Ignite Creation Date:
2024-05-05 @ 11:12 PM
Last Modification Date:
2024-10-26 @ 10:30 AM
Study NCT ID:
NCT01276236
Status:
COMPLETED
Last Update Posted:
2021-03-05
First Post:
2010-12-20
Brief Title:
Effects of Maraviroc MVC on HIV-related Kaposis Sarcoma KS
Sponsor:
University of California San Francisco
Organization:
University of California San Francisco
Study Overview
Official Title:
Effects of Maraviroc MVC on HIV-related Kaposis Sarcoma KS
Status:
COMPLETED
Status Verified Date:
2021-03
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:
The purpose of this pilot study is to determine whether Maraviroc is effective in the treatment of Kaposis Sarcoma KS when it does not remit with standard antiretroviral drug therapy
Detailed Description:
Although the advent of antiretroviral therapy ART may have greatly decreased the incidence of Kaposis Sarcoma KS in resource rich settings KS continues to be the most prevalent AIDS-defining malignancy in the world and carries with it significant morbidity and mortality Indeed in a recent epidemiological study examining cancers in Kampala Uganda KS was found to be second only to prostate cancer in terms of incidence rates
There is growing evidence that C-C chemokine receptor 5 CCR5 may be involved in the pathogenesis of KS Kaposis Sarcoma-associated Herpes Virus KSHV an agent found as necessary for KS pathogenesis encodes viral macrophage inflammatory proteins or vMIP vMIP-I and vMIP-II have been found to be ligands for chemokine receptors and in particular the CCR5 receptor 5 6 suggesting a potential role in the inflammatory process needed for KS pathogenesis Further vMIP-I induces Ca2 mobilization in monocytes expressing CCR5 suggesting an agonistic relationship between vMIP-I and the CCR5 receptor In addition vMIP has been found to be proangiogenic when expressed in endothelial cells a key feature of KS tumor survival As well CCR5 has been found to be significantly increased in T cells populations of KS patients from a preliminary study and in 2 double-blind placebo-controlled phase 3 studies in which a total of 1049 patients received the randomly assigned drug MVC there was a trend revealing a lower incidence of KS in MVC arms vs placebo 036 vs 143 This agonistic binding relationship between protein vMIP and CCR5 the proangiogenic activity associated with vMIP the increased expression of CCR5 in KS and trend towards lower incidence of KS when patients are taking MVC suggest CCR5 may play an important role in KS pathogenesis This involvement of CCR5 in KS pathogenesis implies that MVC may function as a potential therapeutic for KS To date there have been no studies examining the effect of MVC on KS
There is a need for therapeutic development for KS Standard of care for KS involves initiation or optimization of antiretroviral therapy A significant proportion of KS cases do not respond to ART alone with non-response rates ranging from 25-55 with response times averaging 9 or more months depending on which patient series is identified In severe or in cases of KS unresponsive to ART standard of care involves systemic chemotherapy with liposomal doxorubicin which is not without adverse reactions Adverse reactions to liposomal doxorubicin include cardiac toxicity nausea vomiting diarrhea abdominal pain fatigue and patients may require pre-regime tests of varying costs along with resources and time needed for intravenous infusion Nonresponse rates for liposomal doxorubicin hover around 20 Focal cases may be more amenable to radiation therapy or intralesional velban However radiation and intralesional therapies are limited to focal sites require monitored visits and specialized care can be given only in limited amounts and carry various adverse effects With these nonresponse rates potential adverse reactions and resources and time needed for therapeutic delivery there are clear benefits proffered by an effective oral therapy requiring minimal monitoring as is the case with MVC
Maraviroc MVC is a member of a new class of antiretroviral compounds known as small molecule CCR5 antagonists that block R5 HIV entry into cluster of differentiation 4 CD4 cells Maraviroc has demonstrated selective and reversible binding to CCR5 as well as potent antiviral activity in vitro against a wide range of laboratory adapted strains of R5 HIV from Clades A B C D E F G J and O Maraviroc also retains in vitro antiviral activity against clinical isolates resistant to the existing drug classes but has no activity against viruses that enter CD4 cells using CXCR4 In vitro studies with approved antiretroviral medications indicate that there is no evidence of antagonism with any members of the other four classes of antiretroviral medications nucleosidenucleotide reverse transcriptase inhibitors NRTIs non- nucleoside reverse transcriptase inhibitors NNRTIs protease inhibitors PIs or fusion inhibitors
