NCT03588715

Peg-Interferon Alpha 2b Combined With Two Intravenous Broadly HIV-1 Neutralizing Antibodies 3BNC117 and 10-1074 (BEAT-2)

Pilot Study on Innate Activation and Viral Control in HIV-Infected Adults Undergoing an Analytical Treatment Interruption After Administration of Pegylated Interferon Alpha 2b With Broadly HIV-1 Neutralizing Antibodies (3BNC117, 10-1074)

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: Luis Montaner · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will evaluate the safety, tolerability and innate immune mechanisms activation following administration of the combination of Pegylated Interferon alpha 2b (peg-IFN-α2b) with two broadly neutralizing antibodies (3BNC117 and 10-1074) in the setting of well-controlled HIV infection with antiretroviral treatment and a monitored analytical treatment interruption. The current proposal builds on previous experience using interferon alpha, 3BNC117 and 10-1074 alone in separate clinical trials that included a closely monitored analytical treatment interruption. The hypothesis is that the joint administration of peg-IFN-α2b with 3BNC117 and 10-1074 will be more effective than either intervention separately in suppressing HIV viremia during 8 weeks of analytical treatment interruption (Step 4) and reducing integrated HIV DNA in blood and tissue when measured during an analytical treatment interruption in patients with well-controlled HIV infection.

Detailed description

The proposed study will evaluate the safety, tolerability and innate immune mechanisms activation following administration of the combination of Pegylated Interferon alpha 2b (peg-IFN-α2b) with two broadly neutralizing antibodies (3BNC117 and 10-1074) in the setting of well controlled HIV infection with antiretroviral treatment and a monitored analytical treatment interruption. This proposal builds on previous experience using interferon alpha, 3BNC117 and 10-1074 alone in separate clinical trials that included a closely monitored analytical treatment interruption. The hypothesis is that the joint administration of peg-IFN-α2b with 3BNC117 and 10-1074 will be more effective than either intervention separately in suppressing HIV viremia during 8 weeks of analytical treatment interruption (Step 4) and reducing integrated HIV DNA in blood and tissue when measured during an analytical treatment interruption in participants with well-controlled HIV infection. A review of the conceptual framework for the strategy to be tested includes: * Why peg-IFN-α2? The therapeutic effects of peg-IFN-α2 yield two essential outcomes that are the fundamental objectives of HIV curative strategies: control viral replication in the absence of ART and reduce the levels of integrated HIV DNA in CD4+ T-cells. To date, peg-IFN-α is the only intervention that has been shown to maintain viral suppression to levels \<50 copies/mL in the absence of ART in chronic infection. Preliminary data supports that correlates of anti-HIV reductions are centered on activation of NK responses. * Why bNAbs + peg-IFN-α2b? The addition of bNAbs may act independently to control virus replication or decrease fitness thereby increasing the potential for a larger antiviral effect after IFN by enhance NK-mediated clearance via a reduced viral levels and the complementarity of bNAbs in enhancing mechanisms of antibody-mediated cytotoxicity against infected cells by binding to virus emerging from or viral proteins expressed on activated latent cells. * Why combined bNAbs? In vivo, multiple bNAbs targeting different epitopes provide better neutralization and antigen recognition than single bNAbs, which suggests that adoptive transfer of multiple bNAbs may lead to superior viral control. Although bNAbs may have neutralization effects that are of greater clinical impact than ADCC, it is possible that antigen targeting through multiple bNAbs may also enhance NK-mediated cytotoxicity more than a single bNAb. The administration of broadly neutralizing antibodies alone in the setting of an analytical treatment interruption delays the return of viremia in a fraction of the participants. * Why test an ATI of immunotherapy? To date, peg-IFN-α2 administered prior to an ATI or ART and subsequently maintained throughout the ATI period has maintained viral suppression. An effective curative strategy requires that all interventions be discontinued.

Conditions

• HIV
• HIV/AIDS
• HIV-1 Infection

Interventions

Type	Name	Description
DRUG	Pegylated Interferon alpha 2b (peg-IFN-α2b)	Pegylated Interferon alpha 2b (peg-IFN-α2b) will be administered weekly via subcutaneous route.
DRUG	3BNC117 + 10-1074	Broadly Neutralizing Antibodies - Sequential, separate IV infusions of 3NBC117 + 10-1074.

Timeline

• Start date: 2020-06-18
• Primary completion: 2021-12-31
• Completion: 2022-10-30
• First posted: 2018-07-17
• Last updated: 2021-06-25

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study