Ignite Creation Date:
2024-05-05 @ 11:37 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00091741
Status:
COMPLETED
Last Update Posted:
2009-07-22
First Post:
2004-09-16
Brief Title:
Safety and Efficacy Study of Etanercept Enbrel on the Response Rate of HIV-infected Subjects
Sponsor:
Georgetown University
Organization:
Georgetown University
Study Overview
Official Title:
A Phase I Pilot Study to Evaluate Safety and Efficacy of Etanercept Enbrel on the Response Rate of HIV-infected Subjects Who Are in Virologic Failure and Who Have Failed to Respond to Standard Antiretroviral Therapy
Status:
COMPLETED
Status Verified Date:
2004-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of conducting this already-FDA approved Phase I clinical trial is to evaluate the safety and efficacy of etanercept Enbrel on the response rate in HIV-infected subjects who have failed to respond to conventional antiretroviral HAART therapy and for whom no alternative therapy exists The greatest challenge faced by HIV-treating clinicians today is the management of virologic failure and metabolic complications of anti-HIV treatment Treatment failure can occur because of non-compliance drug discontinuation lack of drug potency inadequate drug plasma concentration or drug resistance Of these drug resistance remains the single most important reason for virological failure and rapidly limits treatment options
Detailed Description:
I Background and Rationale
The greatest challenge faced by HIV-treating clinicians today is the management of virologic failure and metabolic complications of anti-HIV treatment Treatment failure can occur because of non-compliance drug discontinuation lack of drug potency inadequate drug plasma concentration or drug resistance Of these drug resistance remains the single most important reason for virological failure and rapidly limits treatment options Virus resistance to all three major antiretroviral drug classes is now being reported even in primary seroconverters Although highly-active antiretroviral ARV therapy HAART has led to a sharp decline in AIDS-related morbidity and mortality treatment failure is a common significant problem and as many as 50 of patients have detectable plasma HIV RNA despite being on combination ARV therapy Salvage therapy is the term commonly used to define the approach taken when previous anti-HIV treatments fail to achieve desired goals which include 1 undetectable viral load 2 CD4 cell levels below 200 cellsmm3 and 3 the prevention of HIV disease progression It is one of the most difficult situations to face as a patient and one of the most problematic challenges for health-care providers Although this state of treatment failure is sometimes euphemistically referred to as management of treatment-experienced patients many HIV positive patients having already exhausted the benefits of at least a few drug combinations think of their next regimen as salvage or rescue therapy Some physicians argue that due to cross-resistance among different drugs within the same class people with HIV infection have only one good shot at treating it and that any treatment regimen beyond the first is therefore salvage therapy Others see salvage therapy as literally the end of the line--when an individuals HIV has developed extensive resistance to all currently available treatments But most providers consider salvage therapy to be somewhere in between these extremes Data on salvage therapy mostly comes from anecdotal reports and retrospective cohort studies With a paucity of clinical trial data clinicians are often forced to prescribe unproven regimens based on what is anticipated about cross-resistance and drug interactions It is important therefore that new agents and new approaches continue to be developed as an increasing number of patients in practice have exhausted all treatment options
The rationale of this study is based upon the existing literature which indicates that many of the manifestations and subsequent clinical deterioration of HIV-infected individuals are related to the immune dysfunction seen in HIV disease many of which are caused by the overproduction of proinflammatory cytokines most notable of which is the excessive production of TNF-α It is further postulated that removal of this TNF-α by a commercially available TNF-α-binding medication ENBREL etanercept may provide therapeutic benefit for HIV-infected patients who have failed to respond to standard antiretroviral therapy
II Goal and Objectives
The purpose of the project is to assess the safety profile and efficacy of a soluble p75 tumor necrosis factor TNF receptor Fc fusion protein Enbrel Amgen etanercept Thousand Oaks CA ie anti TNF-α on the response rate of salvage patients who are in virologic failure and who have failed to respond to standard antiretroviral therapy
The protocol will evaluate
1 Changes in CD4 T-cell enumeration viral load and soluble immune activation markers in HIV-infected patients from baseline to week 24 following treatment with anti-TNF-α
2 Safety and tolerability of anti-TNF-α with respect to treatment-limiting symptoms and laboratory adverse events through week 24
The greatest challenge faced by HIV-treating clinicians today is the management of virologic failure and metabolic complications of anti-HIV treatment Treatment failure can occur because of non-compliance drug discontinuation lack of drug potency inadequate drug plasma concentration or drug resistance Of these drug resistance remains the single most important reason for virological failure and rapidly limits treatment options Virus resistance to all three major antiretroviral drug classes is now being reported even in primary seroconverters Although highly-active antiretroviral ARV therapy HAART has led to a sharp decline in AIDS-related morbidity and mortality treatment failure is a common significant problem and as many as 50 of patients have detectable plasma HIV RNA despite being on combination ARV therapy Salvage therapy is the term commonly used to define the approach taken when previous anti-HIV treatments fail to achieve desired goals which include 1 undetectable viral load 2 CD4 cell levels below 200 cellsmm3 and 3 the prevention of HIV disease progression It is one of the most difficult situations to face as a patient and one of the most problematic challenges for health-care providers Although this state of treatment failure is sometimes euphemistically referred to as management of treatment-experienced patients many HIV positive patients having already exhausted the benefits of at least a few drug combinations think of their next regimen as salvage or rescue therapy Some physicians argue that due to cross-resistance among different drugs within the same class people with HIV infection have only one good shot at treating it and that any treatment regimen beyond the first is therefore salvage therapy Others see salvage therapy as literally the end of the line--when an individuals HIV has developed extensive resistance to all currently available treatments But most providers consider salvage therapy to be somewhere in between these extremes Data on salvage therapy mostly comes from anecdotal reports and retrospective cohort studies With a paucity of clinical trial data clinicians are often forced to prescribe unproven regimens based on what is anticipated about cross-resistance and drug interactions It is important therefore that new agents and new approaches continue to be developed as an increasing number of patients in practice have exhausted all treatment options
The rationale of this study is based upon the existing literature which indicates that many of the manifestations and subsequent clinical deterioration of HIV-infected individuals are related to the immune dysfunction seen in HIV disease many of which are caused by the overproduction of proinflammatory cytokines most notable of which is the excessive production of TNF-α It is further postulated that removal of this TNF-α by a commercially available TNF-α-binding medication ENBREL etanercept may provide therapeutic benefit for HIV-infected patients who have failed to respond to standard antiretroviral therapy
II Goal and Objectives
The purpose of the project is to assess the safety profile and efficacy of a soluble p75 tumor necrosis factor TNF receptor Fc fusion protein Enbrel Amgen etanercept Thousand Oaks CA ie anti TNF-α on the response rate of salvage patients who are in virologic failure and who have failed to respond to standard antiretroviral therapy
The protocol will evaluate
1 Changes in CD4 T-cell enumeration viral load and soluble immune activation markers in HIV-infected patients from baseline to week 24 following treatment with anti-TNF-α
2 Safety and tolerability of anti-TNF-α with respect to treatment-limiting symptoms and laboratory adverse events through week 24
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