Although there is growing evidence that CCR5 a potential therapeutic target is involved in KS pathogenesis to date there are no studies examining the effects of a CCR5 inhibitor such as Maraviroc MVC on KS As such the aim of this study is to examine the effect of Maraviroc a CCR5 inhibitor on KS
There is growing evidence that C-C chemokine receptor 5 CCR5 may be involved in the pathogenesis of KS Kaposis Sarcoma-associated Herpes Virus KSHV an agent found as necessary for KS pathogenesis encodes viral macrophage inflammatory proteins or vMIP vMIP-I and vMIP-II have been found to be ligands for chemokine receptors and in particular the CCR5 receptor 5 6 suggesting a potential role in the inflammatory process needed for KS pathogenesis Further vMIP-I induces Ca2 mobilization in monocytes expressing CCR5 suggesting an agonistic relationship between vMIP-I and the CCR5 receptor In addition vMIP has been found to be proangiogenic when expressed in endothelial cells a key feature of KS tumor survival As well CCR5 has been found to be significantly increased in T cells populations of KS patients from a preliminary study and in 2 double-blind placebo-controlled phase 3 studies in which a total of 1049 patients received the randomly assigned drug MVC there was a trend revealing a lower incidence of KS in MVC arms vs placebo 036 vs 143 This agonistic binding relationship between protein vMIP and CCR5 the proangiogenic activity associated with vMIP the increased expression of CCR5 in KS and trend towards lower incidence of KS when patients are taking MVC suggest CCR5 may play an important role in KS pathogenesis This involvement of CCR5 in KS pathogenesis implies that MVC may function as a potential therapeutic for KS To date there have been no studies examining the effect of MVC on KS
There is a need for therapeutic development for KS Standard of care for KS involves initiation or optimization of antiretroviral therapy A significant proportion of KS cases do not respond to ART alone with non-response rates ranging from 25-55 with response times averaging 9 or more months depending on which patient series is identified In severe or in cases of KS unresponsive to ART standard of care involves systemic chemotherapy with liposomal doxorubicin which is not without adverse reactions Adverse reactions to liposomal doxorubicin include cardiac toxicity nausea vomiting diarrhea abdominal pain fatigue and patients may require pre-regime tests of varying costs along with resources and time needed for intravenous infusion Nonresponse rates for liposomal doxorubicin hover around 20 Focal cases may be more amenable to radiation therapy or intralesional velban However radiation and intralesional therapies are limited to focal sites require monitored visits and specialized care can be given only in limited amounts and carry various adverse effects With these nonresponse rates potential adverse reactions and resources and time needed for therapeutic delivery there are clear benefits proffered by an effective oral therapy requiring minimal monitoring as is the case with MVC
Maraviroc MVC is a member of a new class of antiretroviral compounds known as small molecule CCR5 antagonists that block R5 HIV entry into cluster of differentiation 4 CD4 cells Maraviroc has demonstrated selective and reversible binding to CCR5 as well as potent antiviral activity in vitro against a wide range of laboratory adapted strains of R5 HIV from Clades A B C D E F G J and O Maraviroc also retains in vitro antiviral activity against clinical isolates resistant to the existing drug classes but has no activity against viruses that enter CD4 cells using CXCR4 In vitro studies with approved antiretroviral medications indicate that there is no evidence of antagonism with any members of the other four classes of antiretroviral medications nucleosidenucleotide reverse transcriptase inhibitors NRTIs non- nucleoside reverse transcriptase inhibitors NNRTIs protease inhibitors PIs or fusion inhibitors
Although there is growing evidence that CCR5 a potential therapeutic target is involved in KS pathogenesis to date there are no studies examining the effects of a CCR5 inhibitor such as Maraviroc MVC on KS As such the aim of this study is to examine the effect of Maraviroc a CCR5 inhibitor on KS
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2860798 | OTHER | FDA IND Exemption Reference ID | None |