Clinical Trials Register

Summary
EudraCT Number:	2005-003337-40
Sponsor's Protocol Code Number:	ASTIC
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2008-12-30
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2005-003337-40

A.3

Full title of the trial

Autologous Stem Cell Transplantation for Crohn’s Disease: Autologous Stem Cell Transplantation International Crohn’s Disease Trial A multicentre, prospective, randomised phase III study conducted by the European Crohn’s and Colitis Organisation (ECCO), sponsored by the Autoimmune Disease Working Party of the European Group for Blood and Marrow Transplantation (EBMT)

A.3.2

Name or abbreviated title of the trial where available

ASTIC

A.4.1

Sponsor's protocol code number

ASTIC

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	WOLFSON DIGESTIVE DISEASES CENTRE
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	ENDOXAN BAXTER
D.2.1.1.2	Name of the Marketing Authorisation holder	BAXTER SpA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Powder and solvent for solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Cyclophosphamide
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	THYMOGLOBULINE
D.2.1.1.2	Name of the Marketing Authorisation holder	GENZYME EUROPE B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Powder and solvent for solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Antithymocyte immunoglobulin (rabbit)
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	25
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
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

Crohn`s disease

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10013099
E.1.2	Term	Disease Crohns

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the potential clinical benefit of hematopoietic stem cell mobilisation followed by high dose immuno-ablation and autologous stem cell transplantation versus hematopoietic stem cell mobilisation only followed by best clinical practice in patients with Crohn’s disease

E.2.2

Secondary objectives of the trial

To evaluate the safety of Hematopoietic Stem Cell Transplantation (HSCT) in Crohn’s disease patients who have not responded to immunosuppressant medication To evaluate the impact of HSCT on health related, and generic, quality of life measures To identify factors predictive of success

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

ALTRI SOTTOSTUDI: mutazione NOD2 in pazienti con malattia di Crohn, ed altri eventuali studi genetici

E.3

Principal inclusion criteria

1)Age between 18 and 50 years a)Patients aged 50-65 can participate if specially approved by the Trial Steering Committee 2)Confirmed diagnosis of active Crohn’s Disease: a)Diagnosis of Crohn’s disease based on typical radiological appearances and / or typical histology b)Active disease at the time of registration to the trial, defined as i)Crohn’s disease activity index (CDAI) > 250 and > 2 of the following: ii)raised CRP, iii)endoscopic evidence of active disease confirmed on histology iv)clear evidence of active small bowel Crohn’s disease on small bowel barium study. 3)Unsatisfactory course despite 3 immunosuppressive agents (usually azathioprine, methotrexate and infliximab) in addition to corticosteroids. Patients should have relapsing disease (i.e. &#61619; 1 exacerbation/year) despite thiopurines, methotrexate and/or infliximab maintenance therapy or clear demonstration of intolerance / toxicity to these drugs. 4)Impaired function and quality of life, compared to population means, on at least one of the following: a)IBDQ (Appendix 6) b)European Questionnaire of Lifequality (EuroQOL–5D, Appendix 4) c)SF-36 Appendix 5) d)Impaired function on Karnofsky index (Appendix 7) 5)Current problems unsuitable for surgery and patient at risk for developing short bowel syndrome. 6)Informed consent (Sample Information Sheet and Consent Form given in Appendices 1 and 2 respectively) a)Prepared to enter controlled study. b)Prepared to undergo additional study procedures as per trial schedule c)Patient has undergone intensive counselling about risks d)Consent to future genotyping assessments is optional, but is not required for the patient to enter the trial

E.4

Principal exclusion criteria

1)Pregnancy or unwillingness to use adequate contraception during the study, if a woman of childbearing age 2)Concomitant severe disease a)renal: creatinine clearance < 40 ml/min (measured or estimated) b)cardiac: clinical evidence of refractory congestive heart failure; left ventricular ejection fraction < 45% by multigated radionuclide angiography (MUGA) or cardiac echo; chronic atrial fibrillation necessitating oral anticoagulation; uncontrolled ventricular arrhythmia; pericardial effusion with hemodynamic consequences as evaluated by an experienced echocardiographer c)psychiatric disorders including active drug or alcohol abuse d)concurrent neoplasms or myelodysplasia e)bone marrow insufficiency defined as leucocytopenia <3.0 x 10E9/l, thrombocytopenia <50 x 10E9/l, anemia < 8 g/dl, CD4+ T lymphopenia < 200 x 10E6/l f)uncontrolled hypertension, defined as resting systolic blood pressure &#8805; 140ml and/or resting diastolic pressure &#8805; 90ml mercury despite at least 2 anti-hypertensive agents. g)Uncontrolled acute or chronic infection with HIV, HTLV – 1 or 2, hepatitis viruses or any other infection the investigator or Steering Committee consider a contraindication to participation. h)Other chronic disease causing significant organ failure, including established cirrhosis with evidence of impaired synthetic function on biochemical testing and known respiratory disease causing resting arterial oxygen tension <8 kpa or carbon dioxide tension >6.7 kpa. Patients not known to have respiratory disease need not have blood gas measurements. i)Crohn’s Disease symptoms predominantly due to fibrotic stricturing and unlikely to respond to immune manipulation, in the opinion of any of the investigators or the steering committee 3)Diarrhoea due to short small or large bowel a)Patients believed to have <= 700 mm of small bowel or <= 300 mm of large bowel following ileo-rectal anastamosis and diarrhoea attributable to this, making assessment of Crohn’s disease activity index invalid should not enter the study 4)Infection or risk thereof a)Current abscess or significant active infection. b)Perianal sepsis is not an exclusion provided there is natural free drainage or a Seton suture(s) have been placed. c)History of tuberculosis or at current increased risk of tuberculosis d)Mantoux test result or other investigations that the investigator or Steering Committee regard as evidence of active tuberculosis. e)Abnormal chest x ray (CXR) consistent with active infection or neoplasm. 5)Significant malnutrition: Body Mass Index (BMI) &#8804; 18, serum albumin <=20 g/l 6)Previous poor compliance 7)Concurrent enrolment in any other protocol using an investigational drug or hematopoietic growth factor up to four weeks before study entry. 8)Lack of funding

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint will be the proportion of patients in sustained disease remission at one year. Sustained disease remission, based upon ECCO consensus is defined as: A minimum of a 3 month period of Crohn’s disease activity index (CDAI) <= 150 without steroids or immunosuppressive drugs and no mucosal erosion or ulceration at ileocolonoscopy and no definite evidence of small bowel Crohn’s Disease on barium studies.

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

Stesso trattamento in tempi diversi da leucaferesi

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

Information not present in EudraCT

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

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	No
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2008-12-30.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	12
F.4.2	For a multinational trial
F.4.2.1	In the EEA	48
F.4.2.2	In the whole clinical trial	48

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

2007-11-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-10-03

P. End of Trial
P.	End of Trial Status	Ongoing

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