Clinical Trials Register

Summary
EudraCT Number:	2009-013220-24
Sponsor's Protocol Code Number:	3.0
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-03-19
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

Czechia - SUKL

A.2

EudraCT number

2009-013220-24

A.3

Full title of the trial

Plasma Exchange and Glucocorticoid in the Treatment of Anti-neutrophil Cytoplasm Antibody Associated Vasculitis: an International Randomised Controlled Trial.

Výměnná plazmaferéza a dávkování kortikosteroidů v léčbě vaskulitid asociovaných s protilátkami proti cytoplazmě neutrofilních leukocytů (ANCA-asociovaných vaskulitid): mezinárodní, randomizovaná, kontrolovaná studie.

A.3.1

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

Plasma Exchange and Glucocorticoid in the Treatment of Anti-neutrophil Cytoplasm Antibody Associated Vasculitis: an International Randomised Controlled Trial.

Výměnná plazmaferéza a dávkování glukokortikoidů v léčbě ANCA-asociovaných vaskulitid: multicentrická, randomizovaná, kontrolovaná studie.

A.3.2

Name or abbreviated title of the trial where available

PEXIVAS

A.4.1

Sponsor's protocol code number

3.0

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN07757494

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00987389

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	Cambridge University Hospitals NHS Trust
B.1.3.4	Country	United Kingdom
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	Medical Research Council
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	National Institutes of Health Research
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	Food and Drug Administration Office for Orphan Product Development
B.4.2	Country	United States
B.4.1	Name of organisation providing support	National Institute of Health
B.4.2	Country	United States
B.4.1	Name of organisation providing support	Canadian Institutes of Health Research
B.4.2	Country	Canada
B.4.1	Name of organisation providing support	National Health and Medical Research Council
B.4.2	Country	Australia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Vasculitis Research Office, Box 246,Addenbrooke´s Hospital
B.5.2	Functional name of contact point	Biljana Brezina
B.5.3	Address:
B.5.3.1	Street Address	Hills Road
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	CB2 0QQ
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441223256731
B.5.5	Fax number	+441223586767
B.5.6	E-mail	biljana.brezina@addenbrookes.nhs.uk

D. IMP Identification
D.IMP: 1
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	Prednison 20 Léčiva
D.2.1.1.2	Name of the Marketing Authorisation holder	Zentiva, k.s.
D.2.1.2	Country which granted the Marketing Authorisation	Czech Republic
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.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Prednisolone
D.3.9.1	CAS number	8056-11-9
D.3.9.4	EV Substance Code	AS2
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	20 mg
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	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	Prednison 5 Léčiva
D.2.1.1.2	Name of the Marketing Authorisation holder	Zentiva, k.s.
D.2.1.2	Country which granted the Marketing Authorisation	Czech Republic
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.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Prednisolone
D.3.9.1	CAS number	8056-11-9
D.3.9.4	EV Substance Code	AS1
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	5 mg
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	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

ANCA associated vasculitis

ANCA-asociovaná vaskulitida

E.1.1.1

Medical condition in easily understood language

ANCA associated vasculitis

vaskulitida vázaná na ANCA protilátky

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	18.1
E.1.2	Level	PT
E.1.2	Classification code	10050894
E.1.2	Term	Anti-neutrophil cytoplasmic antibody positive vasculitis
E.1.2	System Organ Class	10021428 - Immune 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

There are 2 principal questions for this research:
1) Does the addition of 7 plasma exchange procedures to usual therapy early in the treatment of patients with severe ANCA associated vasculitis significantly reduce their risk of death or kidney failure?
2) Does a reduced-dose regimen of steroids compared to a standard-dose regimen in the first 6 months of treatment of patients with ANCA associated vasculitis significantly reduce their risk of death or kidney failure?

E.2.2

Secondary objectives of the trial

1) Does the addition of plasma exchange or a reduced dose regimen of steroids lead to differences in disease control in patients with ANCA associated vasculitis?
2) Does the addition of plasma exchange or a reduced dose regimen of steroids lead to a difference in adverse events in patients with ANCA associated vasculitis?
3) Does the addition of plasma exchange or a reduced dose regimen of steroids lead to a difference in health related quality of life in patients with ANCA associated vasculitis?

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) New or previous diagnosis of ANCA associated vasculitis
2) Positive test, at any point in the subject´s disease course, by ELISA, for proteinase 3-ANCA or myeloperoxidase - ANCA
3) Has a severe manifestation of vasculitis as defined by either a) renal vasculitis resulting in an estimated glomerular filtration rate below 50 ml/min; or b) lung haemorrhage
4) Provision of informed consent by patient or a surrogate decision maker

E.4

Principal exclusion criteria

1) Presence of concomitant anti-glomerular basement membrane disease or another vasculitic disease
2) Requirement for dialysis for >21 days in the period immediately preceeding enrollment
3) Age <15 (In the Czech Republic age < 18)
4) Pregnancy
5) Inability or unwillingness to comply with birth control/abstinence
6) Treatment for vasculitis with cyclophosphamide and/or glucocorticoids for >14 days prior to randomisation or rituximab >28 days prior to randomisation
7) A comorbidity on condition that, in the opinion of the investigator, precludes the use of cyclophosphamide/rituximab, glucocorticoids, or plasma exchange or absolutely mandates the use of plasma exchange.
8) Plasma Exchange in 3 months prior to randomization.

E.5 End points

E.5.1

Primary end point(s)

Composite of i) All-cause mortality or ii) End-stage kidney failure

E.5.1.1

Timepoint(s) of evaluation of this end point

at all study visits until at least 12 months after randomization

E.5.2

Secondary end point(s)

The secondary objectives will be assessed using the following outcome measures: sustained remission, all cause of mortality, end stage renal disease (ESRD), serious adverse events, serious infections, Medical Outcome Survey Short Form (SF-36), Euro QoL EQ5D Index score.

E.5.2.1

Timepoint(s) of evaluation of this end point

at all study visits until at least 12 months after randomization;
SF-36 and EQ5D will be assessed at baseline and at weeks 12, 26, 52 and then every 26 weeks until study termination.

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

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

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

1) no plasma exchange 2) standard dose glucocorticoids (GCs)

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

Australia

Canada

Czech Republic

Denmark

Germany

Italy

Mexico

New Zealand

Norway

Spain

Sweden

Switzerland

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

The trial is planned to stop 12 months after the last patient is enrolled (common closing date).

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1