Clinical Trials Register

Summary
EudraCT Number:	2008-004439-39
Sponsor's Protocol Code Number:	0881X1-4535-WW
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-12-18
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

Germany - BfArM

A.2

EudraCT number

2008-004439-39

A.3

Full title of the trial

Randomized Open-label Study Comparing 2 Different Strategies For Management of Subjects With Plaque Psoriasis Who Have Responded to Etanercept Treatment

A.3.1

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

A clinical study comparing 2 different strategies for management of subjects with Plaque Psoriasis who have responded to Etanercept treatment

A.3.2

Name or abbreviated title of the trial where available

ReSPONSE

A.4.1

Sponsor's protocol code number

0881X1-4535-WW

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	Wyeth Research Division of Wyeth Pharmaceuticals Inc. A Pfizer Company,Philadelphia,PA-19101,USA
B.1.3.4	Country	United States
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	Pfizer Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pfizer Inc.
B.5.2	Functional name of contact point	Clinical Trials.gov Call Center
B.5.3	Address:
B.5.3.1	Street Address	235 East 42nd Street
B.5.3.2	Town/ city	New York
B.5.3.3	Post code	NY 10017
B.5.3.4	Country	United States
B.5.4	Telephone number	0018007181021
B.5.5	Fax number	001303739 1119
B.5.6	E-mail	ClinicalTrials.gov_Inquiries@pfizer.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	Yes
D.2.1.1.1	Trade name	Enbrel 25mg solution for injection in pre-filled syringe
D.2.1.1.2	Name of the Marketing Authorisation holder	Wyeth Europa Ltd
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Solution for injection
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	ETANERCEPT
D.3.9.1	CAS number	185243690
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	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	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	Enbrel 50mg solution for injection in pre-filled syringe
D.2.1.1.2	Name of the Marketing Authorisation holder	Wyeth Europa Ltd
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Solution for injection
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	ETANERCEPT
D.3.9.1	CAS number	185243690
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)	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

Plaque psoriasis

E.1.1.1

Medical condition in easily understood language

Plaque psoriasis

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.0
E.1.2	Level	PT
E.1.2	Classification code	10037153
E.1.2	Term	Psoriasis
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue disorders

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 describe the effect on subjects in whom psoriasis has responded to initial treatment with etanercept (ETN) of two different strategies for managing a good response or complete response (PGA= 1 or 0) over a 52 week period..

E.2.2

Secondary objectives of the trial

• To compare the efficacy of the 2 different strategies by reference to quality of life measure over the duration of the study
• To explore the time course of severity following treatment modification
• To explore the degree of subject satisfaction with the two different options for management following successful initial treatment

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Eighteen (18) years of age or older at time of consent.
2. Previously treated with ETN for chronic plaque PSO for at least 12 weeks prior to the screening visit, and received a total weekly dose of 50 mg per week for at least the 6 weeks preceding the day of the screening visit.
3. Having shown clinical response with a PGA ≤ 1 at the screening visit.
4. With a PGA ≤ 1 at the baseline visit.
5. Where the last injection of ETN was performed not more than 7 days before the baseline visit.
6. Able to store the injectable investigational product under refrigerated conditions.
7. Able to self-inject investigational product or have a designee who can do so.
8. Able to complete health outcome assessments and any study diaries.
9. Demonstrates an adequate screening for tuberculosis (TB) prior to initiation of therapy with ETN, in accordance with local country guidelines Since ETN has been prescribed prior to the enrollment in the study, tests results and/or radiographic report must be available at site.
10. Is a man or woman who is surgically sterile or is at least 1 year postmenopausal. A woman not surgically sterile or at least 1 year postmenopausal must demonstrate a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline, and must agree and commit to use medically acceptable forms of contraception.
All female subjects who are also taking known teratogens, eg methotrexate, acitretin, must agree and commit to use contraceptive precautions as recommended by the respective SPCs, data sheets or equivalent legal documents. In addition, all male subjects taking concomitant methotrexate who are biologically capable of having children must agree and commit to the use of a reliable method of birth control for the duration of the study and for 6 months after the last dose of methotrexate

