Clinical Trials Register

Summary
EudraCT Number:	2007-007129-38
Sponsor's Protocol Code Number:	CE1226_3001
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-04-01
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

Denmark - DHMA

A.2

EudraCT number

2007-007129-38

A.3

Full title of the trial

An open-label, non-controlled, multicenter, multinational Study to evaluate the Efficacy and Safety of Zemaira® administration in Chronic Augmentation and Maintenance Therapy in Subjects with Emphysema due to Alpha1-Proteinase Inhibitor Deficiency who completed Clinical Study CE1226_4001

A.3.1

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

Clinical research study to assess the safety and effectiveness of alpha1-proteinase inhibitor (A1-PI) administered by intravenous application to patients with alpha1-proteinase deficiency and emphysema who have completed the 2-year treatment and observation period in the Phase III/IV Zemaira® CE1226_4001.

A.4.1

Sponsor's protocol code number

CE1226_3001

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	CSL Behring GmbH
B.1.3.4	Country	Germany
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	CSL Behring GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CSL Behring GmbH
B.5.2	Functional name of contact point	Global Project Lead
B.5.3	Address:
B.5.3.1	Street Address	Emil-von-Behring-Str. 76
B.5.3.2	Town/ city	Marburg
B.5.3.3	Post code	35041
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49 6421 39-2929
B.5.5	Fax number	+49 6421 39-3172
B.5.6	E-mail	anja.braeunlich@cslbehring.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	Alpha1-Proteinase Inhibitor / Zemaira®
D.3.2	Product code	CE1226
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	There is no recommended INN.
D.3.9.2	Current sponsor code	CE1226
D.3.9.3	Other descriptive name	Alpha1-Proteinase Inhibitor (Human)
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000
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 augmentation and maintenance therapy in individuals with alpha1-proteinase inhibitor (A1-PI) deficiency and clinical evidence of emphysema.

E.1.1.1

Medical condition in easily understood language

Chronic hereditary, genetic disorder in which there is not enough of this protein to prevent lung damage and is associated with progressive, severe emphysema.

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10001811
E.1.2	Term	Alpha-1 proteinase inhibitor deficiency
E.1.2	System Organ Class	100000004850

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 investigate the long-term verification of a disease-modifying benefit of Zemaira® on the progression of emphysema, assessed by volume-adjusted lung density, and measured by yearly computed tomography (CT).

E.2.2

Secondary objectives of the trial

The secondary objectives are to assess the effect of treatment with A1-PI on:
1. change in symptoms score as assessed by Quality of Life (QoL) using the St. George’s Respiratory Questionnaire (SGRQ);
2. the assessment of pulmonary function (ie, forced expiratory volume in 1 second [FEV1] and [FEV1/forced vital capacity{FVC}]);
3. reduction in risk of pulmonary exacerbations assessed by the number and annual rate of exacerbations over the study duration;
4. antigenic and functional serum A1-PI levels in relation to disease progression, body mass index (BMI), safety, and mortality.
5. the safety profile of subjects will be assessed throughout the study.
The safety of Zemaira® will be assessed by the occurrence of adverse events (AEs).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subjects who have completed the 2-year treatment and observation period in the Phase 3/4 Zemaira® CE1226_4001 study and are willing to sign informed consent.

2. Males, and non-pregnant, non-lactating females, whose screening pregnancy test is negative and who are using contraceptive methods deemed reliable by the investigator.

E.4

Principal exclusion criteria

1. Individuals residing in the US.

2. Current evidence of alcohol abuse, or abuse of drugs, such as barbiturates, benzodiazepines, amphetamines, cocaine, opioids, and cannabinoids.

3. History of allergy, anaphylactic reaction, or severe systemic response to human plasma derived products, or known mannitol hypersensitivity, or history of prior adverse reaction (AR) to mannitol.

4. Current tobacco smoker (i.e. smoking must be discontinued for at least 6 months prior to study participation).

5. Conditions or behaviors that interfere with attending scheduled study visits, in the opinion of the investigator.

6. History of non-compliance.

7. Administration of any other experimental new drug or participation in an investigation of a marketed product.

8. Inability to perform necessary study procedures.

E.5 End points

E.5.1

Primary end point(s)

Primary Efficacy Variable: Annual Rate of Change in adjusted P15 from CT Scans

The exploratory efficacy variable of primary interest is the annual rate of change, measured by a slope of time and treatment interaction from a mixed effects model, in volume-adjusted lung density. This is assessed by the 15th percentile (P15) of the lung density distribution. The variable of interest is called adjusted P15 measured in g/L. Scans are obtained at total lung capacity (TLC) and functional residual capacity (FRC) inspiration state, and lung volume is assessed for the right, the left, and for both lungs. During the extension study, the CT scans are taken at Month 12 and Month 24 (ie, Month 36 [Visit 5] and Month 48 [Visit 9] when consideration is given to the start of study CE1226_4001). The primary interest of the study will be comparing the annual rate of change in adjusted P15 from CT scans between subjects who had an early start with Zemaira® treatment and subjects who had a late start with treatment over 4 years.

E.5.1.1

Timepoint(s) of evaluation of this end point

See E.5.1

E.5.2

Secondary end point(s)

Key Secondary Efficacy Variable: Absolute and % Change in Adjusted P15 from Baseline to Month 48

The absolute and % change from baseline to the Month 48 will be derived using the values of adjusted P15 of the last assessment of CT scans from study CE1226_3001 and the first assessment of CT scans from study CE1226_4001.

E.5.2.1

Timepoint(s) of evaluation of this end point

See E.5.2

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

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

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)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

Australia

Canada

Czech Republic

Denmark

Estonia

Finland

Germany

Ireland

Sweden

Poland

Romania

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

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:

125

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

140

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)

Supply of Zemaira® on named-patient basis from the U.S. or, alternatively, use of competitor products

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

2009-05-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-06-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-09-09

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