A Phase IIIB Multi-center, Randomized, Double-Blind Study to Evaluate Remission and Joint Damage Progression in Methotrexate Naive Early Erosive RA Subjects Treated with Abatacept plus Methotrexate Compared with Methotrexate Revised Protocol 04, incorporating Protocol Amendments 05, 06, 08, 09 (V1.0 dated 18-Nov-2008) and Administrative Letter 02. Pharmacogenetics Amendment 1 dated 16-May-2005. Protocol Amendments 3 & 4 - Site Specific - dated 28-Dec-2005.

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2005-000784-26-GB
• Date of registration: 15/07/2005
• Prospective Registration: Yes
• Primary sponsor: Bristol Myers Squibb International Corporation
• Public title: A Phase IIIB Multi-center, Randomized, Double-Blind Study to Evaluate Remission and Joint Damage Progression in Methotrexate Naive Early Erosive RA Subjects Treated with Abatacept plus Methotrexate Compared with Methotrexate Revised Protocol 04, incorporating Protocol Amendments 05, 06, 08, 09 (V1.0 dated 18-Nov-2008) and Administrative Letter 02. Pharmacogenetics Amendment 1 dated 16-May-2005. Protocol Amendments 3 & 4 - Site Specific - dated 28-Dec-2005.
• Scientific title: A Phase IIIB Multi-center, Randomized, Double-Blind Study to Evaluate Remission and Joint Damage Progression in Methotrexate Naive Early Erosive RA Subjects Treated with Abatacept plus Methotrexate Compared with Methotrexate Revised Protocol 04, incorporating Protocol Amendments 05, 06, 08, 09 (V1.0 dated 18-Nov-2008) and Administrative Letter 02. Pharmacogenetics Amendment 1 dated 16-May-2005. Protocol Amendments 3 & 4 - Site Specific - dated 28-Dec-2005.
• Date of first enrolment: 25/11/2005
• Target sample size: 750
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-000784-26
• 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: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Czech Republic, Germany, Ireland, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1) Subject is willing to participate in the study and has signed the informed consent.
2) Males or females (not nursing and not pregnant) = 18 years of age. Males and
women of child-bearing potential are eligible if they are practicing effective
contraceptive measures.
3) Subjects must meet the criteria of the American Rheumatism Association (1987) for
the diagnosis of rheumatoid arthritis.
4) Subjects must have a diagnosis of RA less than or equal to 2 years.
5) Subjects must have high disease activity as defined by a tender joint count of at least 12, swollen joint count of at least 10, and a CRP of = .45 mg/dL or = 4.5 mg/L.
6) Subjects that are RF or anti-CCP positive.
7) Subjects must have evidence of erosion of the hands, wrists or feet on the screening radiograph. (To be read centrally)
8) Subjects must be methotrexate naive or their prior exposure must have been =10mg a week for not more than 3 weeks and no dose for 3 months prior to signing the informed consent.
9) Men and women (not nursing and not pregnant) = 18 years of age. Men and Women of childbearing potential are eligible if they are practicing effective contraceptive measures.
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity
25 IU/L or equivalent units of HCG) within 48 hours prior to the start of study
medication.
Male subjects must be using an adequate method of contraception throughout the study including up to 10 weeks after the last infusion of abatacept so that the risk of pregnancy to their partner is minimized.

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period and for up to 10 weeks after the last infusion of abatacept.
2) Subjects who are impaired, incapacitated, or incapable of completing study related
assessments.
3) Subjects who meet diagnostic criteria for any other rheumatic disease (e.g., lupus
erythematous).
4) Subjects who have previously received treatment with an approved or investigational biologic RA therapy (infliximab, etanercept, anakinra, adalimumab).
5) Subjects with active vasculitis of a major organ system with the exception of
rheumatoid nodules.
6) Subjects with current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease, or other medical conditions that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study.
7) Female subjects, who have not had age and/or risk factor appropriate breast cancer screening or who have had a breast cancer screening study that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations (Please refer to Section 7.3.2).
8) Subjects with a history of cancer within the last five years (other than non-melanoma skin cell cancers cured by local resection). Existing non-melanoma skin cell cancers must be removed prior to dosing.
9) Subjects who have clinically significant drug or alcohol abuse.
10) Subjects with any serious acute bacterial infection (such as pneumonia or
pyelonephritis) unless treated and completely resolved with antibiotics.
11) Subjects with severe chronic or recurrent bacterial infections (such as recurrent
pneumonia, chronic bronchiectasis).
12) The following subjects are excluded from this study:
- Subjects with current clinical or laboratory evidence of active or latent
tuberculosis (TB).
- Subjects with a history of active TB that was treated within the last 3 years.
- Subjects with 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.
13) Subjects with herpes zoster that resolved less than 2 months prior to enrollment.
14) 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) infection.
15) Subjects with Hepatitis B surface antigen.
16) Subjects with Hepatitis C antibody-positive subjects who are also RIBA-positive or PCR-positive.
17) Subjects with any of the following laboratory values:
- Hgb < 8.5 g/dL.
- WBC < 3,000/mm3 (3 x 109/L)
- Platelets < 100,000/mm3 (100 x 109/L).
- Serum creatinine > 2 times upper limit of normal.
- Serum ALT or AST > 2 times upper

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

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis, Nos

Intervention(s)

Trade Name: Orencia
Product Name: Abatacept
Product Code: BMS-188667
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Abatacept
CAS Number: 332348-12-6
Current Sponsor code: BMS-188667
Other descriptive name: CTLA4Ig
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: The co-primary objectives for this study will compare the clinical efficacy of abatacept
used in combination with methotrexate versus methotrexate alone on the following:
1) The proportion of subjects who achieve remission in 12 months of treatment
(Day 365), as defined by a DAS 28 score less than 2.6 and
2) Joint damage progression measured by radiographic evaluation using the
Genant-Modified Sharp total score at 12 months of treatment (Day 365).

Secondary Objective: 1) Compare proportion of subjects with an ACR50 response at month 12 (Day 365).
2) Compare proportion of subjects achieving major clinical response defined by
6 months of consecutive ACR 70 response at month 12 (Day 365).
3) Compare disease activity as measured by DAS 28 score at month 12 (Day 365).
4) Compare improvement in physical function using the HAQ disability index at
month 12 (Day 365) and assess improvement in physical function at month 24
(Day 729).
5) Compare inhibition of joint damage progression measured by radiographic
evaluation using the Genant-modified Sharp erosion, and joint space narrowing at
month 12 (Day 365).
6) Assess inhibition of joint damage progression measured by radiographic
evaluation using the Genant-modified Sharp erosion, joint space narrowing and total
score at month 24 (Day 729).
7) Determine safety and tolerability of abatacept in this subject population, including evaluation of immunogenicity of abatacept.

Primary end point(s): Efficacy:
Co-primary efficacy analysis include, in the order of sequential testing, comparisons
between abatacept in combination with methotrexate and a placebo control of
methotrexate alone in remission rate (EULAR defined DAS 28 remission) by 12 months (Day 365) and total Sharp scores using the Genant-modified Sharp method at 12 months (Day 365).
The co-primary efficacy analysis will be performed with the intent-to-treat (ITT) analysis population including all subjects randomized and treated. All subjects who prematurely discontinue the trial after receiving study medication will have missing data imputed as a DAS 28 remission non-responder at all scheduled protocol visits subsequent to the point of discontinuation. Missing annual radiographic data will be imputed with linear extrapolation for discontinued subjects having baseline radiographs and at least one of either Day 169 radiographs or discontinuation radiographs. Subjects with missing baseline radiographic data will be excluded from the primary radiographic analyses.
The DAS 28 is a continuous variable which is a composite of 4 variables: the number of tender joints out of 28 joints, the number of swollen joints out of 28 joints, CRP and subject assessment of disease activity measure on a visual analog scale.

Safety:
The evaluation of drug safety is based on clinical AEs, vital signs and laboratory
abnormalities reported during the study. All safety presentations will include subjects
who received at least one dose of study medication and will group subjects by treatment received.

Secondary ID(s)

IM101-023

Results

• Results available: Yes
• Date Posted: 02/04/2015
• Date Completed: 13/10/2009
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-000784-26/results