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

NCT04720742 | Withdrawn Phase 2 DMC

• 1 other identifier: ITATI
• Study Type: interventional
• Target: N/A
• Locations: 3 countries
• Sites: 4

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.

Conditions

HIV Infection

Keywords

analytical treatment interruption; broadly neutralizing antibodies; immune therapy; allogeneic stem cell transplantation

Outcome Measures

Primary Outcomes (3)

• Time to reappearance of HIV-1 viremia

  Time to reappearance of HIV-1 viremia (plasma HIV-1 RNA level \> 50 copies/ml in 2 consecutive measurements) after ART interruption.

  From Baseline to 18 months

• Time to reappearance of HIV-1 replication competent reservoir

  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.

  From Baseline to 18 months

• Time to reappearance of HIV-1 total reservoir

  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.

  From Baseline to 18 months

Secondary Outcomes (2)

• Rate and severity of adverse events (AE) and serious adverse events (SAE)

  From Baseline to 18 months

• Serum levels of 3BNC117 and 10-1074

  From Baseline to 18 months

Other Outcomes (15)

• Levels of residual HIV-1 RNA and viral proteins in plasma

  Visits from Baseline to 8 months

• Levels of cellular HIV-1 RNA

  Visits from Baseline to 8 months

• Quality of the autologous antibodies.

  Visits from Baseline to 8 months

Study Arms (1)

Experimental group

EXPERIMENTAL

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

Interventions

Analytical Treatment Interruption + bNAbs infusion DRUG

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

Experimental group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• IrsiCaixa: lead

Study Sites (4)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano

Milan, Lombardy, 20122, Italy

Location

University Medical Center Utrecht

Utrecht, 3584, Netherlands

Location

Complejo Hospitalario Universitario de Granada

Granada, Andalusia, 18014, Spain

Location

Hospital Gregorio Marañón

Madrid, 28009, Spain

Location

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: \- 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.

Study Record Dates

• First Submitted: December 12, 2019
• First Posted: January 22, 2021
• Study Start: February 28, 2021
• Primary Completion: March 28, 2022
• Study Completion: March 28, 2022
• Last Updated: August 3, 2022

Record last verified: 2022-08

Locations

ES (2); IT (1); NL (1)