Clinical Trials Register

Summary
EudraCT Number:	2013-000525-31
Sponsor's Protocol Code Number:	20120262
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:	2013-09-30
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

2013-000525-31

A.3

Full title of the trial

A Randomized, Double-blind, Phase 3 Study of ABP 501 Efficacy and Safety Compared to Adalimumab in Subjects with Moderate to Severe Rheumatoid Arthritis

RANDOMIZÁLT, KETTŐS VAK, 3. FÁZISÚ VIZSGÁLAT AZ ABP 501 HATÁSOSSÁGÁNAK ÉS BIZTONSÁGOSSÁGÁNAK ADALIMUMABBAL SZEMBENI MEGHATÁROZÁSÁRA MÉRSÉKELT-SÚLYOS REUMATOID ARTRITISZBEN SZENVEDŐKNÉL

A.3.1

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

The trial is designed to determine the safety and efficacy of ABP 501 compared with Adalimumab in subjects with moderate to severe rheumatoid arthritis

A.4.1

Sponsor's protocol code number

20120262

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	Amgen Inc
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	Amgen 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	Amgen (Europe) GmbH
B.5.2	Functional name of contact point	IHQ Medical Info-Clinical Trials
B.5.3	Address:
B.5.3.1	Street Address	Dammstrasse 23, PO Box 1557
B.5.3.2	Town/ city	Zug
B.5.3.3	Post code	CH-6300
B.5.3.4	Country	Switzerland
B.5.6	E-mail	Medinfointernational@amgen.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	No
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.3.1	Product name	ABP 501
D.3.2	Product code	ABP 501
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
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.3.9.2	Current sponsor code	ABP 501
D.3.9.3	Other descriptive name	Biosimilar product to adalimumab
D.3.9.4	EV Substance Code	SUB74962
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	Yes
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.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	Humira
D.2.1.1.2	Name of the Marketing Authorisation holder	AbbVie 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.3.1	Product name	Adalimumab
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
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	ADALIMUMAB
D.3.9.1	CAS number	331731-18-1
D.3.9.3	Other descriptive name	Humira
D.3.9.4	EV Substance Code	SUB20016
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	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Moderate to Severe Rheumatoid Arthritis

E.1.1.1

Medical condition in easily understood language

Moderate to Severe Rheumatoid Arthritis

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

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

The primary objective for this study is to assess the efficacy of ABP 501 compared with adalimumab.

E.2.2

Secondary objectives of the trial

The secondary objectives are to assess the safety and immunogenicity of ABP 501 compared with adalimumab.

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

All enrolled subjects are eligible to participate in the optional pharmacogenetic testing substudy
Objectives: These optional pharmacogenetic analyses focus on inherited genetic variations to evaluate their possible correlation to the disease and/or responsiveness to the therapies used for RA. The goals of the optional substudy include the use of genetic markers to help in the investigation of RA and/or to identify subjects who may have positive or negative response to treatment.

E.3

Principal inclusion criteria

1.Subjects must sign an IRB/IEC-approved ICF before any study specific procedures
2.Men or women ≥ 18 and ≤ 80 years old
3.Subjects must be diagnosed with RA as determined by meeting 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA
4.Duration of RA of at least 3 months
5.Active RA defined as ≥ 6 swollen joints and ≥ 6 tender joints (based on 66/68 joint count excluding distal interphalangeal joints) at screening and baseline and at least one of the following at screening:
•ESR ≥ 28 mm/hr
•serum CRP > 1.0 mg/dL
6.Positive rheumatoid factor or anti-cyclic citrullinated peptide (CCP) at screening
7.Subjects must be taking MTX for ≥ 12 consecutive weeks and on a stable dose of 7.5 to 25 mg/week for > 8 weeks prior to receiving the study drug and be willing to remain on stable dose throughout the study
8.For subjects on nonsteroidal anti-inflammatory drugs (NSAIDs) or low potency analgesics such as tramadol, soma compounds, fioricet, fiorinal, dose should be stable for ≥ 2 weeks prior to screening
9.For subjects on oral corticosteroids, (≤ 10 mg prednisone or equivalent), stable doses for ≥ 4 weeks prior to screening
10.Subject has no known history of active tuberculosis
11.Subject has a negative test for tuberculosis during screening defined as either:
•negative purified protein derivative (PPD; < 5 mm of induration at 48 to 72 hours after test is placed) OR
•negative Quantiferon test
12.Subjects with a positive PPD and a history of Bacillus Calmette-Guérin vaccination are allowed with a negative Quantiferon test
13.Subjects with a positive PPD test (without a history of Bacillus Calmette-Guérin vaccination) or subjects with a positive or indeterminate Quantiferon test are allowed if they have all of the following:
•no symptoms per tuberculosis worksheet provided by the sponsor, Amgen
•documented history of adequate prophylaxis initiation prior to receiving study drug in accordance with local recommendations
•no known exposure to a case of active tuberculosis after most recent prophylaxis
•no evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of IP

