Clinical Trials Register

Summary
EudraCT Number:	2011-005448-87
Sponsor's Protocol Code Number:	B1801315
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-03-21
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2011-005448-87

A.3

Full title of the trial

A RANDOMIZED, DOUBLE-BLIND PLACEBO-CONTROLLED STUDY OF THE MAINTENANCE OF EFFICACY OF ETANERCEPT PLUS DMARD(S) COMPARED WITH DMARD(S) ALONE IN SUBJECTS WITH RHEUMATOID ARTHRITIS AFTER ACHIEVING AN ADEQUATE RESPONSE WITH ETANERCEPT PLUS DMARD(S)

RANDOMIZÁLT, KETTŐS-VAK, PLACEBO-KONTROLLOS VIZSGÁLAT AZ ETANERCEPT PLUSZ DMARD(OK) ÉS AZ ÖNMAGUKBAN ALKALMAZOTT DMARD(OK) FENNTARTOTT HATÁSOSSÁGÁNAK ÉRTÉKELÉSÉRE RHEUMATOID ARTHRITISBEN SZENVEDŐ BETEGEKNÉL, AKIK MEGFELELŐEN REAGÁLTAK AZ ETANERCEPT PLUSZ DMARD KEZELÉSRE

A.3.1

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

A STUDY OF THE MAINTENANCE OF EFFICACY OF ETANERCEPT PLUS DMARD(S)
COMPARED WITH DMARD(S) ALONE IN SUBJECTS WITH RHEUMATOID ARTHRITIS AFTER ACHIEVING AN ADEQUATE RESPONSE WITH
ETANERCEPT PLUS DMARD(S)

VIZSGÁLAT AZ ETANERCEPT PLUSZ DMARD(OK) ÉS AZ ÖNMAGUKBAN ALKALMAZOTT DMARD(OK) FENNTARTOTT HATÁSOSSÁGÁNAK ÉRTÉKELÉSÉRE RHEUMATOID ARTHRITISBEN SZENVEDŐ BETEGEKNÉL, AKIK MEGFELELŐEN REAGÁLTAK AZ ETANERCEPT PLUSZ DMARD KEZELÉSRE

A.4.1

Sponsor's protocol code number

B1801315

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	Pfizer Inc, 235 East 42nd Street, New York, NY 10017
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	0013037391119
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® 50 mg Solution for Injection in Pre-filled Syringe
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer 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	185243-69-0
D.3.9.4	EV Substance Code	SUB01984MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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	Yes
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Rheumatoid Arthritis

Reumás ízületi gyulladás

E.1.1.1

Medical condition in easily understood language

Rheumatoid Arthritis

Reumás ízületi gyulladás

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10039073
E.1.2	Term	Rheumatoid arthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective 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 compare the maintenance of efficacy of the combination of ETN 50 mg once weekly plus MTX (± other DMARDs) therapy with that of MTX (± other DMARDs) at Week 52 in subjects with moderately to severely active RA who have achieved LDA (DAS28 ESR<3.2) after 24 weeks of therapy with open label ETN 50 mg once weekly plus MTX (± other DMARDs) in a treat to target paradigm.

A hetente egyszer 50 mg ETN plusz MTX (± egyéb DMARD) terápia és az MTX (± egyéb DMARD) terápia fenntartott hatásosságának összehasonlítása az 52. héten, közepesen súlyos vagy súlyos aktív RA-ban szenvedő olyan betegeknél, akik 24 hetes, nyílt elrendezésű, heti egyszer 50 mg ETN plusz MTX (± egyéb DMARD) terápia után elérték az LDA-t (DAS28-ESR<3,2), célzott kezelési séma alapján.

E.2.2

Secondary objectives of the trial

• To assess the clinical efficacy of the treatment regimens during Periods 1 and 2.

• To assess the maintenance of remission (DAS28<2.6) at Week 52 in those subjects who achieved remission after 24 weeks therapy with open label ETN 50 mg once weekly plus MTX (+ DMARDs).

• To assess the improvement in quality of life achieved and maintained by the treatment regimens over 52 weeks.

• To assess the improvement in physical function achieved and maintained by treatment regimens over 52 weeks.

