Clinical Trials Register

Summary
EudraCT Number:	2014-005496-87
Sponsor's Protocol Code Number:	161403
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:	2016-08-03
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

Greece - EOF

A.2

EudraCT number

2014-005496-87

A.3

Full title of the trial

A Phase III Study to Evaluate the Efficacy, Safety, and Tolerability of Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase (HYQVIA/HyQvia) and Immune Globulin Infusion (Human), 10% (GAMMAGARD LIQUID/KIOVIG) for the Treatment of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

A.3.1

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

Study to asses if the immunoglobulin product for subcutaneous use in combination with Hyaluronidase has a positive effect on your disease, and if it safe to use. The study will also assess if the intravenous immunoglobulin product has a positive effect and is safe to use.

A.3.2

Name or abbreviated title of the trial where available

Phase III Efficacy, Safety, and Tolerability Study of HyQvia and KIOVIG in CIDP

A.4.1

Sponsor's protocol code number

161403

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02549170

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 Innovations GmbH
B.1.3.4	Country	Austria
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 Innovations GmbH
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Takeda Pharmaceutical Company Limited
B.5.2	Functional name of contact point	Jennifer McCall
B.5.3	Address:
B.5.3.1	Street Address	650 East Kendall Square
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(828)244-7874
B.5.6	E-mail	jennifer.mccall@takeda.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)	Yes
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	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)	Yes
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic inflammatory demyelinating polyradiculoneuropathy

E.1.1.1

Medical condition in easily understood language

Chronic Inflammatory Demyelinating Polyneuropathy is a rare disorder of the peripheral nerves (nerves outside the central nervous system) caused by damage to the covering of the nerves, called myelin.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10057645
E.1.2	Term	Chronic inflammatory demyelinating polyradiculoneuropathy
E.1.2	System Organ Class	10029205 - Nervous system 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

Epoch 1:SC Treatment Period

1.To evaluate the efficacy of HyQvia as a maintenance therapy for CIDP to prevent relapse of neuromuscular disability and impairment.

Epoch 2: IV Treatment Period

1.To evaluate the efficacy of KIOVIG for the treatment of CIDP to improve neuromuscular disability and impairment.

E.2.2

Secondary objectives of the trial

Epoch 1:SC Treatment Period

1. To assess the time to CIDP relapse during maintenance therapy with HyQvia, compared to placebo.
2. To assess the effect of HyQvia on activities of daily living (ADL).
3. To assess the safety and tolerability of HyQvia.
4. To monitor for the presence of binding and neutralizing anti-rHuPH20 antibodies following HyQvia administration.

Epoch 2: IV Treatment Period

1. To assess the safety and tolerability of KIOVIG.
2. To assess the effect of GAMMAGARD LIQUID/KIOVIG on activities of daily living.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Males or females of age ≥18 years old at the time of screening.
2. Subject has a documented diagnosis of definite or probable CIDP (focal atypical CIDP and pure sensory atypical CIDP will be excluded).
3. Subject has responded to IgG treatment in the past, (partial or complete resolution of neurological symptoms and deficits), and must currently be on stable doses of IGIV treatment within the dose range equivalent to a cumulative monthly dose of 0.4 to 2.4 g/kg BW (inclusive) administered intravenously for at least 3 months prior to screening. The dosing interval of IGIV treatment must be between 2 to 6 weeks (inclusive).
4. INCAT disability score between 0 to 7 (inclusive). Subjects with INCAT scores of 0, 1 (whether from upper or lower extremities), or 2 (if at least 1 point is from an upper extremity) at screening and/or baseline will be required to have a history of significant disability as defined by an INCAT disability score of 2 (must be exclusively from the lower extremities) or greater within 24 months prior to screening.
5. If female of childbearing potential, the subject must have a negative pregnancy test at screening and agree to employ a highly effective contraceptive measure throughout the course of the study and for at least 30 days after the last administration of investigational product.
6. Subject is willing and able to sign an Informed Consent Form (ICF).
7. Subject is willing and able to comply with the requirements of the protocol.

