Clinical Trials Register

Summary
EudraCT Number:	2016-003681-34
Sponsor's Protocol Code Number:	WIL-27
National Competent Authority:	Bulgarian Drug Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-11-03
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

Bulgarian Drug Agency

A.2

EudraCT number

2016-003681-34

A.3

Full title of the trial

Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Immunogenicity of Wilate in Previously Treated Patients with Severe Hemophilia A

Клинично изпитване за изследване на фармакокинетика, ефикасност,
безопасност и имуногенност на Wilate при предварително лекувани
пациенти с тежка хемофилия А

A.3.1

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

Study to Investigate the product Wilate in Patients with Severe Hemophilia A

Клинично изпитване за изследване на продукт Wilate при пациенти с
тежка хемофилия А

A.4.1

Sponsor's protocol code number

WIL-27

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Octapharma AG
B.1.3.4	Country	Switzerland
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	Octapharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Octapharma AG
B.5.2	Functional name of contact point	Clinical Trial Manager
B.5.3	Address:
B.5.3.1	Street Address	Seidenstrasse 2
B.5.3.2	Town/ city	Lachen
B.5.3.3	Post code	CH-8853
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41554512184
B.5.5	Fax number	+41554512151
B.5.6	E-mail	Irena.Dzhunova@octapharma.ch

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	Yes
D.2.1.1.1	Trade name	Wilate
D.2.1.1.2	Name of the Marketing Authorisation holder	Octapharma (IP) Ltd UK
D.2.1.2	Country which granted the Marketing Authorisation	Bulgaria
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Wilate
D.3.4	Pharmaceutical form	Powder and solvent for solution 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	Wilate
D.3.9.2	Current sponsor code	Wilate
D.3.9.3	Other descriptive name	HUMAN COAGULATION FACTOR VIII, VON WILLEBRAND FACTOR COMPLEX
D.3.9.4	EV Substance Code	SUB78203
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	Yes
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
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	Yes
D.2.1.1.1	Trade name	Wilate
D.2.1.1.2	Name of the Marketing Authorisation holder	Octapharma (IP) Ltd UK
D.2.1.2	Country which granted the Marketing Authorisation	Bulgaria
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Wilate
D.3.4	Pharmaceutical form	Powder and solvent for solution 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	Wilate
D.3.9.2	Current sponsor code	Wilate
D.3.9.3	Other descriptive name	HUMAN COAGULATION FACTOR VIII, VON WILLEBRAND FACTOR COMPLEX
D.3.9.4	EV Substance Code	SUB78203
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	Yes
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
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

Severe hemophilia A (<1% FVIII:C)

Тежка хемофилия А (<1% FVIII:C)

E.1.1.1

Medical condition in easily understood language

Severe hemophilia A

Тежка хемофилия А

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	10060613
E.1.2	Term	Hemophilia A (Factor VIII)
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

The primary objective of this study is to determine the efficacy of Wilate in the prophylactic treatment of previously treated patients (PTP) with severe hemophilia A.

Основната цел на това изпитване е да определи ефикасността на
Wilate при профилактика на вече лекувани пациенти с тежка
хемофилия А

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are to:
• Determine the efficacy of Wilate in the treatment of breakthrough
bleeding episodes (BEs)
• Determine the efficacy of Wilate in surgical prophylaxis
• Calculate the FVIII:C pharmacokinetics (PK) for Wilate at baseline
• Calculate the FVIII:C incremental IVR of Wilate over time (at baseline, and at 3 and 6 months of treatment)
• Assess the association between AB0 blood type and the FVIII:C half-life of Wilate
• Assess the association between the VWF:Ag concentration and the FVIII:C half-life of Wilate
• Assess the safety and tolerability of Wilate
• Assess the immunogenicity of Wilate

Вторичните цели на това изпитване са да:
• Определи ефикасността на Wilate при лечение на епизоди на
пробивно кървене
• Определи ефикасност на Wilate в хирургичната профилактика
• Калкулира FVIII:C фармакокинетика за Wilate на изходно ниво
• Калкулира FVIII:C Частично in vivo възстановяване (IVR) на Wilate
с течение на времето (на изходното ниво и на 3-ти и 6-ти месец от
лечението)
• Оцени връзката между кръвна група AB0 и FVIII:C полуживот на
Wilate
• Оцени връзка между концентрацията на VWF:Ag и FVIII:C
полуживот на Wilate
• Оцени безопасност и поносимост на Wilate
• Оцени имунногеността на Wilate