• To assess the safety of the treatment regimens over 52 weeks.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team prior to subjects are included in the study. Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
• Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Period 1 Inclusion Criteria - Subjects must meet all of the following inclusion criteria to be eligible for enrollment in Period 1 of the study:
1. Subject is 18 to 70 years of age at the time of consent (eligible on the day of the 18th birthday and ends the day prior to their 70th birthday).
2. The subject has a minimum 1 year history/diagnosis of RA based on the 1987 American College of Rheumatology (ACR) Revised criteria for RA.
3. Subject must have active RA as defined below despite methotrexate (MTX) therapy of ≥10 mg/wk for at least 12 weeks. The MTX dose must be stable for at least 4 weeks immediately prior to screening.
4. Active RA is defined as: (a) disease activity score based on a 28 joint count (DAS28 ESR) >=3.2 and at least 1 of the following at screening and baseline: ≥6 tender joint count (TJC) and ≥6 swollen joint count (SJC) or ESR≥28 mm/hour and (b)C-reactive protein (CRP) ≥7.0 mg/L at screening.
5. Subject has a functional status of Class I, II, or III as defined by 1991 ACR revised criteria.
6. Women of childbearing potential must have had a negative serum pregnancy test at screening. Additionally, a urine test must be performed prior to administration of first dose of study medication, Week 52 and Early Discontinuation visit
7. Male and female subjects of childbearing potential must agree to use a medically accepted highly effective method of contraception throughout the study and for 3 months after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.
8. Female subjects who are not of childbearing potential (ie, meet at least one of the following criteria):
• Have undergone hysterectomy or bilateral oophorectomy;
• Have medically confirmed ovarian failure or;
• Are medically confirmed to be post menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause.
9. Subject must be able to self inject drug or have a designee who can do so and be able to store study medication as required or must be able to come to study site where the study medication may be stored.
10. Active and latent TB must be ruled out by screening for tuberculosis (TB) in accordance with local country guideline. A Quantiferron test must be performed unless not available. Subjects with recent exposure to active TB must be evaluated by a qualified physician to rule out Tuberculosis.
11. Subject is literate and able to complete questionnaires.
Period 2 Inclusion Criteria - The subject must meet all of the following criteria to be randomized into Period 2 of the study:
1. Subject has completed Period 1 of the study.
2. Subject has a DAS28 <3.2 at Week 24.
3. Subject must be willing to continue stable dose of all RA medication subject is using at Week 24 through Week 52 (except when dose adjustment is needed for an adverse event).

E.4

Principal exclusion criteria

Period 1 Exclusion Criteria:
1. Subjects, who are investigational site staff members directly involved
in the conduct of the trial and their family members, site staff members
otherwise supervised by the Investigator, or subjects who are Pfizer
employees directly involved in the conduct of the trial.
2. Subjects who used any of the following systemic treatments during
washout periods:
(a) Oral corticosteroid dose of prednisone >7.5 mg/day or a change in
dose w/in 28 days of baseline (BL)
(b)Treatment with >1 NSAID w/in 14 days at BL
(c) MTX dose > 25 mg/week, or change in dose w/in 28 days of BL
(d) Subjects allowed to continue the following: SZ, HCQ, & LEF. All other
non-biologic DMARDs & biologic DMARDs must have been discontinued
> 2 months prior to Week 0
(e) Any biologic B cell depleting agent w/in 2 years of Week 0.
3. known or suspected allergy, hypersensitivity, or contraindication to
ETN, its excipients, or other compounds related to this class of
medication.
4. received any live vaccine w/in 4 weeks prior to BL.
5. abnormal hematology or blood chemistry profile during screening (SC)
period. If SC lab tests are abnormal, repeat to confirm results. Results
from SC visit must be available at BL visit. BL lab results are not
required prior to first dose, but if results subsequently show that the
subject does not meet these exclusion levels & is confirmed upon retest,
subject must be withdrawn from study.
• White blood cell (WBC) count ≤3.5 x 10 to the power of 9/L;
• Hemoglobin level ≤85 g/L or ≤5.3 mmol/L;
• Hematocrit ≤27%;
• Platelet count ≤125 x 10 to the power of 9/L;
• Serum creatinine level ≥175 μmol/L (≥1.98 mg/dL);
• AST or ALT level ≥2 times the lab's upper limit of normal.
6. active & latent TB: Follow local guidelines for appropriate TB SC in the
setting of anti-TNF therapy, including a minimum of a chest radiograph &
objective TB testing. A PPD of >5 mm should be considered positive for
TB unless local guidelines for testing of immunocompromized (subjects
with RA) subjects is available & different. (a) Subjects with current or
recent (w/in 2 years of SC) active TB infection are excluded (b) Subjects
with history of active TB > 2 years ago & with documentation of
completing an adequate regimen of anti TB therapy may be considered
for enrollment after discussion with sponsor (c)Subjects with known
latent TB infection may be allowed only if local guidelines are followed
for prophylactic therapy & if TB chemoprophylaxis has been adequately
completed or initiated at least 4 weeks prior to Week 0 visit.
7. received TB chemoprophylaxis during SC &has had ALT and/or AST
>2x upper limit of normal [ULN] during this period. Subjects diagnosed
with TB & started chemoprophylaxis during SC period, additional blood
samples for ALT & AST must be drawn between 3-4 weeks after initiating
chemoprophylaxis. Results need to be reviewed prior to randomization.
8. serious infection w/in 1 month prior to Week 0 visit.
9. active infection at time of the SC visit and/or Week 0 visit, including
systemic fungal infections.
10. clinically relevant concurrent medical conditions.
11. anticipating surgical procedure during study period.
12. participating in other studies involving investigational drug(s)
(Phases 1-4) w/in 3 months of study.
13. pregnant females or those with a positive pregnancy test result at SC
or BL; breastfeeding females; males & females of childbearing potential
who are unwilling or unable to use a highly effective method of
contraception as outlined in this protocol for the duration of the study
and for 3 months after last study dose .
14. can satisfactorily complete the study
15. severe acute or chronic medical or psychiatric condition, substance abuse or lab abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results
16. illiterate.
Period 2 Exclusion Criteria
1.Subject has had a dose of prednisone >7.5 mg/day (or equivalent) or dose changed w/in 14 days before the randomization visit (Week 24).
2. Subject has had an oral MTX dose that has changed w/in 8 weeks before the Week 24 randomization visit (with the exception of a hold on the dose due to an AE). 3. Subject taking prohibited medications.

