Clinical Trials Register

Summary
EudraCT Number:	2016-002269-77
Sponsor's Protocol Code Number:	IM101611
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2017-05-18
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

Czechia - SUKL

A.2

EudraCT number

2016-002269-77

A.3

Full title of the trial

A Phase 3, Randomized, Double-Blind Clinical Trial to Evaluate the Efficacy and Safety of Abatacept SC with Standard Treatment Compared to Standard Treatment Alone in Improving Disease Activity in Adults with Active Idiopathic Inflammatory Myopathy (IIM)

Randomizovaná, dvojitě zaslepená klinická studie fáze 3 pro hodnocení účinnosti a bezpečnosti přípravku abatacept podávaného subkutánně v kombinaci se standardní léčbou ve srovnání se samostatnou standardní léčbou při zlepšení aktivity onemocnění u dospělých s aktivní idiopatickou zánětlivou myopatií (IIM)

A.3.1

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

A Phase 3 trial to evaluate the effectiveness and safety of Abatacept SC alongside standard treatment in comparison to standard treatment alone in improving disease activity in adults with active idiopathic inflammatory myopathy, a group of chronic autoimmune inflammatory diseases that affect skeletal muscle.

A.4.1

Sponsor's protocol code number

IM101611

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	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	Bristol-Myers Squibb International Corporation
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bristol-Myers Squibb International Corporation
B.5.2	Functional name of contact point	GCT-SU
B.5.3	Address:
B.5.3.1	Street Address	Parc de l'Alliance - Avenue de Finlande, 4
B.5.3.2	Town/ city	Braine-l'Alleud
B.5.3.3	Post code	1420
B.5.3.4	Country	Belgium
B.5.6	E-mail	clinical.trials@bms.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	Orencia
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Pharma EEIG
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 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	ABATACEPT
D.3.9.1	CAS number	332348-12-6
D.3.9.2	Current sponsor code	BMS-188667
D.3.9.4	EV Substance Code	SUB20635
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	125
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	Yes
D.3.11.13.1	Other medicinal product type	Fusion protein

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 in pre-filled syringe
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

Idiopathic Inflammatory Myopathy (IIM; eg, Dermatomyositis [DM], Polymyositis [PM], autoimmune necrotizing myopathy)

E.1.1.1

Medical condition in easily understood language

Autoimmune inflammatory disease, of unknown cause, which causes muscle weakness and low muscle endurance

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10042753
E.1.2	Term	Symptomatic inflammatory myopathy
E.1.2	System Organ Class	100000018885

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective for this study is to compare the clinical efficacy of weekly abatacept in combination with
standard treatment to standard treatment alone by assessing the percentage of subjects who achieve the International Myositis Assessment and Clinical Studies - definition of improvement (IMACS DOI) by Wk 24 compared to baseline, defined as:
- An improvement of ≥ 20% in 3 IMACS core measures, AND
- No more than 2 IMACS core measure scores worsen by ≥ 25%, AND
- Manual Muscle Test (MMT-8) may not decrease by ≥ 25%

E.2.2

Secondary objectives of the trial

To assess the clinical efficacy of weekly abatacept in combination with standard treatment to standard treatment alone by;
- Assessing the change in muscle endurance test using the Myositis Function Index (FI-2) from baseline to Week 12 and Week 24.
- Assessing the mean change in functional disability using the Health Assessment Questionnaire-Disability Index (HAQ-DI) from baseline to Week 12 and Week 24.
- Assessing the mean change in extra-muscular disease activity as defined by Myositis Disease Activity Assessment Tool (MDAAT) from baseline to Week 12 and Week 24.
To assess the efficacy of abatacept in combination with standard treatment to standard treatment alone in achieving improvement on the Myositis Response Criteria by assessing the mean change from baseline to Week 12 and Week 24.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

