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Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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EUCTR |
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Last refreshed on:
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8 October 2021 |
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Main ID: |
EUCTR2005-004575-37-FR |
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Date of registration:
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26/03/2007 |
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Prospective Registration:
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Yes |
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Primary sponsor: |
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Public title:
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A Sequential Adaptive Phase II/III Multi-Center, Randomized, Double-Blind, Placebo-
Controlled Study to Evaluate the Efficacy and Safety of Abatacept Versus Placebo on a Background of Mycophenolate Mofetil and Glucocorticosteroids in Subjects with Active Proliferative Glomerulonephritis Due to Systemic Lupus Erythematosus (SLE).
And Pharmacogenetics Blood Sample Amendment Number 1 - Site Specific (Version 2.0, Date 19-Jan-07).
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Scientific title:
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A Sequential Adaptive Phase II/III Multi-Center, Randomized, Double-Blind, Placebo-
Controlled Study to Evaluate the Efficacy and Safety of Abatacept Versus Placebo on a Background of Mycophenolate Mofetil and Glucocorticosteroids in Subjects with Active Proliferative Glomerulonephritis Due to Systemic Lupus Erythematosus (SLE).
And Pharmacogenetics Blood Sample Amendment Number 1 - Site Specific (Version 2.0, Date 19-Jan-07). |
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Date of first enrolment:
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27/04/2007 |
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Target sample size:
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460 |
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Recruitment status: |
Not Recruiting |
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URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-004575-37 |
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Study type:
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Interventional clinical trial of medicinal product |
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Study design:
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Controlled: yes
Randomised: yes
Open: no
Single blind: no
Double blind: yes
Parallel group: no
Cross over: no
Other: yes
Other trial design description: Open Label extension after double blind study period
If controlled, specify comparator, Other Medicinial Product: no
Placebo: yes
Other: no
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): yes
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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Belgium
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France
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United Kingdom
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Contacts
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Key inclusion & exclusion criteria
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Inclusion criteria:
1) Signed written informed consent
2) SLE as defined by meeting at least 4 of the 11 classification criteria of the American College of Rheumatology for the classification of Systemic Lupus Erythematosus (Protocol Appendix 1), either sequentially or coincidentally. The 4 criteria need not be present at the time of study entry.
3) Biopsy within 6 months of enrollment (screening visit) indicating active proliferative
lupus glomerulonephritis ISN/RPS 2003 classification Class III or IV [excluding Class III (C), IV-S (C) and IV-G (C)]. If renal function has deteriorated, biopsy may have been no more than 3 months prior to enrollment (screening visit).
4) Active renal disease at the screening visit, as defined by:
urinary protein/creatinine ratio = 50 mg/mmol AND an active urinary sediment as defined by at least one of the following 3 criteria:
a) > 5 RBC/hpf OR
b) > 8 WBC/hpf (with no evidence of a urinary tract infection) OR
c) cylindruria
5) Serum creatinine = 3 mg/dL. (Subjects not meeting this criterion but meeting all other inclusion and exclusion criteria may be re-screened for serum creatinine ONCE
within 2 weeks of the original screening visit in consultation with the BMS Medical
Monitor).
6) Men and women, at least 18 years of age.
7) Eligibility of subjects for entry into the study is based on their current renal disease activity which may represent:
a) The first manifestation of their SLE.
b) The first renal manifestation of SLE.
c) Recent worsening of glomerulonephritis that had been diagnosed previously.
d) Persistence of renal disease despite current therapies, including MMF and/or
glucocorticosteroids, as long as the medications used are permitted by protocol.
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 unwilling or unable to use an acceptable method to avoid pregnancy for entire study period & up to 10 weeks after study
2)WOCBP using a prohibited contraceptive method (there are none)
3)pregnant or breastfeeding women
4)Women with positive pregnancy test on enrollment or prior to study drug
administration
5)Males unwilling or unable to follow recommendations for use of contraception
specified by the manufacturer of any protocol-permitted disease sparing medication
(biologic or non-biologic) being used during study
6)Subjects with a rise of serum creatinine of = 1 mg/dL within 1 month prior to screening visit
7)Subjects with drug-induced SLE, as opposed to idiopathic SLE.
