Clinical Trials Register

Summary
EudraCT Number:	2018-003592-34
Sponsor's Protocol Code Number:	AUH-2018-100
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-03-14
Trial 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

Denmark - DHMA

A.2

EudraCT number

2018-003592-34

A.3

Full title of the trial

Subcutaneous immunoglobulin in de-novo CIDP
(Randomized, parallel study of subcutaneous versus intravenous immunoglobulin in treatment-naïve patients with chronic inflammatory demyelinating polyneuropathy)

Subkutan immunglobulin ved de-novo CIDP
(Randomiseret, parallel studie af subkutan versus intravenøs immunglobulin behandling ved nydiagnosticerede patienter med kronisk inflammatorisk demyeliniserende polyneuropati)

A.3.1

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

Subcutaneous versus intravenous administration of immunoglobulin in newly diagnosed patients with chronic inflammatory neuropathy

Subkutan versus intravenøs behandling med immunglobulin hos nydiagnosticerede patienter med kronisk inflammatorisk nervebetændelse

A.3.2

Name or abbreviated title of the trial where available

SIDEC

A.4.1

Sponsor's protocol code number

AUH-2018-100

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	Aarhus University Hospital
B.1.3.4	Country	Denmark
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	CSL Behring AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Aarhus University Hospital
B.5.2	Functional name of contact point	Lars Kjøbsted Markvardsen
B.5.3	Address:
B.5.3.1	Street Address	Palle Juul-Jensens Boulevard 99
B.5.3.2	Town/ city	Aarhus N
B.5.3.3	Post code	8200
B.5.3.4	Country	Denmark
B.5.4	Telephone number	004578450000
B.5.5	Fax number	004578463300
B.5.6	E-mail	larsmark@rm.dk

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	Hizentra
D.2.1.1.2	Name of the Marketing Authorisation holder	CSL Behring
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	Hizentra
D.3.4	Pharmaceutical form	Concentrate for solution for injection/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 Immunoglobulin G
D.3.9.3	Other descriptive name	HUMAN IMMUNOGLOBULIN G
D.3.9.4	EV Substance Code	SUB127300
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Privigen
D.2.1.1.2	Name of the Marketing Authorisation holder	CSL Behring
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	Privigen
D.3.4	Pharmaceutical form	Concentrate for solution for injection/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 Immunoglobulin G
D.3.9.3	Other descriptive name	HUMAN IMMUNOGLOBULIN G
D.3.9.4	EV Substance Code	SUB127300
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.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

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Kronisk inflammaotrisk demyeliniserende polyneuropati (CIDP)

E.1.1.1

Medical condition in easily understood language

Chronic inflammatory neuropathy

Kronisk inflammatorisk nervebetændelse

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	10064135
E.1.2	Term	Polyneuropathy chronic
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

To evaluate the effect of SCIG versus IVIG in de-novo CIDP patients during a treatment period of 26 weeks (phase I)

E.2.2

Secondary objectives of the trial

To evaluate a standardized reduction of dosage regimen to identify the lowest effective dosage of immunoglobulin (phase II).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients diagnosed with typical or pure motor CIDP fulfilling the European Federation of Neurological Societies / Peripheral Nerve Society (EFNS/PNS) clinical and elctrophysiological criteria for definite or propable CIDP
Age > 18 and <80 years at inclusion
Overall disability sum score (ODSS) > 1

E.4

Principal exclusion criteria

Previous treatment with immmunoglobulin
Pregnancy
Malignancies
Other causes of neuropathy (Diabetes Mellitus)
Severe medical diseases
Other immunomodulating treatment in the last 6 weeks prior to inclusion
Hepatitis B and C or HIV
Lactation

E.5 End points

E.5.1

Primary end point(s)

Change in Overall Disability Sum score (ODSS) measured by questionnaire from baseline until end of phase I (26 weeks)

Change in Overall Disability Sum score (ODSS) measured by questionnaire from start of phase II and until the lovest effective dosage of immunoglobulin has been reached (up til 60 weeks)

E.5.1.1

Timepoint(s) of evaluation of this end point

Phase I:
All patients will be evaluated at baseline (week 0) and re-evaluated at week 2, 4, 14, 20 and 26

Phase II:
All patients will be evaluated every 12th week according to lovering of the dosage of immunoglobulin

E.5.2

Secondary end point(s)

Change in parameters describing muscle strength and sensory:
o Grip strength, MRC-score, isokinetic dynamometry, INCAT Sensory Sum Score (ISSS)

Change in parameters describing functional ability:
o 10-meter-walk test (10-MWT), 6-spot-step test (6-SST), 9-hole-peg test (9-HPT)

Change in parameters describing disability, quality of life, pain and treatment satisfaction:
QoL (EQ-5D-5L), Fatigue Severity Scale (FSS), Neuropathic Pain Symptom Inventory (NPSI), Rasch built overall disability scale (RODS) and Treatment Satisfaction Questionnaire for Medication (TSQM)

Serum samples: Plasma IgG (IgG1, IgG2, IgG3, IgG4)

Hematology: hemoglobin, reticulocyte count, haptoglobin, bilirubin, plasma haemoglobin, leukocyte count, thrombocyte count.

Fluctuations in describing parameter in each arm at pre-defined time points according to IVIG infusions (pre versus post IVIG):
o Week 0, 4 and 20 versus week 2, 14 and 26

E.5.2.1

Timepoint(s) of evaluation of this end point

Phase I:
All patients will be evaluated at baseline (week 0) and re-evaluated at week 2, 4, 14, 20 and 26
At week 10 a telephone interview will be done to evaluate treatment response.

Phase II:
All patients will be evaluated every 12th week according to tappering of the dosage of immunoglobulin

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

Yes

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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

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

Yes

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)

Yes

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

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

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

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

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:

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