Ignite Creation Date:
2024-05-06 @ 11:14 AM
Last Modification Date:
2024-10-26 @ 12:42 PM
Study NCT ID:
NCT03468582
Status:
COMPLETED
Last Update Posted:
2020-01-29
First Post:
2018-02-12
Brief Title:
123I Radiolabeled 3BNC117
Sponsor:
University of Lausanne Hospitals
Organization:
University of Lausanne Hospitals
Study Overview
Official Title:
Pilot Study Using 123I Radiolabeled 3BNC117 SPECTCT to Image HIV Reservoir in Chronically Infected HIV Patients
Status:
COMPLETED
Status Verified Date:
2020-01
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 conventional way to control HIV infection is the usage of a drug cocktail capable of suppressing the viral replication cycle commonly known as antiretroviral therapy ART Despite effective ART it is not possible to eradicate HIV The virus hides in particular cells to form the latent HIV-reservoir1-9 Studies that emphasise on revealing hidden reservoirs would aid in designing novel therapeutic strategies for controlling HIV infection Molecular imaging by SPECTCT has the potential to reveal hidden reservoirs of HIV virus that are not eliminated by currently used drugs capable of suppressing and thereby controlling the viral replication cycle in HIV infected patients New approaches necessary to prevent and treat HIV-1 infection are gradually emerging A new generation of highly potent broadly neutralizing antibodies bNAbs may represent a promising approach to combating HIV-1 infection10 The broadly neutralizing antibody 3BNC117 antibody that can mimic human CD4 binding targeted against the HIV gp120 envelope protein has been tested in various clinical trials11-14 It has found to be safe and effective in reducing viraemia and to improve host humoral responses in HIV-1 infected individuals and to have effect on viral rebound in patients who are kept off antiretroviral treatment briefly for experimental purpose
Imaging of simian immunodeficiency virus SIV infection by PETCT has been successfully performed in nonhuman primates with a 64Cu-labeled SIV gp120-specific antibody called 7D315 This study aims to use a similar approach in human with the 3BNC117 antibody The 3BNC117 antibody has been successfully radiolabeled with iodine 123 The half-life of this radioisotope is appropriate for antibody imaging in nuclear medicine Radiolabeled 123I 3BNC117 was shown to keep a good immunoreactivity for gp120 By using state of the art SPECT scanner a semi-quantitative image will be obtained In addition the absence of any chelator and the well known use of iodine-123 in clinic make it suitable for human intervention
No HIV imaging in human has been achieved yet which is however fundamental to understand some key steps in the pathogenesis of HIV-induced immunodeficiency This research opens promising opportunities for drug and vaccine development Indeed identification of virus reservoirs in treated patients would facilitate the development of strategies for eradicating these reservoirs or for extending latency period
Imaging of simian immunodeficiency virus SIV infection by PETCT has been successfully performed in nonhuman primates with a 64Cu-labeled SIV gp120-specific antibody called 7D315 This study aims to use a similar approach in human with the 3BNC117 antibody The 3BNC117 antibody has been successfully radiolabeled with iodine 123 The half-life of this radioisotope is appropriate for antibody imaging in nuclear medicine Radiolabeled 123I 3BNC117 was shown to keep a good immunoreactivity for gp120 By using state of the art SPECT scanner a semi-quantitative image will be obtained In addition the absence of any chelator and the well known use of iodine-123 in clinic make it suitable for human intervention
No HIV imaging in human has been achieved yet which is however fundamental to understand some key steps in the pathogenesis of HIV-induced immunodeficiency This research opens promising opportunities for drug and vaccine development Indeed identification of virus reservoirs in treated patients would facilitate the development of strategies for eradicating these reservoirs or for extending latency period
Detailed Description:
The conventional way to control HIV infection is by use of a cocktail of drugs capable of suppressing the viral replication cycle commonly known as antiretroviral therapy ART Despite effective ART it is not possible to eradicate HIV The virus hides in particular cells to form the latent HIV-reservoir and antiviral agents have no effect on these latently infected HIV cells1-9 Studies by Chomont et al identified particular CD4 T cell subsets that serve as key cellular compartment for latent HIV-1 reservoir in blood6 A later study has identified memory CD4 T cells with stem-cell like properties as a minor latent HIV-1 reservoir7 A major part of this reservoir is in the lymphoid tissue which constitute the predominant site for lymphocytes One recent study has identified follicular T helper cells TFH of lymph nodes as major CD4 T cell compartments for HIV-1 replication production and infection8 Further characterisation of the different CD4 T cell population has identified a specific cell population expressing PD-1 as the major CD4 T cell compartment in blood and lymph nodes for production of replication competent and infectious HIV-19 Thus studies that emphasise on revealing hidden reservoirs would aid in designing novel therapeutic strategies for controlling HIV infection Molecular imaging by SPECTCT has the potential to reveal hidden reservoirs of HIV virus that are not eliminated by use of currently used drugs capable of suppressing and thereby controlling the viral replication cycle in HIV infected patients
