States

Belgium

France

Germany

Hungary

Ireland

Italy

Netherlands

Spain

Sweden

Switzerland

United Kingdom

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

End of Study will occur when both of the following criteria have been met:
• At least 50 participants (25 subjects <6 years of age and 25 subjects 6 to <12 years of age) have reached 50 exposure days (EDs) and have completed a valid inhibitor test after the 50th ED.
• 24 participants (12 subjects <6 years of age and 12 subjects 6 to <12 years of age) in the PK subgroup have completed the BIVV001 PK profile with adequate estimate of terminal t1/2.

La fine dello studio si verificherà quando entrambi i seguenti criteri saranno stati soddisfatti:
• Almeno 50 partecipanti (25 soggetti <6 anni di età e 25 soggetti da 6 a <12 anni di età) avranno raggiunto i 50 giorni di esposizione (ED) e avranno completato un valido test inibitore dopo il 50esimo ED.
• 24 partecipanti (12 soggetti <6 anni di età e 12 soggetti da 6 a <12 anni di età) nel sottogruppo PK avranno completato il profilo PK BIVV001 con una stima adeguata del t1 / 2 terminale.

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

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

paediatric population

popolazione pediatrica

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Enrollment in a planned open-label extension study will be offered to participants after completion of this study.

L'arruolamento in uno studio in aperto di estensione pianificato verrà offerto ai partecipanti che completano lo studio

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-11-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-01-12

P. End of Trial
P.	End of Trial Status	Ongoing

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