Clinical Trials Register

Summary
EudraCT Number:	2005-001549-41
Sponsor's Protocol Code Number:	0881-A3-402-WW
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-10-09
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2005-001549-41

A.3

Full title of the trial

A Randomised, Double-Blind Study Evaluating the Safety and Efficacy of Etanercept and Sulphasalazine in Subjects with Ankylosing Spondylitis

A.3.2

Name or abbreviated title of the trial where available

ASCEND

A.4.1

Sponsor's protocol code number

0881-A3-402-WW

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	WYETH LEDERLE
B.1.3.4	Country	Italy
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
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	Enbrel
D.2.1.1.2	Name of the Marketing Authorisation holder	WYETH EUROPA LTD
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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 injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Etanercept
D.3.9.1	CAS number	185243-69-0
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	50
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)	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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile
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	Salazopyrin En-Tabs
D.2.1.1.2	Name of the Marketing Authorisation holder	Pharmacia Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Sulfasalazine
D.3.9.1	CAS number	599-79-1
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	500
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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile

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	Powder and solvent for solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Subjects with Ankylosing Spondilitis (AS)

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	10002556
E.1.2	Term	Ankylosing spondylitis

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 compare the efficacy of etanercept 50 mg once weekly with SSZ 3 g daily in the treatment of AS subjects over 16 weeks. The study hypothesis is that etanercept 50 mg once weekly will demonstrate superior clinical efficacy, as determined by the proportion of responders achieving a 20% improvement on the Assessment of AS (ASAS) response criteria (ASAS 20) at 16 weeks, compared with SSZ 3 g daily in the treatment of AS subjects.

E.2.2

Secondary objectives of the trial

1.To compare the effect of etanercept 50 mg once weekly with SSZ 3 g daily on the quality of life over 16 weeks
2.To evaluate the safety of etanercept 50 mg once weekly over 16 weeks

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Diagnosis of AS, as defined by Modified New York Criteria for Ankylosing Spondylitis.
2.Active AS, defined on a scale of 0 to 100 by:
·Average duration and intensity of morning stiffness visual analogue scale (VAS) of nlt 30;
·At least 2 of the following:
-Patient global assessment VAS nlt 30;
-Average nocturnal and total pain VAS nlt 30;
-Bath Ankylosing Spondylitis Functional Index (BASFI) VASnlt 30.
3.Presence of peripheral arthritis, defined as nlt 1 tender/painful and swollen peripheral joint or nlt 1 tender/painful hip or shoulder joint.
4.Treatment failure to at least one NSAID of at least three months duration at the maximal recommended or tolerated anti-inflammatory dose, unless NSAIDs are contraindicated.
5.18 years of age or older at time of consent.
6.Negative serum pregnancy test taken at screening in all women except those who were surgically sterile or at least 1 year postmenopausal.Sexually active women of childbearing potential participating in the study must use a medically acceptable form of contraception.
7.Agreement by male subjects who are not surgically sterile and female subjects who are not surgically sterile or postmenopausal to use reliable methods of birth control for the duration of the study.
8.Ability to self-inject drug or have a designee who can do so.
9.Capable of understanding and willing to provide signed and dated written voluntary informed consent before any protocol specific procedures are performed.
10.Ability to store injectable test article at 2o C to 8o C.

E.4

Principal exclusion criteria

1.Complete ankylosis (fusion) of spine.
2.Previous treatment with etanercept, antibody to tumour necrosis factor a (TNFa), or other TNFa inhibitors or other biologic agents.
3.Treatment with SSZ within 6 months of screening.
4.History of treatment with SSZ associated with significant toxicity or significant lack of response.
5.Contraindication to SSZ including:
·Hypersensitivity to SSZ, its metabolites, sulfonamides, or salicylates
·History or presence of intestinal or urinary obstruction
·History or presence of porphyria
·Current treatment with digoxin
6.Failure to respond to treatment to more than one DMARD.
7.Use of DMARDs other than methotrexate or hydroxychloroquine within 4 weeks of baseline. Subjects on methotrexate or hydroxychloroquine must have been on a stable dose for at least 4 weeks prior to randomisation.
8.Receipt of more than one DMARD concurrently at screening.
9.Previous use of intravenous bisphosphonate.
10.Receipt of more than one NSAID concurrently at baseline.
11.Dose of NSAID changed within 2 weeks of baseline.
12.Dose of prednisone >10 mg/day (or equivalent) or changed within 2 weeks of baseline.
13.Receipt of intra-articular, intravenous, intramuscular, or subcutaneous corticosteroid within 4 weeks of screening.
14.Abnormality in haematology or chemistry profiles: haemoglobin £ 85 g/L; haematocrit nmt 27%; platelet count nmt 125 x 109 /L; white blood cell count nmt 3.5 x 109 /L; serum creatinine nlt 175 mmol/L; aspartate aminotransferase (AST [SGOT]) and alanine aminotransferase (ALT [SGPT]) nlt 2 times the laboratory’s upper limit of normal.
15.Significant concurrent medical events including:
·Uncontrolled hypertension (defined as screening systolic blood pressure > 160 mm Hg or screening diastolic blood pressure > 100 mm Hg)
·Myocardial infarction within 12 months of the screening visit
·Unstable angina pectoris
·Class III or IV congestive heart failure as defined by the New York Heart Association classification (16) or uncompensated congestive heart failure
·Severe pulmonary disease requiring hospitalisation or supplemental oxygen
·Diagnosis of multiple sclerosis or other central demyelinating diseases
·Presence or history of confirmed blood dyscrasias
·Uncontrolled diabetes mellitus
·Rheumatoid arthritis, systemic lupus erythematosus, scleroderma, or polymyositis
·Cancer or history of cancer (other than resected cutaneous basal cell or squamous cell carcinoma)
·Serious infection (infection associated with hospitalisation and/or intravenous antibiotics) within 1 month of test article administration or active infection at screening
·Open cutaneous ulcers
·Known human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) positive
·Tuberculosis (TB) infection
·Any condition that, in the investigator’s judgment, might cause this study to be detrimental to the subject
16. Receipt of any live (attenuated) vaccine within 4 weeks prior to baseline
17. Known contraindication or hypersensitivity to etanercept or its excipients.
18. Pregnant or breast-feeding women.
19. Reasonable expectation that the subject will not be able to satisfactorily complete the study
20. History of or current psychiatric illness that would interfere with the subject’s ability to comply with protocol requirements or give informed consent.
21. History of alcohol or drug abuse that would interfere with the subject’s ability to comply with protocol requirements.
22. Receipt of any investigational drug within 3 months of screening visit.
23. Employment by the investigator or reporting directly or indirectly to the investigator

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint will be the proportion of subjects who achieve ASAS 20 at Week 16 relative to baseline.

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

Yes

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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.8.3

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.8.6 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

Information not present in EudraCT

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

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

La fine dello studio e' l’ultima visita dell’ultimo soggetto.

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)	Yes
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 2008-10-09.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Information not present in EudraCT
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	48
F.4.2	For a multinational trial
F.4.2.1	In the EEA	450
F.4.2.2	In the whole clinical trial	525

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

2006-02-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2006-02-06

P. End of Trial
P.	End of Trial Status	Completed

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