E.4

Principal exclusion criteria

1. Evidence of skin conditions (eg, eczema) other than PSO that would interfere with evaluations of the effect of study medication on PSO.
2. Evidence of active or previously known medical history of inflammatory arthritis (eg, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis).
3. Any biologics other than ETN within the 20 weeks prior to the screening visit.
4. Cyclosporin, within 28 days of the baseline visit.
5. Receipt of any live (attenuated) vaccine within 4 weeks before baseline.
6. Sunbathing or UV treatment for therapeutic reasons (ultraviolet light A [UVA], psoralen and ultraviolet light A therapy [PUVA], or ultraviolet light B [UVB] therapy, including narrow band UVB and excimer laser) within 28 days of the baseline visit.
7. Oral, intravenous, intramuscular, intra-articular, and subcutaneous (SC) corticosteroids within 28 days of the baseline visit. Exception: inhaled corticosteroids for the treatment of pulmonary conditions and topical ophthalmic solutions containing corticosteroids with or without antibiotics for episodes of acute ocular inflammation are permitted.
8. Abnormal hematology or blood chemistry profile at screening:
- hemoglobin ≤85 g/L;
- hematocrit ≤27%;
- platelet count ≤125 x 10 to the power of 9/L;
- white blood cell count ≤3.5 x 10 to the power of 9/L;
- serum creatinine (Creat) ≥175 μmol/L;
- aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥2 times the laboratory’s upper limit of normal (ULN).
Exclusionary screening laboratory tests that are considered, in the opinion of the investigator, to be due to an error or a transient condition, may be repeated once during the screening period for confirmation.
9. Clinically relevant concurrent medical events including:
- Serious infection (infection associated with hospitalization and/or intravenous antibiotics) within 1 month before investigational product administration or active infection at screening, including known human immunodeficiency virus (HIV) infection.
- Current or recent (within 2 years of screening) active TB infection (Note: local country guidelines should be followed for appropriate TB screening and prophylaxis in the setting of anti-TNF therapy, including a minimum of a chest radiograph and/or objective TB testing, such as purified protein derivative [PPD] or Quantiferon depending on what is acceptable per local guidelines).
- Untreated latent TB. Subjects with latent TB infection may be allowed only if local guidelines are followed for prophylactic therapy and if treatment is initiated before therapy, followed by proof that no adverse drug reaction has occurred with the anti-TB medications.
- Uncontrolled hypertension (defined as screening systolic blood pressure >160 mm Hg or screening diastolic blood pressure >100 mm Hg).
Exclusionary blood pressure measurements that are considered, in the opinion of the investigator, to be due to an error or a transient condition, may be repeated once during the screening period for confirmation.
- Myocardial infarction within 12 months of the screening visit.
- Unstable angina pectoris within 6 months of the screening visit.
- Class III or IV congestive heart failure as defined by the New York Heart Association.
- Severe pulmonary disease requiring hospitalization or supplemental oxygen within 12 months of screening.
- Known history or presence of hepatitis B or hepatitis C infection, including known presence of alcoholic hepatitis
- History of human immunodeficiency virus (HIV) infection, immunodeficiency syndromes
- Diagnosis of multiple sclerosis or other central or peripheral nervous system demyelinating diseases
- Presence or history of confirmed blood dyscrasias
- Uncontrolled diabetes mellitus
- Open cutaneous ulcers
- Presence or history of cancer (or carcinoma in situ) other than resected cutaneous basal cell or squamous cell carcinoma within the past 5 years before the screening visit
10. Known contraindication or hypersensitivity to ETN or its excipients.
11. History of or current psychiatric illness that would interfere with the subject’s ability to comply with protocol requirements or give informed consent.
12. History of alcohol or drug use that, in the investigator’s clinical judgment, would interfere with the subject’s ability to comply with protocol requirements.
13. History of anti-cardiolipin antibodies associated with a thrombotic event or recurrent fetal loss.
14. Received any investigational drug within 3 months of screening visit
15. Pregnant or breast-feeding women

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the average 52 week PGA (measured as the time-normalized area under curve)

E.5.1.1

Timepoint(s) of evaluation of this end point

Describe the effect on subjects in whom Psoriasis has responded with Good response or Complete response (PGA = 1or 0) over a 52-week time period

E.5.2

Secondary end point(s)

Key secondary endpoints:
1. Time-normalized area under the DLQI vs time curve.
2. Patient satisfaction with PSO treatment at baseline, before retreatment with ETN 50 mg weekly, and at the end of retreatment.
3. Mean PGA at week 52.

Other secondary exploratory endpoints:
1. Proportion of time that subjects achieve a PGA of 0 or 1.
2. Time to a first retreatment with ETN 50 mg, starting from randomization.
3. Proportion of subjects who achieve PGA of 0 or 1.
4. Time to achieve a PGA of 0 or 1, starting from the time of dose escalation.
5. Change from baseline in the PGA at the each visit during the 52 weeks.
6. Change from baseline in the PASI at the each visit during the 52 weeks.
7. Patient acceptability of current PSO symptoms at baseline before restarting ETN 50 mg weekly until decreasing the dose again as per the randomization.
8. EQ-5D.
9. SGA
10. Change in scores on WPAI: PSO.
11. Change in data captured on the Subject Pharmacoeconomic Questionnaire

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Compare the efficacy of the 2 different strategies by reference to quality of life (QoL) measure over the duration of the study.
2. To explore the time course of severity following treatment modification.
3. To explore the degree of subject satisfaction with the 2 different options for management following successful initial treatment.

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

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Comparison btwn stop arm which is contrl grp & maintenance arm (low dose group).

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

France

Germany

Greece

Hungary

Italy

Spain

Turkey

United Arab Emirates

United Kingdom

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

Last phone call to the last subject as per protocol.

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