E.5 End points

E.5.1

Primary end point(s)

Proportion of subjects who remained in LDA (DAS28 ESR<3.2) at Week 52, among those who have achieved LDA at Week 24.

Azon betegek aránya, akiknél megmaradt az LDA (DAS28-ESR<3,2) az 52. héten azok közül, akik a 24. hétre elérték az LDA-t.

E.5.1.1

Timepoint(s) of evaluation of this end point

52 weeks

52 hét

E.5.2

Secondary end point(s)

• Proportion of subjects who remained in remission (DAS28 ESR<2.6) at Week 52, among those who have achieved remission at Week 24.
• Proportion of subjects in LDA or remission (by both DAS28 ESR and DAS28 CRP scores) at each visit during Period 1 & Period 2.
• Change from baseline in the DAS28 (-CRP and ESR) score at each visit during Period 1 and Period 2.
• Time-to-flare or loss of efficacy (loss of LDA plus ≥0.6 unit worsening in DAS28 ESR score) during Period 2.
• Proportion of subjects achieving European League Against Rheumatism (EULAR) good and or moderate responses (by both DAS28 ESR and DAS28 CRP scores) at each visit during Period 1 and Period 2.
• Proportion of subjects achieving LDA or remission at each visit during Period 1 and 2 based on CDAI and SDAI each visit during Period 1 and 2.
• Change of CDAI and SDAI at each visit during Period 1 and 2.
• Proportion of subjects achieving ACR 20, ACR 50, ACR 70 and ACR 90 (by 66/68 joint counts) during Period 1 and Period 2 at each visit.
• Change in the tender and swollen joint counts at each visit during Period 1 and Period 2 (using 28 joint count as well as 66/68 joint counts).
• Change in the Physician Global Assessment at each visit during Period 1 and Period 2.
• Change in the Subject Global Assessment, including morning stiffness (measured in minutes) at each visit during Period 1 and Period 2.
• Change in the Subject General Health visual analog scale (VAS), and Pain VAS at each visit during Period 1 and Period 2.
• Change in CRP and ESR at each visit during Period 1 & Period 2.

E.5.2.1

Timepoint(s) of evaluation of this end point

Throughout the study and at 52 weeks

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

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)

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

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Note: period 1 is open label

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

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

Argentina

Brazil

China

Colombia

Czech Republic

Egypt

Hungary

India

Malaysia

Mexico

Philippines

Poland

Romania

Russian Federation

Saudi Arabia

Slovakia

South Africa

Taiwan

Thailand

Turkey

Ukraine

United Arab Emirates

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

LSLV

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:

304

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

124

F.4.2.2

In the whole clinical trial

320

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)

None

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

2012-05-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-05-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-03-27

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials