Clinical Trials Register

Summary
EudraCT Number:	2008-001523-57
Sponsor's Protocol Code Number:	IM101179
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-10-22
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

UK - MHRA

A.2

EudraCT number

2008-001523-57

A.3

Full title of the trial

Multicenter, Open-Label Study to Assess Early Response to Abatacept with Background Methotrexate Using Power Doppler Ultrasonography in Patients with Active Rheumatoid Arthritis and Inadequate Response to Methotrexate

A.4.1

Sponsor's protocol code number

IM101179

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	Bristol Myers Squibb International Corporation
B.1.3.4	Country	Belgium
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	Orencia
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Company
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	Abatacept (IV)
D.3.2	Product code	BMS-188667
D.3.4	Pharmaceutical form	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Abatacept
D.3.9.1	CAS number	332348-12-6
D.3.9.2	Current sponsor code	BMS-188667
D.3.9.3	Other descriptive name	CTLA4Ig
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	250
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	Fusion protein

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

Adult subjects with active rheumatoid arthritis (RA) according to the American Rheumatism Association criteria for the classification of RA and with inadequate response to methotrexate

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	10039073
E.1.2	Term	Rheumatoid arthritis

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 main objective is to assess the occurrence of early signs of response to abatacept with background methotrexate, as defined by improvement of synovitis measured by Power Doppler Ultrasonography of the affected metacarpophalangeal joints (2-5th MCPs only) during the study in subjects with active rheumatoid arthritis and inadequate response to methotrexate.

E.2.2

Secondary objectives of the trial

The second objective is to estimate the predictability of the global PDUS score or its components of the synovitis level of the 2-5th MCP joints to disease activity measured by DAS28-CRP or DAS28-CRP-derived criteria at specified timepoints during the study.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1)Subjects must meet the 1987 criteria of the American Rheumatism Association
for the classification of RA
2) Subjects must have had a diagnosis of RA for more than 6 months from the time
of the initial diagnosis of RA.
3) Subjects must have disease activity defined by a DAS28-CRP > 3.2, or all of the following criteria must be met: tender joint count of ≥ 6, a swollen joint count of ≥ 6, and a C-reactive protein (CRP) measurement greater than the upper limit of normal (ULN).
4) Subjects must have a total synovitis PDUS score >1 for at least 2 MCPs (MCP2-5) and a total synovitis PDUS score >1 for at least one other MCP (MCP2-5) at the
screening visit and at the baseline (Day 1, before infusion) visit.
5) Subjects must have been treated with methotrexate of at least 15 mg for at least
3 months before Day 1 and on a stable dose for the last 28 days before Day 1. In subjects with intolerance to methotrexate, the dose could be reduced to a maximum tolerated dose (ie, 10 mg weekly) for at least 3 months before Day 1 and on a stable dose for the last 28 days before Day 1.
6) Subjects who received combination therapy (methotrexate plus another
nonbiologic DMARD) before study entry require washout. These subjects must
not be treated with any background nonbiologic DMARD other than methotrexate
for at least 28 days before treatment (Day 1). In the case of leflunomide, the
washout period is 8 weeks unless subjects take cholestyramine according to the
manufacturer’s recommendation.
7) Subjects who have received oral corticosteroids during the 28 days before
treatment (Day 1) must have been on a stable dose for at least 25 out of 28 days
and on a total dose of ≤ the equivalent of 10 mg prednisone/day (see Section 5.5.1.2 of the protocol).
8) Subjects must be naive to treatment with biologic DMARDs (infliximab,
anakinra, etanercept, adalimumab, rituximab, tocilizumab, golimumab, certolizumab and any investigational biologic DMARD).

E.4

Principal exclusion criteria

1)Subjects who are impaired, incapacitated, or incapable of completing studyrelated
assessments.
2) Subjects who meet all diagnostic criteria for any other rheumatic disease (eg,
lupus erythematous).
3) Subjects who underwent previous MCP arthroplasty, have such a procedure
scheduled, or anticipate the need for such a procedure during the study. Subjects with other underjoint arthroplasties, other than MCPs are allowed in the study.
4) Subjects with active vasculitis of a major organ system, with the exception of
rheumatoid nodules.
5) Subjects with current symptoms of severe, progressive, or uncontrolled renal,
hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurologic, or cerebral disease, whether or not related to RA and which, in the opinion of the
investigator, might place a subject at unacceptable risk for participation in the
study.
6) Female subjects who have had a breast cancer screening that is suspicious for
malignancy and in whom the possibility of malignancy cannot be reasonably
excluded by additional clinical, laboratory, or other diagnostic evaluations
7) Subjects with a history of cancer in the last 5 years, other than non-melanoma
skin cell cancers cured by local resection or carcinoma in situ. Existing nonmelanoma
skin cell cancers should be removed, the lesion site healed and residual
cancer ruled out before administration of the study drug.
8) Subjects who clinically, significantly abuse drugs or alcohol.
9) Subjects with evidence (as assessed by the investigator) of active or latent
bacterial or viral infections at the time of potential enrollment, including subjects
with evidence of human immunodeficiency virus (HIV).
10) Subjects with herpes zoster or cytomegalovirus (CMV) that resolved less than
2 months before the informed consent document was signed.
11) Subjects who have received any live vaccines within 3 months of the anticipated
first dose of study medication.
12) Subjects with any serious bacterial infection within the last 3 months, unless
treated and resolved with antibiotics, or any chronic bacterial infection (eg,
chronic pyelonephritis, osteomyelitis or bronchiectasis).
13) Subjects at risk for tuberculosis (TB). Specifically excluded from this study will
be subjects with:
• A history of active TB within the last 3 years, even if it was treated.
• A history of active TB greater than 3 years ago, unless there is
documentation that the prior anti-TB treatment was appropriate in duration
and type.
• Current clinical, radiographic, or laboratory evidence of active TB.
• Latent TB that was not successfully treated (≥ 4 weeks).
14) Subjects must not be positive for hepatitis B surface antigen.
15) Subjects who are positive for hepatitis C antibody if the presence of hepatitis C
virus was also shown with polymerase chain reaction or recombinant immunoblot
assay.
16) Subjects with any of the following laboratory values
• Hemoglobin < 8.5 g/dL
• WBC < 3000/mm3 (< 3 x 109/L)
• Platelets < 100,000/mm3 (< 100 x 109/L)
• Serum creatinine > 2 times the ULN
• Serum ALT or AST > 2 times the ULN
17) Any other laboratory test results that, in the opinion of the investigator, might
place a subject at unacceptable risk for participation in the study.
18) Subjects who have at any time received treatment with any investigational drug
within 28 days (or less than 5 terminal half-lives of elimination) of the Day 1
dose.
19) Subjects who have at any time received treatment with abatacept (BMS-188667
or CTLA4Ig).
20) Subjects who received an intra-articular injection of corticosteroids in the MCP joints within the last 3 months of Day 1 (before first infusion of abatacept).
21)Women who are pregnant or breastfeeding.
22) Women with a positive pregnancy test on enrollment or before administration of
abatacept.

E.5 End points

E.5.1

Primary end point(s)

Study Assessments and Primary Endpoints:
• Efficacy and safety parameters will be assessed at each predefined timepoint: Days 1, 7, 15, 29,
43, 57, 85, 113, 141, 169, and 199.
• Primary efficacy assessments consist of Power Doppler Ultrasonography (PDUS) MCP joint
assessments and the DAS28-CRP. The global PDUS score and DAS28-CRP will be calculated at
all visits during 6 months of treatment.
• Safety will be assessed throughout the study via physical examinations; monitoring of vital signs,
adverse events, and serious adverse events; pregnancy tests; and blood chemistry and hematology
analyses.

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

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

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

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

F.1.1.1

In Utero

Information not present in EudraCT

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

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

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

100

F.4.2.2

In the whole clinical trial

100

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)

When the research study stops the investigator will discuss with the patient options for their continued treatment and care. As abatacept is a marketed drug there will be an option for patients to continue this treatment if the patient is responding well and the study doctor feels the patients will benefit further from this.

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

2008-10-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-01-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-10-28

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