Clinical Trials Register

Summary
EudraCT Number:	2016-003438-26
Sponsor's Protocol Code Number:	161504
National Competent Authority:	Greece - EOF
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-10-11
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

Greece - EOF

A.2

EudraCT number

2016-003438-26

A.3

Full title of the trial

Post-Authorization Safety, Tolerability and Immunogenicity Evaluation of HyQvia in Pediatric Subjects with Primary Immunodeficiency Diseases

Μετεγκριτική αξιολόγηση της ασφάλειας, της ανεκτικότητας και της ανοσογονικότητας του HyQvia σε παιδιατρικούς ασθενείς με πρωτοπαθείς ανοσοανεπάρκειες.

A.3.1

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

Study to further assess the positive effect of the immunoglobulin product for subcutaneous use, HyQvia, in children (age <18 years) with Primary Immunodeficiency Diseases who have received prior immunoglobulin therapy before enrollment into the study.

Μελέτη για περαιτέρω αξιολόγηση της θετικής επίδρασης του προϊόντος ανοσοσφαιρίνης για υποδόρια χρήση «HyQvia» σε παιδιατρικούς ασθενείς (ηλικίας <18 ετών) με πρωτοπαθείς ανοσοανεπάρκειες που έχουν λάβει προηγούμενη θεραπεία με ανοσοσφαιρίνη πριν από την εγγραφή στη μελέτη.

A.4.1

Sponsor's protocol code number

161504

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	Baxalta US 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	Baxalta US 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	Baxalta US Inc.
B.5.2	Functional name of contact point	Fang Liu, Ph.D.
B.5.3	Address:
B.5.3.1	Street Address	650 E. Kendall St.
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	MA 02142
B.5.3.4	Country	United States
B.5.4	Telephone number	1-617-588-8193
B.5.5	Fax number	1-617-588-8210
B.5.6	E-mail	fang.liu@shire.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	Yes
D.2.1.1.1	Trade name	HyQvia 100 mg/ml solution for infusion for subcutaneous use
D.2.1.1.2	Name of the Marketing Authorisation holder	Baxalta Innovations GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	HyQvia
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Human normal immunoglobulin
D.3.9.3	Other descriptive name	HUMAN NORMAL IMMUNOGLOBULIN
D.3.9.4	EV Substance Code	SUB14196MIG
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	100
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	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	Yes
D.2.1.1.1	Trade name	KIOVIG 100 mg/ml solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Baxter AG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	KIOVIG
D.3.4	Pharmaceutical form	Solution for infusion
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 normal immunoglobulin
D.3.9.3	Other descriptive name	HUMAN NORMAL IMMUNOGLOBULIN (IV)
D.3.9.4	EV Substance Code	SUB12041MIG
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	100
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: 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	Yes
D.2.1.1.1	Trade name	Cuvitru 200 mg/ml solution for subcutaneous injection
D.2.1.1.2	Name of the Marketing Authorisation holder	Baxalta Innovations GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Austria
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	Cuvitru
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Human Normal Immunoglobulin
D.3.9.3	Other descriptive name	HUMAN NORMAL IMMUNOGLOBULIN
D.3.9.4	EV Substance Code	SUB14196MIG
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	200
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

Primary Immunodeficiency Disease (PIDD)

E.1.1.1

Medical condition in easily understood language

Conditions due to defects of the immune system

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10064859
E.1.2	Term	Primary immunodeficiency syndrome
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Safety of HyQvia treatment in pediatric subjects with PIDD who have received prior immunoglobulin therapy before enrollment into the study.

E.2.2

Secondary objectives of the trial

Further safety assessments (e.g. immunogenicity), tolerability, characteristic of product administration and efficacy (immunoglobulin G [IgG] trough levels).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject must have a documented diagnosis of a form of primary humoral immunodeficiency involving a defect in antibody formation and requiring
gammaglobulin replacement, as defined according to the IUIS (International Union of Immunological Societies) Scientific Committee 2015 1 prior to enrollment. The diagnosis must be confirmed by the sponsor Medical Director prior to first treatment with IP in the study.
2. Subject is at least two and below 18 years of age at the time of screening.
3. Subject has been receiving a consistent dose of IgG, administered in compliance with the respective product information for a period of at least three months prior to screening. The average minimum pre-study dose over that interval was equivalent to 300 mg/kg BW/four weeks and a maximum dose equivalent to 1000 mg/kg BW/4 weeks.
4. Subject has a serum trough level of IgG > 5 g/L at screening.
5. If female of childbearing potential, subject presents with a negative pregnancy test and agrees to employ adequate birth control measures for the duration of the study.
6. Subject/legally authorized representative is willing and able to comply with the requirements of the protocol.

E.4

Principal exclusion criteria

1. Subject has a known history of or is positive at screening for one or more of the following: hepatitis B surface antigen (HBsAg), polymerase chain reaction (PCR) for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1/2.
2. Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent):
a. Persistent alanine aminotransferase (ALT) and aspartate amino transferase (AST) >2.5 times the upper limit of normal (ULN) for the testing laboratory b. Persistent severe neutropenia (defined as an absolute neutrophil count [ANC] ≤ 500/mm3)
3. Subject has anemia that would preclude phlebotomy for laboratory studies, according to standard practice at the site.
4. Subject has an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IV immunoglobulin, SC immunoglobulin, and/or Immune Serum Globulin (ISG) infusions.
5. Subject has severe immunoglobulin A (IgA) deficiency (less than 7.0 mg/dL) with known anti-IgA antibodies and a history of hypersensitivity. .
6. Subject has a known allergy to hyaluronidase.
7. Subject has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening.
8. Subject has a bleeding disorder or a platelet count less than 20,000/μL, or who, in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of SC therapy.
9. Subject has severe dermatitis that would preclude adequate sites for safe product administration in the opinion of the investigator.
10. Subject has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to
participate in another clinical study involving an IP or investigational device during the course of this study.
11. Subject is a family member or employee of the investigator.
12. If female, subject is pregnant or lactating at the time of enrollment.

E.5 End points

E.5.1

Primary end point(s)

Number and rate per infusion (excluding infections) of all severe related AEs
Number and rate per infusion (excluding infections) of related SAEs

E.5.1.1

Timepoint(s) of evaluation of this end point

Yearly

E.5.2

Secondary end point(s)

Efficacy: Trough levels of IgG (for Study Epoch 1 and 2)

Safety/Tolerability:
Proportion of subjects who achieve a treatment interval of three or four weeks in Epoch 2
Proportion of subjects who maintain a treatment interval of three or four weeks in Epoch 2 for 12 months
Number and rate per infusion (excluding infections) of local AEs and ARs
Number and rate per infusion (excluding infections) of systemic AEs and ARs
Number and rate per infusion (excluding infections) of all AEs and all ARs
Number and rate per infusion (excluding infections) of all temporally associated AEs
Number and rate per infusion (excluding infections) of all causally related and/or temporally associated AEs
Number and rate per infusion (excluding infections) of all SAEs
Number/proportion of subjects who develop positive titer (≥160) of binding or neutralizing antibodies to rHuPH20

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy: Up to three years.

Safety: Up to one year.

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

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.8.3

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

E.8.6.2

Trial being conducted completely outside of the EEA

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 subject last 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)

F.1.3

Elderly (>=65 years)

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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.

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 treatment.

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

2017-11-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-10-27

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-01-15

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