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Immune Therapy and Analytical Treatment Interruption in HIV+ Participants Who Received an Allogeneic Stem Cell Transplantation (ITATI)

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ClinicalTrials.gov Identifier: NCT04720742
Recruitment Status : Suspended (Due to the COVID-19 pandemic the financial sponsor of the trial suspended the study funding due to funding limitations and based on various considerations, including the uncertainties of conducting the study in the volatile scenario of this pandemic.)
First Posted : January 22, 2021
Last Update Posted : January 22, 2021
Sponsor:
Information provided by (Responsible Party):
IrsiCaixa

Brief Summary:

The availability of antiretroviral therapy (cART) for HIV-1 infection has led to a reduction in morbidity in patients with chronic HIV infection. However, cART does not eliminate HIV-1 that persists as a latent infection in cellular reservoirs. Usually, HIV viremia rapidly rebounds if antiretroviral therapy is interrupted. Consequently, HIV infected individuals must commit to expensive, life-long therapies and must tackle problems associated with chronic infection and uninterrupted cART, including continuous clinical and laboratory monitoring, drug toxicities, and chronic immune activation/inflammation.

Currently, there is an emerging interest in developing safe and affordable curative strategies that would eliminate the need for lifelong therapy. However, to date only allogeneic hematopoietic stem cell transplantation (allo-HSCT) has shown results in decreasing the HIV-1 reservoirs.

The IciStem Consortium (www.icistem.org) has assembled the largest and most exhaustive observational cohort for the study of HIV reservoir dynamics in allo-HSCT HIV+ individuals with severe hematological malignancies worldwide. Within the cohort, only individuals transplanted with a donor with thw CCR5A32 mutation have shown signs of HIV remission. On the other side broadly neutralizing antibodies (bNAbs) have shown the potential to control HIV infection. This study intends to evaluate if the allo-HSCT combined with the additional application of bNAbs is effective to control HIV replication.


Condition or disease Intervention/treatment Phase
HIV Infection Drug: Analytical Treatment Interruption + bNAbs infusion Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: - Experimental group: the intervention will consist of an Analytical Treatment Interruption (ATI) of up to 18 months of duration, and during the first 8 months, a temporary immune intervention including the combination of the broadly neutralizing antibodies (bNAbs) 3BNC117 and 10-1074, which will be infused once per month.
Masking: None (Open Label)
Primary Purpose: Health Services Research
Official Title: Immune Therapy and Analytical Treatment Interruption in HIV+ Participants Who Received an Allogeneic Stem Cell Transplantation (ITATI)
Estimated Study Start Date : January 2021
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Experimental group
The participant will perform an Analytical Treatment Interruption (ATI) of up to 18 months of duration, and during the first 8 months, a temporary immune intervention including the combination of the broadly neutralizing antibodies (bNAbs) 3BNC117 and 10-1074, which will be infused once per month.
Drug: Analytical Treatment Interruption + bNAbs infusion
The participant will perform an Analytical Treatment Interruption (ATI) of up to 18 months of duration. During the first 8 months, the participants will be infused once per month with a combination of the broadly neutralizing antibodies (bNAbs) 3BNC117 and 10-1074




Primary Outcome Measures :
  1. Time to reappearance of HIV-1 viremia [ Time Frame: From Baseline to 18 months ]
    Time to reappearance of HIV-1 viremia (plasma HIV-1 RNA level > 50 copies/ml in 2 consecutive measurements) after ART interruption.

  2. Time to reappearance of HIV-1 replication competent reservoir [ Time Frame: From Baseline to 18 months ]
    Time to reappearance of HIV-1 replication competent reservoir (determined by the number of infectious units per 106 CD4+ T cells (IUPM) using a viral outgrowth assay) after ART interruption.

  3. Time to reappearance of HIV-1 total reservoir [ Time Frame: From Baseline to 18 months ]
    Time to reappearance of HIV-1 total reservoir (determined by the number HIV-DNA copies per 106 CD4+ T cells using ddPCR) after ART interruption.


Secondary Outcome Measures :
  1. Rate and severity of adverse events (AE) and serious adverse events (SAE) [ Time Frame: From Baseline to 18 months ]
    Safety evaluation, as measured by rate and severity of adverse events (AE) and serious adverse events (SAE).

  2. Serum levels of 3BNC117 and 10-1074 [ Time Frame: From Baseline to 18 months ]
    Serum levels of 3BNC117 and 10-1074 throughout the study


Other Outcome Measures:
  1. Levels of residual HIV-1 RNA and viral proteins in plasma [ Time Frame: Visits from Baseline to 8 months ]
    Levels of residual HIV-1 RNA and viral proteins in plasma before, during and after infusions of 3BNC117 and 10-1074.

  2. Levels of cellular HIV-1 RNA [ Time Frame: Visits from Baseline to 8 months ]
    Levels of cellular HIV-1 RNA before, during and after infusions of 3BNC117 and 10-1074

  3. Quality of the autologous antibodies. [ Time Frame: Visits from Baseline to 8 months ]
    HIV-1 specific humoral cell immune responses before, during and following 3BNC117 and 10-1074 infusions, including quantity and quality of the autologous antibodies.

  4. Quantity of the autologous antibodies. [ Time Frame: Visits from Baseline to 8 months ]
    HIV-1 specific humoral cell immune responses before, during and following 3BNC117 and 10-1074 infusions, including quantity and quality of the autologous antibodies.