8)Subjects with severe, unstable &/or progressive CNS lupus (screening MRI or other imaging of the brain is not required to rule-out CNS disease in subjects who have no clinical features suggesting active CNS disease)
9)Subjects with autoimmune disease other than SLE as their main diagnosis (e.g.; RA, MS)
10)Current symptoms of severe, progressive, or uncontrolled non-SLE related renal,
hepatic, hematological, gastrointestinal, pulmonary, cardiovascular, neurological,
endocrine, or cerebral disease. Concomitant medical conditions that, in the opinion of
the Investigator, might place the subject at unacceptable risk for participation in this
study
11)Concomitant illness that in the opinion of the investigator, is likely to require
additional high dose oral glucocorticosteroid therapy (i.e. > 45 mg per day) during study, (e.g.; asthma)
12)Female subjects who have had breast cancer screening study suspicious for malignancy, & in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations
13)Female subjects who have evidence of cervical dysplasia unless treated with
definitive therapy
14)history of cancer within last 5 years (other than non-melanoma skin cell (NMSC) cancers cured by local resection). Existing NMSC cancers must be removed prior to randomization (Day 1 treatment). Subjects with carcinoma in situ, treated with definitive surgical intervention, are allowed
15)any serious bacterial infection within last 3 months, unless treated & resolved with antibiotics, or any chronic bacterial infection (such as chronic pyelonephritis, osteomyelitis & bronchiectasis)
16)Subjects at risk for tuberculosis. Specifically subjects with:
a)Current clinical, radiographic or laboratory evidence of active TB
b)history of active TB within last 3 years even if treated
c)history of active TB > 3 years ago unless there is documentation that
the prior anti-TB treatment was appropriate in duration & type
d)Latent TB which has not been successfully treated
17)Subjects with herpes zoster that resolved < 2 months prior to screening visit
18)Subjects with evidence (as assessed by the Investigator) of active or latent bacterial or viral infections at time of potential enrollment, including subjects with evidence of HIV infection
19)renal transplant recipients or candidates
20)Subjects who are diagnosed as end-stage renal disease
21)persistent non-lupus related pyuria
22)a degree of tubulo-interstitial changes that suggest an irreversible
decrease in renal function
23) Subjects currently on hydroxychloroquine or chloroquine with evidence of
retinopathy within 6 months of screening visit. If local standards for routine
ophthalmologic follow-up suggest such formal examinations are needed subjects who ha
Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
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Health Condition(s) or Problem(s) studied
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IMMUNOSUPPRESSION FOR DISEASE, NOS
MedDRA version: 9.1
Level: LLT
Classification code 10025139
Term: Lupus erythematosus systemic
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Intervention(s)
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Product Name: Abatacept
Product Code: BMS-188667
Pharmaceutical Form: Powder for solution for injection
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 injection
Route of administration of the placebo: Intravenous use
Trade Name: CellCept
Product Name: mycophenolate mofetil
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: mycophenolate mofetil
CAS Number: 24280-93-1
Current Sponsor code: MMF
Other descriptive name: CellCept
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
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Primary Outcome(s)
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Main Objective: *Double-Blind (DB) Period:
The primary objective of this adaptive design study is to compare a single abatacept
regimen versus placebo on a background of MMF plus glucocorticosteroids using the
posterior probability of superiority over placebo in the time to achieving protocol-defined complete renal response of lupus glomerulonephritis (defined in Protocol Section 3.3.1.1) during this 12 month double-blind study.
*Open-Label (OL) Extension Phase:
Assess the long-term clinical safety and tolerability of abatacept treatment during the
Open-Label Extension Phase.
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Secondary Objective: *DB:
Compare:
1)time to achieving protocol-defined complete renal response of lupus glomerulonephritis (Protocol Section 3.3.1.1) during this 12 month DB study of an abatacept regimen vs placebo on a background of MMF + glucocorticosteroids using the classical Cox proportional hazards model
2)proportion of subjects achieving complete renal response of lupus glomerulonephritis during the 12 months between abatacept & placebo regimens
3)proportion of subjects with a complete renal response who maintain complete renal response for at least 3 months between abatacept & placebo regimens
4)time to achieving Renal Improvement (Protocol Section 3.3.1.2); or together the
criteria Complete Renal Response & Renal Improvement
between abatacept & placebo regimens
Refer to protocol section 2.2 for additional DB phase Sec. Objectives
*OL:
Assess durability of efficacy (e.g. complete renal response, renal improvement,
SLICC/ACR Damage Index), immunogenicity & corticosteroid use
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Primary end point(s): The primary efficacy endpoint is the time to complete renal response as defined
by this protocol. The proportion of subjects experiencing a complete renal response or renal improvement during the 12 months will be secondary endpoints.
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Source(s) of Monetary Support
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Ethics review
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Status: Approved
Approval date: 19/04/2007
Contact:
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