a) Diagnosis of Definite or Probable IIM (DM or PM) based on the Bohan and Peter classification criteria (outlined in Appendix 3 of the protocol)
i) Subjects with dermatomyositis (DM) must also have a confirmed myositis-associated rash (Gottron’s papules or a heliotrope rash preferably confirmed by skin biopsy) and 2 or more of the remaining 4 criteria.
ii) Subjects with a diagnosis of IIM other than DM include PM, autoimmune necrotizing myopathy, myositis in association with another connective tissue disease (overlap myositis) and juvenile myositis subjects above the age of 18. These subjects must have a prior muscle biopsy diagnostic for IIM or a positive test for at least one myositis-specific autoantibody (anti-aminoacyl-tRNA synthetases (Jo-1, PL-7, PL-12, EJ, OJ, KS, Zo, YRS), anti-Mi-2, anti-SRP, anti-TIF1-c, anti-NXP-2, anti-MDA5, anti-SAE, anti-HMGCR). For subjects with overlap myositis, the myositis must be the principal clinically active manifestation of their disease.
Where applicable, documentation of prior skin biopsy, muscle biopsy, and autoantibody results must be obtained and retained by the site.
b) Demonstrable muscle weakness measured by the MMT-8 of ≤ 135 units and any 3 of the following:
i) MMT-8 ≤ 125 units
ii) Physician’s global assessment (PGA) VAS ≥ 2 cm
iii) Subject’s global assessment (SGA) VAS ≥ 2 cm
iv) HAQ-DI ≥ 0.5
v) One or more muscle enzyme (CK, aldolase, LDH, AST, ALT) ≥ 1.3 times upper limit of normal (ULN)
vi) MDAAT Extramuscular Global Activity VAS ≥ 2 cm
c) Demonstration of currently active IIM will be determined by an adjudication committee unless the subject has any one of the following:
i. an active myositis-associated rash (Gottron’s papules or heliotrope rash), or
ii. a recent (within 1 month prior to signing informed consent) biopsy, magnetic resonance imaging (MRI) or electromyogram (EMG) demonstrating active disease, or
iii. an elevated CK > 5 times the upper limit of normal at screening with no alternate explanation or cause
d) Active disease despite adequate prior treatment experience with corticosteroids, immunosuppressants, or biologics as determined by the investigator
e) The subject must be on background standard treatment for IIM. The standard treatments that are allowed as background treatment for IIM includes:
i. Corticosteroids alone, or
ii. One of the following immunosuppressants: methotrexate, azathioprine, mycophenalate mofetil, tacrolimus, or cyclosporine (combinations of these treatments are not allowed), or
iii. A combination of corticosteroids and one of the above immunosuppressants
• If using corticosteroids for IIM, the subject must have been on corticosteroids for at least 12 weeks prior to randomization and a stable dose of corticosteroids for at least 4 weeks prior to randomization.
• If using immunosuppressants other than azathioprine, the subject must have been on a the same medication for at least 12 weeks and a stable dose for at least 4 weeks prior to randomization.
• If using azathioprine, the subject must have been on azathioprine for at least 24 weeks with a stable dose for at least 12 weeks prior to randomization.

E.4

Principal exclusion criteria

a) Subjects with Inclusion Body Myositis or myositis other than IIM, e.g. drug-induced myositis and PM associated with HIV.
b) Subjects treated with penicillamine or zidovudine in the past 3 months
c) Subjects treated with rituximab in the past year or any other biologic treatment or IVIG in the past 6 months.
d) Subjects with uncontrolled or rapidly progressive interstitial lung disease (at the discretion of the investigator)
e) Subjects with severe muscle damage (Myositis Damage Index > 7/10), permanent weakness due to a non-IIM cause, or myositis with cardiac involvement
f) Cancer-associated myositis (myositis diagnosed within 2 years of a diagnosis of cancer). See criteria (2i)
g) Subjects who are known to be positive for the anti-TIF-1 (p155/140) autoantibody prior to randomization who were diagnosed with IIM < 1 year prior to randomization.
h) Subjects at risk for tuberculosis
i) Subjects with recent acute infection requiring antibiotics
j) Subjects with history of chronic or recurrent bacterial or viral infections
k) Subjects with active systemic fungal infections (eg, histoplasmosis, blastomycosis, or coccidiomycosis)
l) Subjects who have a present malignancy or have had a previous malignancy within the last 5 years prior to screening (except for a documented history of cured non-metastatic squamous or basal cell skin carcinoma or cervical carcinoma in situ). Additional screening requirements for malignancy are outlined in Sections 3.3.2 and 3.3.4.

E.5 End points

E.5.1

Primary end point(s)

Proportion of subjects who achieve IMACS DOI at Week 24 without rescue

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 24

E.5.2

Secondary end point(s)

- Mean change in muscle endurance using the myositis function index (FI-2) from baseline to Weeks 12 and 24
- Mean change in Health Assessment Questionnaire-Disability Index (HAQ-DI) from baseline to Weeks 12 and 24
- Mean change in Myositis Disease Activity Assessment Tool (MDAAT) from baseline to Weeks 12 and 24
- Mean change in Myositis Response Criteria score from baseline to Weeks 12 and 24

Safety Endpoints
- All adverse events (AEs/SAEs)
- AEs of interest (serious infections, malignancies, injection site reactions, systemic reactions)
- Laboratory test abnormalities

E.5.2.1

Timepoint(s) of evaluation of this end point

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

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

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

Double-Blind period (day 1 - week 24) followed by Open Label period (week 24- Week 52)

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

Information not present in EudraCT

E.8.4

The trial involves multiple sites in the Member State concerned

Information not present in EudraCT

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Information not present in EudraCT

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

Australia

Brazil

Czech Republic

France

Germany

Hungary

Italy

Japan

Korea, Republic of

Mexico

Sweden

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

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:

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

In situations where consent cannot be given by subjects, their legally acceptable representatives (as per country guidelines) may give consent.

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

F.4.2.2

In the whole clinical trial

150

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)

At the conclusion of the study, participants who continue to demonstrate clinical benefit will be eligible to receive BMS supplied study treatment. Study treatment will be provided via an extension of the study, a rollover study requiring approval by responsible health authority and ethics committee or through another mechanism at the discretion of BMS. BMS reserves the right to terminate access to BMS supplied study treatment (see protocol section 3.2 for further details).

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

2017-07-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-06-07

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2022-08-02

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