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Severe hemophilia A (<1% FVIII:C) according to medical history
2. Male patients aged ≥12 years
3. Previous treatment with a FVIII concentrate for at least 150 exposure days (EDs)
4. Immunocompetence (CD4+ count >200/µL)
5. Good documentation of the historical bleeding rate (at least for the 6 months pre-ceding study start)
6. Voluntarily given, fully informed written and signed consent obtained by the pa-tient (or parent/legal guardian in case of adolescents) before any study-related pro-cedures are conducted

1.Тежка хемофилия A (<1% FVIII:C) съгласно анамнеза
2. Пациенти от мъжки пол на възраст ≥12 години
3. Предходно лечение с FVIII концентрат за най-малко 150 дни на
приложение (ДП)
4. Имунокомпетентност (CD4+ брой >200/μL)
5. Надлежно документирана предходна честота на кървене (най-
малко 6 месеца преди началото на изпитването)
6. Доброволно дадено, напълно информирано писмено и подписано
съгласие, получено от пациента (или от родител/законен настойник,
ако е непълнолетно лице) преди провеждане на процедури, свързани
с изпитването

E.4

Principal exclusion criteria

1. Any coagulation disorders other than hemophilia A
2. History of FVIII inhibitor activity (≥0.6 BU) or detectable FVIII inhibitory anti-bodies (≥0.6 BU using the Nijmegen modification of the Bethesda assay) at screening, as determined by the central laboratory
3. Severe liver or kidney diseases (alanine aminotransferase [ALAT] and aspartate transaminase [ASAT] levels >5 times of upper limit of normal, creatinine
>120 µmol/L)
4. Patients receiving or scheduled to receive immunomodulating drugs (other than anti-retroviral chemotherapy) such as alpha-interferon, prednisone (equivalent to >10 mg/day), or similar drugs
5. Treatment with any investigational medicinal product in another interventional clinical study currently or within 4 weeks before enrollment

1. Всякакви други нарушения на кръвосъсирването различни от
Хемофилия А
2. Анамнеза за FVIII инхибиторна активност (≥0.,6 BU) или
откриваеми FVIII инхибиторни антитела (≥0.,6 BU по
модификацията на Nijmegen на теста на Bethesda) на скрининга,
определени от централната лаборатория
3. Тежко чернодробно или бъбречно заболяване (нива на аланин
аминотрансфераза [AЛАТ] и аспартат трансаминаза [AСАТ] >5 пъти
над горната референтна граница, креатинин >120 μmol/L)
4. Пациенти, приемащи или с планиран прием на имуномодулиращи
лекарствени средства (различни от антиретровирусна химиотерапия),
като алфа-интерферон, преднизон (еквивалент на >10 mg/ден) или
подобни лекарства
5. Лечение с изпитван лекарствен продукт в друго интервенционално
клинично изпитване - текущо или до 4 седмици преди включване в
изпитването

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of this study is a 50% reduction of the total annualized bleeding rate (TABR) observed in the GENA-01 study, with a total of 58.1 BEs per patient per year.

Първичната крайна цел в това изпитване е намаляване с 50% на
общата годишна честота на кървене (TABR), наблюдавана в
изпитването GENA-01, при общо 58.1 периоди на кървене на пациент
годишно.

E.5.1.1

Timepoint(s) of evaluation of this end point

After the end of the study

След края на изпитването

E.5.2

Secondary end point(s)

The secondary endpoints of this study are the:
1. Spontaneous annualized bleeding rate (SABR)
2. Efficacy of Wilate in the treatment of breakthrough BEs based on the proportion of BEs successfully treated with Wilate
3. Descriptive efficacy of Wilate in surgical prophylaxis
4. Wilate consumption data (FVIII IU/kg per week per patient) for prophylaxis

Второстепенните крайни точки на това изпитване са:
1. Годишна честота на спонтанно кървене (SABR)
2. Ефикасност на Wilate при лечение на събития с пробивно кървене
според процента епизоди на кървене (ЕК), успешно лекувани с Wilate
3. Описателна ефикасност на Wilate в хирургичната профилактика
4. Данни за употреба на Wilate (FVIII IU/kg седмично на пациент) за
профилактика

E.5.2.1

Timepoint(s) of evaluation of this end point

After the end of the study

След края на изпитването

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

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

Yes

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

Yes

E.8.4

The trial involves multiple sites in the 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

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

Bulgaria

Hungary

Poland

Russian Federation

E.8.7

Trial has a data monitoring committee

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

Last patient last visit

Последен посещение на последен участник

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

Number of subjects for this age range:

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)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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

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)

standard of care

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

2016-11-29

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-03-29

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IMP with orphan designation in the indication
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