Atopic DermatitisPhase 4NCT00832585
Study to Evaluate the Safety and Efficacy of Alefacept (Amevive) in Subjects With Moderate to Severe Atopic Dermatitis
A Phase 4 study testing Alefacept in people with Atopic Dermatitis, run by Rush University Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atopic Dermatitis
- What is being tested?
- Alefacept
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2008to Oct 2009
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed Informed Consent Form(s)
- Age of l8 years or older
- A diagnosis of atopic dermatitis as determined by the diagnostic criteria for atopic dermatitis
- Disease severity of 3 or 4 (moderate or severe) as assessed by PGA rating (0-4 scale)
- Be a candidate for systemic therapy who cannot be adequately controlled (ie have a PGA assessment of 3 014) with topical therapies (Le., medium-to high-potency topical corticosteroids, tacrolimus, or pimecrolimus).
- For female subjects of childbearing potential, use of an acceptable method of contraception to prevent pregnancy and agreement to continue to practice an acceptable method of contraception for the duration of their participation in the study and for 3 months after the last dose of Alefacept
- Willingness to hold sun exposure reasonably constant and to avoid use of tanning booths or other ultraviolet (UV) light sources during the study
Who cannot join
- History of hypersensitivity to alefacept or any of its components
- History of illegal drug or alcohol abuse
- History of or ongoing uncontrolled bacterial, viral, fungal, or atypical mycobacterial infection
- History of eczema herpeticum within the 30 days prior to screening
- History of opportunistic infections (e.g., systemic fungal infections, parasites)
- History of hepatitis B or C virus
Show all 19Show fewer
- History of active tuberculosis (TB) or currently undergoing treatment for TB.
- Presence of history of malignancy within the past 5 years, including lymphoproliferative disorders. Subjects with a history of fully resolved basal cell or squamous cell skin cancer may be enrolled in the study
- Pregnant or lactating women
- Diagnosis of hepatic cirrhosis, regardless of cause or severity
- Hospital admission for cardiovascular or pulmonary disease within the year prior to screening, including hospitalization for asthma exacerbations
- Subjects admitted to the hospital for chest pain that was subsequently determined to be non-cardiac in origin may be enrolled
- History of clinically significant anemia
- WBC count <4000/pL or> 14,000/pL
- Use of experimental drugs or treatments within 30 days or 5 half-lives, whichever is longer, prior to the first dose of alefacept
- Use of a live virus or live bacteria vaccine in the 14 days prior to be the first dose of alefacept
- Any medical condition that, in the judgment of the investigator, would jeopardize the subject's safety following exposure to study drug or would significantly interfere with the subject's ability to comply with the provisions of this protocol
- Any subject whose baseline atopic dermatitis PGA rating has changed to 0, 1, or 2 (clear, almost clear, or mild) from a screening rating of 3,4, or 5 (moderate, severe, or very severe)
- -
Trial locations and contacts
1 site in 1 country.
United States1 site
Rush University Medical Center - Department of Dermatology
Chicago, Illinois, 60612
About this study
Official title: A Phase IV, Open Label Study to Evaluate the Safety and Efficacy of Intramuscular (IM) Alefacept (Amevive) 15mg/wk in Subjects 18 Years and Older With Moderate to Severe Atopic Dermatitis
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.
Read the 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 (TH)2 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 CD2/LFA-3, LFA-1/ICAM-1 (also ICAM-2 and ICAM-3), CD281B7, CD4/MHC Class II, and CD8/MHC 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-3/CD2 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 inclusion/exclusion criteria will be enrolled in the study.
- Conditions
- Atopic Dermatitis
- Being tested
- Alefacept
- Keywords
- Atopic, Dermatitis, chronic, skin
- Medical subject headings
- Dermatitis, Atopic, Dermatitis, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlefaceptDrug
Also called Amevive
Alefacept 15mg IM every week for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Alefacept | Experimental | Amevive® has been shown to be a safe and effective agent in the treatment of psoriasis but may prove useful in treating atopic dermatitis at a dose of 15mg IM every week for 12 weeks. 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. Receives: Drug: Alefacept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Eczema Area Severity Index (EASI) Score From Baseline (Week 1) to Week 16.
The Eczema Area Severity Index (EASI) measures erythema (E), infiltration (I), excoriation (Ex) and lichenification (L) using 0=none, 1=mild, 2=moderate, 3=severe. Head/neck, upper limbs, trunk, lower limbs are rated from 1 to 6 (0=no eruption, 1=1-9%, 2=10-29%, 3=30-49%, 4=50-69%, 5=70-89%, 6=90-100%). The proportional factor for the head/neck =.01, upper limbs=.02, trunk=.03 and lower limbs=.04. The algorithm for calculating the EASI is the sum of E+I+Ex+L multiplied by the area, multiplied by the proportional factor. The total score is the sum of the four body-region scores, max=72, min=0.
