Clinical Trials Register

Summary
EudraCT Number:	2012-004606-10
Sponsor's Protocol Code Number:	8VWF07
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2016-06-29
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2012-004606-10

A.3

Full title of the trial

Multicentre, Non-controlled, Prospective, Post-Marketing Safety Study Following Long-Term Prophylactic Optivate® Treatment in Subjects with Severe Haemophilia A.

A.3.1

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

Post-Marketing Study to monitor the safety of long term treatment with Optivate in patients with Haemophilia A.

A.3.2

Name or abbreviated title of the trial where available

Post Marketing study following long term prophylactic Optivate usage

A.4.1

Sponsor's protocol code number

8VWF07

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01811875

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	Bio Products Laboratory Limited
B.1.3.4	Country	United Kingdom
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	Bio Product Laboratory Limited
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bio Products Laboratory Limited
B.5.2	Functional name of contact point	Lisa Wilson
B.5.3	Address:
B.5.3.1	Street Address	Dagger Lane
B.5.3.2	Town/ city	Elstee
B.5.3.3	Post code	WD6 3BX
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	4402089572240
B.5.5	Fax number	4402089572611
B.5.6	E-mail	lisa.wilson@bpl.co.uk

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	Optivate
D.2.1.1.2	Name of the Marketing Authorisation holder	Bio Products Laboratory Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Optivate
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	Human coagulation factor VIII
D.3.9.2	Current sponsor code	8VWF07
D.3.9.3	Other descriptive name	Optivate
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	up to
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.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 Haemophilia A

E.1.1.1

Medical condition in easily understood language

Severe bleeding disorder

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The main aim is to assess factor VIII inhibitor development levels for a minimum of 100 treatment days per patient. Each patient will have 4 factor VIII recovery assessments over a period of approximately 12 months. At each recovery assessment the patient will have a factor VIII inhibitor test before being infused with Optivate®. This is to help assess the continued safety of Optivate® by monitoring the potential development of inhibitors.

E.2.2

Secondary objectives of the trial

The study will also assess the efficacy by measuring factor VIII concentration in the blood and tolerability by assessing adverse events recorded during the study.
The recovery assessment will measure the increase in factor VIII concentration in the patient during the first hour following Optivate® infusion. In addition, efficacy will be assessed based on patients diary data e.g. adverse events, number of bleeds, severity, duration etc. This is to help assess the efficacy and tolerability of Optivate® treatment.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Written informed consent or, in the case of children and adolescents (less than 18 years of age) have given written assent (where possible) and whose parent/guardian has given written informed consent.

- Severe haemophilia A (< 1% FVIII:C). Subjects suffering from severe haemophilia A
(< 2%) may be enrolled, but only after approval by BPL. Subjects with a FVII
< 2% may not constitute more than 50% of the total patient population. A separate
statistical evaluation will be conducted for the < 1% and < 2% populations. Basal
FVIII level taken from subject’s lowest level recorded, or the level measured at screening, whichever is lower.

- Previously Treated Patients (PTPs) with > 150 exposure days on prior FVIII therapy (of
which at least the last 50 EDs or 2 years treatment can be confirmed by way of subject
records).

- Immunocompetent subjects with CD4 (cluster differentiation 4) count > 200 /μL.

- Human Immunodeficiency Virus (HIV) negative subjects or a viral load < 200 particles
/μL.

E.4

Principal exclusion criteria

- History of inhibitor development to FVIII or a positive result on the Nijmegen-Bethesda at screening (quantitative result of > 0.6 Bethesda Units [BU]) prior to the administration of Optivate®.

- Known or suspected hypersensitivity to the Investigational Medicinal Product (IMP) or its excipients.

- Clinically significant i.e. symptomatic liver disease and/or (historical, within the last 12 months, serum Alanine Aminotransferase [ALT] levels greater than three times the
upper limit of the normal range), symptomatic renal disease and/or (historical, within the last 12 months, serum creatinine > 200mol/L), or coagulopathy other than haemophilia A.

- History of unreliability or non-cooperation (including not being able to complete the study diary).

- Participating in, or have taken part in another trial within the last 30 days.

E.5 End points

E.5.1

Primary end point(s)

The primary outcome is to measure the immunogenicity of Optivate® by monitoring plasma inhibitor levels for at least 100 treatment days for each patient. Inhibitor assessments at each visit will be measured using two methods:

1. Pre-infusion blood samples for FVIII inhibitor screens
2. Quantitative assay called Nijmegen-Bethesda Assay

E.5.1.1

Timepoint(s) of evaluation of this end point

Pre-bolus dose at screening, baseline, V2, V3 and V4.

E.5.2

Secondary end point(s)

FVIII Concentration to measure optivate recoveries.

E.5.2.1

Timepoint(s) of evaluation of this end point

At the screening visit, baseline visit and V2, V3 and V4 blood samples will be taken at the following intervals:

Pre-bolus dose
15 minutes post dose
30 minutes post dose
60 minutes post dose

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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.8.3

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

Colombia

Germany

Poland

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

End of trial will be defined as when 10 evaluable patients have completed 100 exposure days of Optivate® treatment and the safety follow-up visit.

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

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

Yes

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)

Optivate® will be provided free of charge during the course of the study. As the product is commercially available the patients doctor will have the option to continue the patients treatment with Optivate®, if in the best interests of the patient.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-10-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-07-12

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2017-06-29

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