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.

• Register: EUCTR
• Last refreshed on: 4 January 2022
• Main ID: EUCTR2016-002269-77-DE
• Date of registration: 28/04/2017
• Prospective Registration: Yes
• Primary sponsor: Bristol-Myers Squibb International Corporation
• Public title: 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.
• Scientific title: 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)
• Date of first enrolment: 07/08/2017
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002269-77
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Double-Blind (24 wks), followed by an Open Label (28 wks), followed by Open Label Ext (3 yrs); If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Brazil, Czech Republic, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Mexico, Sweden, United States

Contacts

• Name: GCT-SU
• Affiliation: Bristol-Myers Squibb International Corporation

• Name: GCT-SU
• Affiliation: Bristol-Myers Squibb International Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
a) Diagnosis of Definite or Probable IIM (DM or PM) based on Bohan and Peter classification criteria
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) or a prior muscle biopsy diagnostic for IIM or a positive test for at least one myositis-specific autoantibody
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 myositisspecific autoantibody (anti-aminoacyl-tRNA synthetases (Jo-1, PL-7, PL-12, EJ, OJ, KS, Zo, YRS), anti-Mi-2, anti-SRP, anti-TIF1-?, 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 3 months 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, mycophenolate 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 stable dose of 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

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 6 months prior to randomization (there must be laboratory results indicating the presence of circulating B cells (CD19+). Any other biologic treatment in the past 3 months or immune globuline (intravenous [IVIG] or subcutaneous [SCIG] in the past 3 months prior to randomization.
d) Subjects with uncontrolled or rapidly progressive interstitial lung disease
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-TIF1-? (p155/140)
autoantibody prior to randomization who were diagnosed with IIM < 1
year prior to randomization.
h) Subjects with history of chronic or recurrent bacterial, viral or systemic fungal infections
i) 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 recommendations for malignancy are outlined in Sections 3.3.2 and 3.3.4.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Idiopathic Inflammatory Myopathy (IIM; eg, Dermatomyositis [DM], Polymyositis [PM], autoimmune necrotizing myopathy)
MedDRA version: 20.0 Level: LLT Classification code 10042753 Term: Symptomatic inflammatory myopathy System Organ Class: 100000004859

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Trade Name: Orencia
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ABATACEPT
CAS Number: 332348-12-6
Current Sponsor code: BMS-188667
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: 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 24.
- Assessing the mean change in functional disability using the Health Assessment Questionnaire-Disability Index (HAQ-DI) from baseline to Week 24.
- Assessing the mean change in extra-muscular disease activity as defined by Myositis Disease Activity Assessment Tool (MDAAT) from baseline to 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 24.

Timepoint(s) of evaluation of this end point: Week 24

Main Objective: 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%

Primary end point(s): Proportion of subjects who achieve IMACS DOI at Week 24 without rescue

Secondary Outcome(s)

Secondary end point(s): - Mean change in muscle endurance using the myositis function index (FI-2) from baseline to Day 169 (Week 24)
- Mean change in Health Assessment Questionnaire-Disability Index (HAQ-DI) from baseline to Day 169 (Week 24)
- Mean change in Myositis Disease Activity Assessment Tool (MDAAT) from baseline to Day 169 (Week 24)
- Mean change in Myositis Response Criteria score from baseline to Day 169 (Week 24)

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

Timepoint(s) of evaluation of this end point: Week 24

Secondary ID(s)

IM101611

Source(s) of Monetary Support

Bristol-Myers Squibb International Corporation

Ethics review

Status: Approved
Approval date: 07/08/2017
Contact: