Ignite Creation Date:
2024-05-05 @ 9:12 PM
Last Modification Date:
2024-10-26 @ 10:00 AM
Study NCT ID:
NCT00832585
Status:
COMPLETED
Last Update Posted:
2011-03-10
First Post:
2009-01-28
Brief Title:
Study to Evaluate the Safety and Efficacy of Alefacept Amevive in Subjects With Moderate to Severe Atopic Dermatitis
Sponsor:
Rush University Medical Center
Organization:
Rush University Medical Center
Study Overview
Official Title:
A Phase IV Open Label Study to Evaluate the Safety and Efficacy of Intramuscular IM Alefacept Amevive 15mgwk in Subjects 18 Years and Older With Moderate to Severe Atopic Dermatitis
Status:
COMPLETED
Status Verified Date:
2011-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will assess the safety tolerability and efficacy of Alefacept in patient with moderate to severe atopic dermatitis who could not be adequately controlled with topical therapies
Detailed Description:
Atopic dermatitis is a chronic inflammatory skin disease associated with cutaneous hyper-reactivity to environmental triggers that are generally innocuous to healthy nonatopic individuals Leung et al 2004 Acute eczematous skin lesions in atopic dermatitis are characterized by marked epidermal intercellular edema spongiosis Chronic lesions are characterized by an acanthotic epidermis with elongation of the rete ridges parakeratosis and minimal spongiosis Leung and Bieber 2003
A significant mixed inflammatory cell infiltrate is present in both acute and chronic skin lesions consisting of lymphocytes immunoglobulin E IgE-bearing Langerhans cells inflammatory dendritic epidermal cells and macrophages Eosinophils are also present in varying levels Leung and Bieber 2003
Activation and skin-selective homing of peripheral blood T lymphocytes and their subsequent effector functions in the skin represent sequential immunologic events in the pathogenesis of atopic dermatitis Akdis et al 2000 More than 90 of skin-infiltrating T lymphocytes in inflammatory skin diseases such as atopic dermatitis express CD44- and the oligosaccharide determinant cutaneous lymphocyte-associated antigen CLA Berg et al 1991 The migration of CD4 CLA-positive T lymphocytes across cytokine-activated endothelial cell layers has 2 been shown to be dependent on the interaction of lymphocyte function-associated antigen LFA-1 and intercellular adhesion molecule ICAM-1 Santamaria Babi et al 1995
The activation of T lymphocytes plays an important role in atopic dermatitis pathogenesis In acute atopic dermatitis a T-helper TH2 cytokine profile is predominantly seen with increased expression of interleukin IL-4 lL-5 and IL-13 Stone 2003 In chronic atopic dermatitis the cytokine profile changes to a TH1 predominant profile with increased expression of interferon y IFN-y Leung et al 2004 Activated T lymphocytes also are responsible for direct cell-mediated keratinocyte apoptosis which contributes to the spongiosis pattern of epidermal injury characteristic of acute atopic dermatitis Trautmann et al 2001
The interaction of T lymphocytes with antigen-presenting cells APCs is one of the initial steps in T lymphocyte activation of an immunologic response to what is perceived by the immune system to be a foreign antigen Although much attention has been focused on the primary interaction of the T lymphocyte receptor with the major histocompatability complex MHC-antigen complex on the APC several other cell surface components are also involved in and necessary for T lymphocyte activation Ligand pairs necessary for T lymphocyte activation located on the cell surface of the T lymphocytes and the APC respectively include CD2LFA-3 LFA-1ICAM-1 also ICAM-2 and ICAM-3 CD281B7 CD4MHC Class II and CD8MHC Class I CD2 interaction with LFA-3 is necessary for T lymphocyte activation binding and T-helper cell responses Fischer et al 1986 Springer et al 1987
Anievive Alefacept is a dimeric fusion protein that consists of the extracellular CD2 binding portion of the human leukocyte function antigen -3 LFA-3 linked to the Fc portion of IgG1 Amevive interferes with lymphocyte activation by specifically binding to CD2 on lymphocytes thereby inhibiting LFA-3CD2 interaction Amevive causes a reduction in CD4 lymphocytes which play a role in atopic dermatitis Currently Amevive has been shown to be a safe and effective agent in the treatment of psoriasis but may prove useful in treating atopic dermatitis Unlike other biologics for the treatment of skin diseases the use of alefacept is not associated with increased infection congestive heart failure demyelinating disorders or lupus- like syndromes 1-Lodak and David 2004
Ten atopic patients who meet the inclusionexclusion criteria will be enrolled in the study
A significant mixed inflammatory cell infiltrate is present in both acute and chronic skin lesions consisting of lymphocytes immunoglobulin E IgE-bearing Langerhans cells inflammatory dendritic epidermal cells and macrophages Eosinophils are also present in varying levels Leung and Bieber 2003
Activation and skin-selective homing of peripheral blood T lymphocytes and their subsequent effector functions in the skin represent sequential immunologic events in the pathogenesis of atopic dermatitis Akdis et al 2000 More than 90 of skin-infiltrating T lymphocytes in inflammatory skin diseases such as atopic dermatitis express CD44- and the oligosaccharide determinant cutaneous lymphocyte-associated antigen CLA Berg et al 1991 The migration of CD4 CLA-positive T lymphocytes across cytokine-activated endothelial cell layers has 2 been shown to be dependent on the interaction of lymphocyte function-associated antigen LFA-1 and intercellular adhesion molecule ICAM-1 Santamaria Babi et al 1995
The activation of T lymphocytes plays an important role in atopic dermatitis pathogenesis In acute atopic dermatitis a T-helper TH2 cytokine profile is predominantly seen with increased expression of interleukin IL-4 lL-5 and IL-13 Stone 2003 In chronic atopic dermatitis the cytokine profile changes to a TH1 predominant profile with increased expression of interferon y IFN-y Leung et al 2004 Activated T lymphocytes also are responsible for direct cell-mediated keratinocyte apoptosis which contributes to the spongiosis pattern of epidermal injury characteristic of acute atopic dermatitis Trautmann et al 2001
The interaction of T lymphocytes with antigen-presenting cells APCs is one of the initial steps in T lymphocyte activation of an immunologic response to what is perceived by the immune system to be a foreign antigen Although much attention has been focused on the primary interaction of the T lymphocyte receptor with the major histocompatability complex MHC-antigen complex on the APC several other cell surface components are also involved in and necessary for T lymphocyte activation Ligand pairs necessary for T lymphocyte activation located on the cell surface of the T lymphocytes and the APC respectively include CD2LFA-3 LFA-1ICAM-1 also ICAM-2 and ICAM-3 CD281B7 CD4MHC Class II and CD8MHC Class I CD2 interaction with LFA-3 is necessary for T lymphocyte activation binding and T-helper cell responses Fischer et al 1986 Springer et al 1987
Anievive Alefacept is a dimeric fusion protein that consists of the extracellular CD2 binding portion of the human leukocyte function antigen -3 LFA-3 linked to the Fc portion of IgG1 Amevive interferes with lymphocyte activation by specifically binding to CD2 on lymphocytes thereby inhibiting LFA-3CD2 interaction Amevive causes a reduction in CD4 lymphocytes which play a role in atopic dermatitis Currently Amevive has been shown to be a safe and effective agent in the treatment of psoriasis but may prove useful in treating atopic dermatitis Unlike other biologics for the treatment of skin diseases the use of alefacept is not associated with increased infection congestive heart failure demyelinating disorders or lupus- like syndromes 1-Lodak and David 2004
Ten atopic patients who meet the inclusionexclusion criteria will be enrolled in the study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None