E.4

Principal exclusion criteria

Rheumatoid Arthritis related
1.Class IV RA according to ACR revised response criteria (Section 17.2)
2.Felty’s syndrome (RA, splenomegaly, and granulocytopenia)
3.History of prosthetic or native joint infection
Other medical conditions
4.Planned surgical intervention during the duration of the study
5.Active infection or history of infections as follows:
•any active infection for which systemic anti-infectives were used within 28 days prior to first dose of IP
•a serious infection, defined as requiring hospitalization or intravenous (IV) anti infectives within 8 weeks prior to the first dose of investigational product
•recurrent or chronic infections or other active infection that, in the opinion of the Investigator, might cause this study to be detrimental to the subject
6.Known history of human immunodeficiency virus
7.Hepatitis B surface antigen (HbsAg) or Hepatitis C virus (HCV) antibody positivity at screening
8.Uncontrolled, clinically significant systemic disease such as diabetes mellitus, cardiovascular disease including moderate to severe heart failure (New York Heart Association [NYHA] class III/IV), renal disease, liver disease or hypertension
9.Malignancy within 5 years EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma
10.History of neurologic symptoms suggestive of central nervous system demyelinating disease
11.Major chronic inflammatory disease or connective tissue disease other than RA, with the exception of secondary Sjögren’s syndrome
12.Concurrent medical condition that, in the opinion of the Investigator, could cause this study to be detrimental to the subject
Laboratory abnormalities
13.Laboratory abnormalities at screening, including any of the following:
•Hemoglobin < 9 g/dL
•Platelet count < 100,000/mm3
•White blood cell count < 3,000 cells/mm3
•Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≥ 2.0 x the upper limit of normal
•Creatinine clearance < 50 mL/min (Cockroft-Gault formula)
•Any other laboratory abnormality, which, in the opinion of the Investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is risk ratio (RR) of ACR20 (20% improvement in ACR core set measurements)

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary efficacy endpoint is risk ratio (RR) of ACR20 (20% improvement in ACR core set measurements) at week 24. To achieve ACR20 response, at least 20% improvement compared to baseline is required for both swollen and tender joint counts), as well as for 3 out of the following 5 additional parameters:
•Subject's Global Health Assessment (on a 0 to 10 horizontal scale)
•Investigator's Global Health Assessment (on a 0 to 10 horizontal scale)
•Subject's assessment of pain (on a 100-mm visual analogue scale (VAS);
•Health Assessment Questionnaire – Disability Index
•CRP

E.5.2

Secondary end point(s)

Secondary efficacy endpoints include change from baseline of DAS28-CRP, RR of ACR20 responses, and RR of ACR50 (50% improvement in ACR core set measurements) and ACR70 (70% improvement in ACR core set measurements)

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary efficacy endpoints include change from baseline of DAS28-CRP at each time point (weeks 2, 4, 8, 12, 18, and 24), RR of ACR20 responses at weeks 2 and 8, and RR of ACR50 and ACR70 responses at week 24.

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

ADA - anti-drug antibody testing is being performed

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

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.8.2.4

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

Bulgaria

Canada

Czech Republic

Germany

Hungary

Mexico

Poland

Romania

Russian Federation

Spain

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

last visit, last subject

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:

450

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

238

F.4.2.2

In the whole clinical trial

500

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

2013-09-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-09-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-11-19

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