As discussed above even though ART can suppress virus replication and can limit disease progression it fails to eradicate the virus and suppression requires lifelong therapy which may have side effects and poses a risk of the development of resistance New approaches necessary to prevent and treat HIV-1 infection in order to restrict the epidemic and to strengthen nascent efforts in finding a cure are gradually emerging A new generation of highly potent broadly neutralizing antibodies bNAbs may represent a promising approach to combating HIV-1 infection10 Many sites on the viral envelope can be recognized by bNAbs
The broadly neutralising antibody 3BNC117 directed against the HIV gp120 envelope protein can mimic human CD4 binding and can neutralize 195 out of 237 HIV-1 strains11 The first human phase I dose escalation study using 3BNC117 has shown to be safe and effective in transiently reducing viraemia in chronic HIV-1 infected individuals12 A subsequent study ClinicalTrialgov identifierNCT02018510 demonstrated improved host humoral immune response in infected individuals treated with 3BNC117 antibody as compared to untreated individuals13 Furthermore a phase IIa open labelled trial by the same group of researchers at Rockefeller University NY has been carried out to evaluate the capacity of this antibody to suppress viral rebound in infected individuals during a brief treatment interruption of anti-retroviral therapy14 Another such trial is currently ongoing ClinicalTrialgov identifier NCT02446847
Imaging of simian immunodeficiency virus SIV infection by PETCT has been successfully performed in nonhuman primates with a 64Cu-labeled SIV gp120-specific antibody called 7D315 This study aims to use a similar approach in human with the 3BNC117 antibody The 3BNC117 antibody has been successfully radiolabeled with iodine-123 The half-life of this radioisotope is appropriate for antibody imaging in nuclear medicine Radiolabeled 123I-3BNC117 was shown to keep a good immunoreactivity in vitro for gp120 By using state of the art SPECT scanner a semi-quantitative image will be obtained In addition the well known use of iodine-123 in clinic and the absence of chelator makes it suitable for human intervention
No HIV imaging in human has yet been achieved which is however fundamental to understand some key steps in the pathogenesis of the HIV-induced immunodeficiency This research opens promising opportunities for monitoring the size of the HIV reservoir and for drug and vaccine development Indeed identification of virus reservoirs in treated patients would facilitate the development of strategies for eradicating these reservoirs or for extending latency period
As discussed above even though ART can suppress virus replication and can limit disease progression it fails to eradicate the virus and suppression requires lifelong therapy which may have side effects and poses a risk of the development of resistance New approaches necessary to prevent and treat HIV-1 infection in order to restrict the epidemic and to strengthen nascent efforts in finding a cure are gradually emerging A new generation of highly potent broadly neutralizing antibodies bNAbs may represent a promising approach to combating HIV-1 infection10 Many sites on the viral envelope can be recognized by bNAbs
The broadly neutralising antibody 3BNC117 directed against the HIV gp120 envelope protein can mimic human CD4 binding and can neutralize 195 out of 237 HIV-1 strains11 The first human phase I dose escalation study using 3BNC117 has shown to be safe and effective in transiently reducing viraemia in chronic HIV-1 infected individuals12 A subsequent study ClinicalTrialgov identifierNCT02018510 demonstrated improved host humoral immune response in infected individuals treated with 3BNC117 antibody as compared to untreated individuals13 Furthermore a phase IIa open labelled trial by the same group of researchers at Rockefeller University NY has been carried out to evaluate the capacity of this antibody to suppress viral rebound in infected individuals during a brief treatment interruption of anti-retroviral therapy14 Another such trial is currently ongoing ClinicalTrialgov identifier NCT02446847
Imaging of simian immunodeficiency virus SIV infection by PETCT has been successfully performed in nonhuman primates with a 64Cu-labeled SIV gp120-specific antibody called 7D315 This study aims to use a similar approach in human with the 3BNC117 antibody The 3BNC117 antibody has been successfully radiolabeled with iodine-123 The half-life of this radioisotope is appropriate for antibody imaging in nuclear medicine Radiolabeled 123I-3BNC117 was shown to keep a good immunoreactivity in vitro for gp120 By using state of the art SPECT scanner a semi-quantitative image will be obtained In addition the well known use of iodine-123 in clinic and the absence of chelator makes it suitable for human intervention
No HIV imaging in human has yet been achieved which is however fundamental to understand some key steps in the pathogenesis of the HIV-induced immunodeficiency This research opens promising opportunities for monitoring the size of the HIV reservoir and for drug and vaccine development Indeed identification of virus reservoirs in treated patients would facilitate the development of strategies for eradicating these reservoirs or for extending latency period
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None