Measured: Week 1 to week 16
Secondary outcomes (1)
Change in Physician Global Assessment (PGA) Score From Baseline (Week 1) to Week 16.
The Physician Global Assessment (PGA) evaluates the overall severity of Atopic Dermatitis (AD) at a given time using a four point scale (0=clear, 0.5=clear to mild, 1=mild, 1.5=mild to moderate, 2=moderate, 2.5=moderate to severe, and 3=severe).
Measured: Week 1 to week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2009 (estimated)
- Study startJan 2008
- Primary completionSep 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Atopic DermatitisStudies of the same condition, open and under way.
- More trials run by Rush University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rush University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma US, Inc.
- Investigators
- Michael D. Tharp, MD, Principal investigator, Rush University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00832585
- Sponsor's protocol ID
- AC 07-001
- Status last verified
- Mar 2011
- First submitted
- 28 Jan 2009
- Last updated
- 10 Mar 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IV, Open Label Study to Evaluate the Safety and Efficacy of Intramuscular (IM) Alefacept (Amevive) 15mg/wk in Subjects 18 Years and Older With Moderate to Severe Atopic Dermatitis
- ClinicalTrials.gov ID
- NCT00832585
- Acronym / sponsor ID
- AC 07-001
- Conditions
- Atopic Dermatitis
- Keywords
- Atopic, Dermatitis, chronic, skin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Rush University Medical CenterUniversity, hospital or other
- Collaborators
- Astellas Pharma US, Inc.
- Study start
- Jan 2008
- Primary completion
- Sep 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 30 Jan 2009 (estimated)
- Results
- Posted 28 Jan 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 (TH)2 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 CD2/LFA-3, LFA-1/ICAM-1 (also ICAM-2 and ICAM-3), CD281B7, CD4/MHC Class II, and CD8/MHC 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-3/CD2 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 inclusion/exclusion criteria will be enrolled in the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Alefacept | Experimental | Drug: AlefaceptAmevive® has been shown to be a safe and effective agent in the treatment of psoriasis but may prove useful in treating atopic dermatitis at a dose of 15mg IM every week for 12 weeks. 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Signed Informed Consent Form(s)
- Age of l8 years or older
- A diagnosis of atopic dermatitis as determined by the diagnostic criteria for atopic dermatitis
- Disease severity of 3 or 4 (moderate or severe) as assessed by PGA rating (0-4 scale)
- Be a candidate for systemic therapy who cannot be adequately controlled (ie have a PGA assessment of 3 014) with topical therapies (Le., medium-to high-potency topical corticosteroids, tacrolimus, or pimecrolimus).
Key exclusion criteria (19 listed)
- History of hypersensitivity to alefacept or any of its components
- History of illegal drug or alcohol abuse
- History of or ongoing uncontrolled bacterial, viral, fungal, or atypical mycobacterial infection
- History of eczema herpeticum within the 30 days prior to screening
- History of opportunistic infections (e.g., systemic fungal infections, parasites)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlefaceptAlso: AmeviveAlefacept 15mg IM every week for 12 weeks | Drug | Alefacept |
Primary outcome
Change in Eczema Area Severity Index (EASI) Score From Baseline (Week 1) to Week 16.
Time frame: Week 1 to week 16
The Eczema Area Severity Index (EASI) measures erythema (E), infiltration (I), excoriation (Ex) and lichenification (L) using 0=none, 1=mild, 2=moderate, 3=severe. Head/neck, upper limbs, trunk, lower limbs are rated from 1 to 6 (0=no eruption, 1=1-9%, 2=10-29%, 3=30-49%, 4=50-69%, 5=70-89%, 6=90-100%). The proportional factor for the head/neck =.01, upper limbs=.02, trunk=.03 and lower limbs=.04. The algorithm for calculating the EASI is the sum of E+I+Ex+L multiplied by the area, multiplied by the proportional factor. The total score is the sum of the four body-region scores, max=72, min=0.
1 secondary outcome
Change in Physician Global Assessment (PGA) Score From Baseline (Week 1) to Week 16.
Time frame: Week 1 to week 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael D. Tharp, MD principal investigator
Rush University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Alefacept in people with Atopic Dermatitis, run by Rush University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jan 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Eczema Area Severity Index (EASI) Score From Baseline (Week 1) to Week 16. (time frame: Week 1 to week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2011.