E.4

Principal exclusion criteria

1.Subjects with focal atypical CIDP or pure sensory atypical CIDP.
2. Any neuropathy of other causes, including:
a. Hereditary demyelinating neuropathies, such as hereditary sensory
and motor neuropathy (Charcot-Marie-Tooth [CMT] disease), and
hereditary sensory and autonomic neuropathies.
b. Neuropathies secondary to infections, disorders, or systemic diseases
such as Borrelia burgdorferi infection (Lyme disease), diphtheria,
systemic lupus erythematosus, POEMS (polyneuropathy, organomegaly,
endocrinopathy, M-protein, and skin changes) syndrome, osteosclerotic
myeloma, diabetic and non-diabetic lumbosacral radiculoplexus
neuropathy, lymphoma, and amyloidosis
c. Multifocal acquired demyelinating sensory and motor neuropathy
(MADSAM)
d. Multifocal motor neuropathy
e. Drug-, biologic-, chemotherapy-, or toxin-induced peripheral
neuropathy
3. Immunoglobulin M (IgM) paraproteinemia, including IgM monoclonal
gammopathy with high titer antibodies to myelin-associated
glycoprotein.
4. Presence of prominent sphincter disturbance.
5. Any central demyelinating disorders such as multiple sclerosis.
6. Any chronic or debilitating disease, or central nervous disorder that
causes neurological symptoms or may interfere with assessment of CIDP
or outcome measures, including (but not limited to) arthritis, stroke, and
Parkinson's disease and diabetic peripheral neuropathy.
7. The subject has received or is currently receiving treatment with
immunomodulatory/immunosuppressive agents within 6 months prior to
screening.
8. The subject has received or is currently receiving treatment with any
corticosteroids dose within 8 weeks prior to screening, regardless of
indication.
9. The subject has undergone plasma exchange within 3 months prior to
screening.
10. The subject has any disorder or condition that in the investigator's
judgment may impede the subject's participation in the study, pose
increased risk to the subject, or confound the results of the study.
11. The subject is nursing or intends to begin nursing during the course
of the study.
12. Subjects with acquired or inherited thrombophilic disorders. These
will include the specific types of acquired or inherited thrombophilic
disorders that could put subjects at risk of developing thrombotic
events.

E.5 End points

E.5.1

Primary end point(s)

Epoch 1: SC Treatment Period
Relapse rate
Epoch 2: IV Treatment Period
Responder rate

E.5.1.1

Timepoint(s) of evaluation of this end point

Epoch 1: SC Treatment Period
up to 6 months
Epoch 2: IV Treatment Period
up to 6 months

E.5.2

Secondary end point(s)

Epoch 1: SC Treatment Period
Efficacy
1.Proportion of subjects who experience a worsening of functional disability defined as an increase of ≥1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability scores OR who experience CIDP worsening (defined as a ≥8 kPa decrease in the hand grip strength in the more affected hand) OR ≥4 points decrease in R-ODS relative to the pre-SC treatment baseline score at 2 consecutive time points (at the time of withdrawal from the SC treatment period)
2.Time to relapse
3.Change from pre-SC treatment baseline in R-ODS

Safety
Number (%) of subjects with AE's
Number (%) of AEs associated with infusions
Number (%) of infusion rate reduction/interruption/discontinuation due to AE,
Incidence of anti-rHuPH20 antibodies
Rates of systemic and local AEs

Epoch 2: IV Treatment Period

Safety
Number (%) of subjects with AE's
Number (%) of AEs associated with infusions
Number (%) of infusion rate reduction/interruption/discontinuation due to AE
Rates of systemic and local AEs

Efficacy
1. Proportion of subjects with clinically meaningful improvement in functional ability defined as a decrease of ≥1 point in the adjusted INCAT disability score OR who experience CIDP improvement (defined as ≥8 kPa increase in the hand grip strength in the more affected hand OR ≥4 points increase in R-ODS) at the completion of the IV treatment period [6 months] or at the last study visit of the IV treatment period, relative to the pre-IV treatment baseline score

E.5.2.1

Timepoint(s) of evaluation of this end point

up to 6 months

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)

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Epoch 1: Double blind. Epoch 2: open label

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

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

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

Mexico

Peru

Serbia

Turkey

Belgium

Canada

Croatia

Czechia

Denmark

Germany

Greece

Israel

Italy

Netherlands

Norway

Russian Federation

Slovakia

Spain

Sweden

Switzerland

United Kingdom

United States

France

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

study completion is 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

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)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

110

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

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

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

130

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

2016-09-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-09-28

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-02-23

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