Clinical Trials Register

Summary
EudraCT Number:	2014-000109-11
Sponsor's Protocol Code Number:	FKB327-002
National Competent Authority:	Bulgarian Drug Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-10-10
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

Bulgarian Drug Agency

A.2

EudraCT number

2014-000109-11

A.3

Full title of the trial

A Randomised, Blinded, Active-Controlled Study to Compare FKB327 Efficacy and Safety with the Comparator Humira® in Rheumatoid Arthritis Patients Inadequately Controlled on Methotrexate.

A.3.1

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

Study to assess the efficacy and safety of FKB327 compared with Humira®, when each is administered in combination with Methotrexate in patients with Rheumatoid Arthritis.

A.3.2

Name or abbreviated title of the trial where available

ARABESC

A.4.1

Sponsor's protocol code number

FKB327-002

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	Fujifilm Kyowa Kirin Biologics Co., Ltd.
B.1.3.4	Country	Japan
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	Fujifilm Kyowa Kirin Biologics Co., Ltd.
B.4.2	Country	Japan
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fujifilm Kyowa Kirin Biologics Co., Ltd., EU Branch
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	Enterprise House Unit 12A, Galabank Business Park,
B.5.3.2	Town/ city	Galashiels
B.5.3.3	Post code	TD1 1PR
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441896 668 173
B.5.5	Fax number	+441896 751 493
B.5.6	E-mail	Clinical-Trials@fk-b.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.3.2	Product code	FKB327
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	ADALIMUMAB
D.3.9.1	CAS number	331731-18-1
D.3.9.2	Current sponsor code	FKB327
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	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.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 INC
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Humira
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	ADALIMUMAB
D.3.9.1	CAS number	331731-18-1
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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Rheumatoid Arthritis

E.1.1.1

Medical condition in easily understood language

Rheumatoid Arthritis

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	18.1
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 of this study is to assess the efficacy of FKB327 compared with Humira®, when each is administered in combination with methotrexate.

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are as follows:
_ To compare the safety profiles of FKB327 and Humira, each in combination with methotrexate treatment.
_ To assess the efficacy profiles of FKB327 and Humira over time, including initial onset of effect.
_ To compare the proportions of patients on FKB327 and Humira, who develop anti drug antibodies (ADAs) and to summarise the distribution of the level of ADA activity between patients on FKB327 and Humira.
_ To compare the steady state pharmacokinetics of FKB327 and Humira administered by multiple dosing in patients with RA receiving concomitant treatment with methotrexate.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

_ Men or women aged ≥ 18 years.
_ RA, diagnosed to revised American College of Rheumatology (ACR) criteria (2010 version) at least 3 months prior to Screening.
_ Active RA, as confirmed by ≥6 tender and ≥6 swollen joint counts out
of 68/66, respectively, at Screening and at Baseline.
_ C-reactive protein (CRP) level ≥10 mg/L at Screening.
_ Taking MTX (oral or parenteral) for at least 3 months prior to
Screening and at a stable dose of between 10 and 25 mg/week for at
least 8 weeks, with concomitant folic/folinic acid of at least 5 mg/week.
Patients can start treatment with folic acid at Screening if not already
receiving it.

E.4

Principal exclusion criteria

Patients will be excluded from the study if any of the following exclusion criteria are met (list not comprehensive):
_ Prior treatment with adalimumab.
_ Prior treatment with more than 1 biologic or 1 protein kinase inhibitor
DMARD for RA.
_ Prior treatment with TNF inhibitors for RA with lack of efficacy.
_ Prior treatment with cyclophosphamide.
_ Treatment with an investigational agent within 12 weeks or 5 halflives
of the drug.
_ Immunisation with a live or attenuated vaccine within 4 weeks prior to
study drug dosing.
_ Intra-articular or parenteral steroids within 28 days prior to Screening.
_ Treatment with any DMARDs, other than MTX.
_ History of relevant allergy/hypersensitivity to monoclonal antibodies
or any of the excipients of FKB327 or Humira, or history of clinically
significant contact allergy/hypersensitivity to latex or rubber.
_ Presence of active autoimmune disease or joint disease other than RA
(eg, mixed connective tissue disorder, gout) which may confound
efficacy assessments such as joint count evaluations or CRP/erythrocyte
sedimentation rate (ESR).
_ ACR functional Class IV.
_ Major surgery within 8 weeks prior to Screening or planned to take
place during the study period.
_ Presence of chronic or acute infection at Screening including positive
result for human immunodeficiency virus (HIV) 1 or 2, hepatitis B (HBV),
hepatitis C (HCV), and active tuberculosis (TB) or untreated latent TB.
_ Acute infection requiring parenteral antibiotics within 4 weeks of study
dosing or requiring oral/topical antibiotics within 2 weeks of study
dosing.
_ Presence of serious, uncontrolled disease of another body system
including cardiovascular, neurological, pulmonary, renal and hepatic
disease.
_ Presence of New York Heart Association (NYHA) Class III/IV heart
failure.
_ Presence of any uncontrolled disease for which steroid treatment is
regularly required for flares.
_ Presence of any malignancy or history of malignancy in the 5 years.
_ Patients with demyelinating diseases.
_ Pregnant or breastfeeding women.
_ Patients with any condition or circumstances, which, in the opinion of
the Investigator, make them unsuitable for the study, unlikely or unable
to comply with study procedures and requirements.
_ Body weight >120 kg.
_ Prior or current treatment with an agent which might confound
efficacy or safety evaluation in this study, eg, RANKL inhibitors for
osteoporosis, immunomodulators for asthma within 5 half-lives of the
drug concerned prior to the first dose of study treatment.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the ACR20 response rate.

E.5.1.1

Timepoint(s) of evaluation of this end point

The ACR20 response rate is evaluated at Week 24.

E.5.2

Secondary end point(s)

The key secondary efficacy endpoint is as follows:
_ DAS28-CRP score.

Other secondary efficacy endpoints are as follows:
_ ACR20, ACR50 and ACR70 response rates.
_ Values of the individual ACR core set variables (swollen joint count, tender joint count, CRP, patient’s assessment of disease activity, physician’s assessment of disease activity, patient’s assessment of pain, Health Assessment Questionnaire Disability Index [HAQ DI]) .
_ DAS28-CRP score and change in DAS28-CRP score .
_ DAS28 score based on erythrocyte sedimentation rate (DAS28-ESR).

E.5.2.1

Timepoint(s) of evaluation of this end point

_ DAS28-CRP score is evaluated at Week 24.
_ ACR20, ACR50 and ACR70 response rates are evaluated over time.
_ Values of the individual ACR core set variables are evaluated over time.
_ DAS28-CRP score and change in DAS28-CRP score are evaluated over time.
_ DAS28 score is evaluated at Weeks 12 and 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

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

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

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

Bulgaria

Canada

Chile

Czech Republic

Germany

Peru

Poland

Romania

Russian Federation

Serbia

Spain

Ukraine

United States

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

LVLS

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:

622

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

108

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

350

F.4.2.2

In the whole clinical trial

730

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)

Either end of study (none) or inclusion in the open-label extension (study FKB327-003)

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

2015-01-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-11-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-07-12

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