  5. Immunophenotype and functional characteristics of NK, B and T cells from peripheral blood [ Time Frame: Visits from Baseline to 8 months ]
    Immunophenotype and functional characteristics of NK, B and T cells from peripheral blood before, during and following the 3BNC117 and 10-1074 infusions.

  6. Measurement of Immune activation and proliferation markers [ Time Frame: Visits from Baseline to 8 months ]
    Measurement of immune activation and proliferation markers, before, during and following 3BNC117 and 10-1074 infusions.

  7. Measurement of plasma biomarkers [ Time Frame: At viral rebound ]
    Measurement of plasma biomarkers and relate them to HIV viral rebound.

  8. Genome amplification (SGA), phenotypic characterization and full genome analysis of rebounded viruses [ Time Frame: From Baseline and 12 weeks after viral re-suppression ]
    Single genome amplification (SGA), phenotypic characterization and full genome analysis (integration sites and tropism) of rebounded viruses after ART interruption, and after at least 12 weeks after ART re-suppression of viral replication

  9. Immunophenotype and functional characteristics of viral specific T cells [ Time Frame: At viral rebound ]
    Immunophenotype and functional characteristics of viral specific T cells in the viral rebound.

  10. Measurement of HIV-1 total reservoir [ Time Frame: At 18 months without viral rebound ]
    Measurement of HIV-1 total reservoir (determined by the number of HIV-DNA or HIV-RNA copies using ddPCR) in ileum, bone marrow, lymph node and CSF biopsies after 18 months of treatment interruption without viral rebound.

  11. Evaluation of the HIV latent reservoirs in blood [ Time Frame: At 18 months without viral rebound ]
    Evaluation of the HIV latent reservoirs in blood by infusion of the participant's CD4+ T cells in a mice model after 18 months of treatment interruption without viral rebound.

  12. Measurement of ultra-chimerism in blood and tissue populations [ Time Frame: Visits from Baseline to 8 months ]
    Measurement of ultra-chimerism in blood and tissue populations before, during and after the 3BNC117 and 10-1074 infusions

  13. Analysis of metabolic products of glycolysis in plasma [ Time Frame: Visits from Baseline to 8 months ]
    Analysis of metabolic products of glycolysis in plasma before, during and after the 3BNC117 and 10-1074 infusions.

  14. Change in the scores assessing psychological predisposition to Analytical Treatment Interruption (ATI) and emotional status [ Time Frame: At Screening, Baseline, 1 month, 8 months, 9 months, 12 months, 18 months and 3 months after viral suppression ]
    Evaluation of significant change in the scores assessing psychological predisposition to Analytical Treatment Interruption (ATI) and emotional status.

  15. Quantification of the satisfaction level [ Time Frame: At 8 months, 18 months and 3 months after viral suppression ]
    Quantification of the satisfaction levels of the participation in the study.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • More than 2 years post-HSCT
  • Being off immunosuppression for at least one year (related to allo-HSCT)
  • Undetectable levels of HIV replication competent reservoirs in blood (< 0,1 IUPM).
  • CD4 count levels higher than 200 cel/mm3.
  • Aged at least 18 years and not older than 65 at the day of screening
  • Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
  • In the opinion of the principal investigator or designee, the participant has understood the information provided and capable of giving written informed consent.
  • If heterosexually active female; using an effective method of contraception (hormonal contraception, intra-uterine device (IUD), or anatomical sterility in self or partner1) from 14 days prior to the first bNAbs administration until at least 6 months after the last bNAbs administration; all female volunteers must be willing to undergo urine pregnancy tests at time points specified.
  • If heterosexually active male; willing to use an effective method of contraception (anatomical sterility in self) or agree on the use of an effective method of contraception by his partner(hormonal contraception, intra-uterine device (IUD), or anatomical sterility1 from the day of the first bNAbs administration until 6 months after the last bNAbs administration.
  • Willing to accept blood draws at time points specified.
  • Not sharing injection drug equipment, such as needles.

    1. Condom use nor diaphragm are considered as an additional method of contraception only and cannot be the only method of contraception used as not been considered an effective method by the Clinical Trial Facilitation Group (CTFG) guidelines.

Exclusion Criteria:

  • Pregnancy or lactating
  • Participation in another clinical trial within 12 weeks of study entry (at screening period).
  • History or clinical manifestations of any physical or psychiatric disorder which could impair the subject's ability to complete the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04720742


Locations
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Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
Milan, Lombardy, Italy, 20122
Netherlands
University Medical Center Utrecht
Utrecht, Netherlands, 3584
Spain
Complejo Hospitalario Universitario de Granada
Granada, Andalucia, Spain, 18014
Hospital Gregorio Marañón
Madrid, Spain, 28009
Sponsors and Collaborators
IrsiCaixa
Investigators
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Principal Investigator: Jose L Diez Gregorio Marañón Hospital
Principal Investigator: Manuel Jurado Complejo Hospitalario Universitario de Granada
Principal Investigator: Alessandra Bandera Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico de Milano
Principal Investigator: Annemarie Wensing UMC Utrecht
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Responsible Party: IrsiCaixa
ClinicalTrials.gov Identifier: NCT04720742    
Other Study ID Numbers: ITATI
First Posted: January 22, 2021    Key Record Dates
Last Update Posted: January 22, 2021
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by IrsiCaixa:
analytical treatment interruption
broadly neutralizing antibodies
immune therapy
allogeneic stem cell transplantation
Additional relevant MeSH terms:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases