Clinical Trials Register

Summary
EudraCT Number:	2015-000958-38
Sponsor's Protocol Code Number:	LFB-FVIIa-007-14
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:	2016-02-29
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

Bulgarian Drug Agency

A.2

EudraCT number

2015-000958-38

A.3

Full title of the trial

A Phase III Study on the Safety, Pharmacokinetics, and Efficacy of Coagulation Factor VIIa (Recombinant) in Congenital Hemophilia A or B Pediatric Patients from birth to <12 years old with Inhibitors to Factor VIII or IX: PerSept 2

A.3.1

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

A clinical study with a Factor VIIa (Recombinant) to evaluate its efficacy, its safety and its behaviour in human blood in pediatric patients from birth to less than 12 years of age with Hemophilia A or B with inhibitors to factor VIII or IX

A.3.2

Name or abbreviated title of the trial where available

PerSept 2

A.4.1

Sponsor's protocol code number

LFB-FVIIa-007-14

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02448680

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/103/2016

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	LFB USA, 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	LFB USA, 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	LFB USA, Inc.
B.5.2	Functional name of contact point	Clinical Project Manager
B.5.3	Address:
B.5.3.1	Street Address	175 Crossing Boulevard
B.5.3.2	Town/ city	Framingham
B.5.3.3	Post code	MA 01702
B.5.3.4	Country	United States
B.5.4	Telephone number	15083705258
B.5.5	Fax number	15083703797
B.5.6	E-mail	margaret.carini@lfb-usa.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Coagulation Factor VIIa (Recombinant)
D.3.2	Product code	LR769
D.3.4	Pharmaceutical form	Powder 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	NA
D.3.9.1	CAS number	8000026-55-3
D.3.9.2	Current sponsor code	LR769
D.3.9.3	Other descriptive name	FACTOR VIIA
D.3.9.4	EV Substance Code	SUB13812MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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	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

Congenital Hemophilia A or B patients with inhibitors to Factor VIII or Factor IX

E.1.1.1

Medical condition in easily understood language

Hereditary hemophilia which is caused by a shortage of Factor VIII (Hemophilia A) or Factor IX (Hemophilia B), which is complicated by inhibitors to factor treatment, making this ineffective

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.1
E.1.2	Level	PT
E.1.2	Classification code	10056492
E.1.2	Term	Haemophilia A with anti factor VIII
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.1
E.1.2	Level	PT
E.1.2	Classification code	10056494
E.1.2	Term	Haemophilia B with anti factor IX
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

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 assess the efficacy of 2 separate dose regimens (75 µg/kg and 225 µg/kg) of LR769 for the treatment of bleeding episodes in hemophilia A or B pediatric patients from birth to <12 years old with inhibitors to factor VIII or IX
To assess the safety of LR769. This includes the immunogenic potential of the drug product

E.2.2

Secondary objectives of the trial

To assess the PK of LR769 in hemophilia A or B pediatric patients from birth to <12 years old,with inhibitors to factor VIII or IX, without a current bleeding episode

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. be male with a diagnosis of congenital hemophilia A or B of any severity
2. have one of the following:
a. a positive inhibitor test BU ≥5, OR
b. a BU<5 but expected to have a high anamnestic response to FVIII or FIX, as demonstrated from the patient’s medical history, precluding the use of factor VIII or IX products to treat bleeding episodes, OR
c. a BU<5 but expected to be refractory to increased dosing of FVIII or FIX, as demonstrated from the patient’s medical history, precluding the use of factor VIII or IX products to treat bleeding episodes
3. be aged from birth to <12 years of age
4. have experienced at least 3 bleeding episodes of any severity in the past 6 months; if < 6 months old, have experienced at least 3 bleeding episodes since birth
5. parents or legal guardians must be capable of understanding and willing to comply with the conditions of the protocol
6. parents or legal guardians must have read, understood and provided written informed consent

E.4

Principal exclusion criteria

1. have any coagulation disorder other than hemophilia A or B
2. be immunosuppressed (i.e., the patient should not be receiving systemic immunosuppressive medication, CD4 counts at screening should be >200/µl)
3. have a known allergy or hypersensitivity to rabbits
4. have platelet count <100,000/μL
5. have had a major surgical procedure (e.g. orthopedic, abdominal) within 1 month prior to first administration of the study drug in this study
6. have received an investigational drug within 30 days of the first study drug administration, or is expected to receive such drug during participation in this study
7. have a clinically relevant hepatic (AST and/or ALT >3 times ULN) and/or renal impairment (creatinine >2 times ULN)
8. have an active malignancy (those with non-melanoma skin cancer are allowed)
9. have any life-threatening disease or other disease or condition which, in the investigator’s judgment, could imply a potential hazard to the patient, or interfere with the trial participation or trial outcome (e.g., a history of non-responsiveness to bypassing products or thromboembolic disease)
10. known or suspected hypersensitivity to the active substance or to any of its excipients

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is defined as successful treatment of a bleeding episode at 12 hours after first administration of the study drug. The following are clarification definitions to satisfy regulatory requirements in multiple regions (i.e., the FDA and the EMA). Definition of the primary efficacy endpoint for the FDA: the successful treatment of a bleeding episode at 12 hours after first administration of the study drug. For primary efficacy endpoint for the FDA only treatment of mild/moderate bleeding episodes are taken into account. Efficacy in severe bleeding episodes will be described separately.
For primary efficacy endpoint for the FDA, successful treatment of a bleeding episode is defined as a combination of the following:
• Good or Excellent response noted by patient/parent guardian, depending on patient’s age and maturity
• Study drug treatment: No further treatment with study drug beyond timepoint for this bleeding episode where a Good or Excellent response was noted
• No other haemostatic treatment needed for this bleeding episode
• No administration of blood products indicating continuation of bleeding beyond timepoint where a Good or Excellent response for this bleeding episode was noted
• No increase of pain beyond timepoint where a Good or Excellent response for this bleeding episode was noted that cannot be explained other than as continuation of bleeding

Primary efficacy endpoint for EMA is the proportion of bleeding episodes (mild/moderate and severe combined) with a “good” or “excellent” patient (for mild/moderate bleeding episodes) and physician (for severe bleeding episodes) reported assessment of efficacy at 12 hours after the first administration of study drug.

E.5.1.1

Timepoint(s) of evaluation of this end point

The time point for the primary evaluation of efficacy will be at 12 hours after first administration of study drug

E.5.2

Secondary end point(s)

• Proportion of mild/moderate bleeding episodes successfully treated, according to the same criteria as the primary endpoint of efficacy, at all other timepoints
• Proportion of bleeding episodes (mild/moderate and severe, separately and combined) with a “good” or “excellent” patient (and/or physician when available) reported assessment of the efficacy at all timepoints
• Time to assessment of a “good” or “excellent” response of the bleeding episodes (mild/moderate and severe, separately and combined) by the patient/parent (and/or physician when available)
• The number of administrations and total amount of drug administered per bleeding episode

E.5.2.1

Timepoint(s) of evaluation of this end point

At the end of study

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

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

Yes

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

Yes

E.8.1.1

Randomised

Yes

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

Yes

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

Yes

E.8.2.3.1

Comparator description

Same IMP at different dose regimen

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

Colombia

Czech Republic

France

Hungary

Italy

Mexico

South Africa

Turkey

Ukraine

United Kingdom

United States

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

LVLS

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)

Yes

F.1.1.3.1

Number of subjects for this age range:

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

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)

None

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

2016-03-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-03-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-06-30

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