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10-1074-Ls

This article discusses clinical trials investigating 10-1074-LS, a long-acting broadly neutralizing antibody (bNAb) for HIV treatment. The trials evaluate whether 10-1074-LS, used in combination with another antibody called 3BNC117-LS, can help maintain viral control after stopping antiretroviral therapy (ART). Studies focus on people living with HIV who have achieved viral suppression.

Table of Contents

Overview of 10-1074-LS Clinical Research

10-1074-LS is a long-acting broadly neutralizing antibody (bNAb) being investigated in clinical trials for HIV treatment[1][2]. Unlike traditional antiretroviral therapy that uses small molecule drugs, broadly neutralizing antibodies are proteins that can recognize and neutralize multiple strains of HIV by targeting conserved regions of the virus that do not easily mutate[1][2].

Current clinical research focuses on using 10-1074-LS in combination with another broadly neutralizing antibody called 3BNC117-LS as a dual therapy approach[1][2]. The primary goal of these studies is to determine whether this antibody combination can maintain viral suppression after participants stop their regular antiretroviral therapy[1][2].

Two Phase 2 clinical trials are currently authorized to investigate 10-1074-LS[1][2]. Phase 2 trials represent an important stage in drug development where researchers evaluate whether a treatment works effectively in larger groups of participants and continue to monitor safety[1][2]. These studies are interventional, meaning participants receive active treatment or placebo as part of the research design[1][2].

The RIO Trial: Evaluating Viral Control After Treatment Interruption

The RIO Trial (NCT04319367) is a Phase 2 clinical study enrolling 87 participants with HIV[1]. This trial uses a placebo-controlled design, which means some participants receive the active antibody treatment while others receive an inactive placebo infusion[1]. This design helps researchers determine whether the treatment truly provides benefit beyond what might occur naturally.

The primary objective of the RIO Trial is to determine the efficacy of dual bNAb infusion using 10-1074-LS and 3BNC117-LS at sustaining virological control compared with placebo infusion[1]. Virological control refers to keeping HIV levels in the blood low or undetectable without standard antiretroviral medications.

The trial involves an analytical treatment interruption (ATI), which is a carefully monitored pause in regular antiretroviral therapy[1]. During this interruption, researchers closely track participants’ viral levels to see if the antibody treatment can prevent the virus from rebounding.

Primary Outcome Measurement

The main outcome the RIO Trial measures is the time to viral rebound within 20 weeks after the initial analytical treatment interruption[1]. Viral rebound occurs when HIV levels in the blood increase after being suppressed[1]. By measuring how long participants can maintain viral control without standard therapy, researchers can evaluate whether the antibody combination provides meaningful benefit.

Treatment Regimen

In the RIO Trial, participants receive the following interventions[1]:

  • 3BNC117-LS: Administered as an intravenous infusion at a concentration of 150 mg/ml[1]
  • 10-1074-LS: Administered as an intravenous infusion at a concentration of 150 mg/ml[1]
  • Sodium Chloride 0.9%: Used as the placebo infusion for the control group at 150 mg/ml[1]

Trial in Primary HIV-1 Infection

A second Phase 2 trial (NCT05300035) focuses specifically on people with primary HIV-1 infection, which refers to the earliest stage of HIV infection occurring within the first few weeks to months after the virus enters the body[2]. This trial enrolls 69 participants and uses a randomized, placebo-controlled design[2].

The study’s main objective is to evaluate whether administering dual long-acting HIV-specific broadly neutralizing antibodies (3BNC117-LS and 10-1074-LS) in combination with antiretroviral therapy during primary infection can promote a period of HIV-1 remission when ART is interrupted 52 or 76 weeks later[2]. This approach tests whether treating HIV very early with antibodies might help the immune system better control the virus long-term.

Study Design and Timeline

Participants in this trial receive either[2]:

  • Antiretroviral therapy plus dual broadly neutralizing antibodies (10-1074-LS and 3BNC117-LS)
  • Antiretroviral therapy plus placebo (sodium chloride infusion)

After 52 or 76 weeks of treatment, participants undergo an analytical treatment interruption to assess whether they can maintain viral control without ongoing antiretroviral therapy[2]. The extended treatment period before interruption allows the antibodies and immune system more time to potentially establish better control over the virus.

Primary Outcome: Post-Treatment Controllers

The primary outcome measured in this trial is the proportion of participants with plasma HIV-1 RNA below 400 copies per milliliter (cp/mL) at 24 weeks following analytical treatment interruption, in the confirmed absence of antiretroviral therapy[2]. Participants who achieve this milestone are considered post-treatment controllers (PTCs)[2].

Post-treatment controllers represent individuals who can maintain low viral levels for extended periods without medication, essentially achieving a functional cure or remission of HIV[2]. This outcome is particularly significant because it suggests the treatment approach might help the body naturally control HIV without lifelong daily medication.

Dosing in Primary Infection Trial

The dosing regimen in this trial differs from the RIO Trial[2]:

  • 10-1074-LS: Administered at 10 mg per kilogram of body weight as an intravenous infusion[2]
  • 3BNC117-LS: Administered at 30 mg per kilogram of body weight as an intravenous infusion[2]
  • Sodium Chloride: Used as placebo, administered as 100 ml intravenous infusion[2]

The weight-based dosing ensures that each participant receives an appropriate amount of medication based on their individual body size.

How 10-1074-LS Works in Clinical Studies

While these trials focus on clinical outcomes rather than detailed mechanisms, understanding the basic approach helps explain why researchers are studying 10-1074-LS. The antibody is designed to target specific sites on the HIV virus that remain relatively constant across different viral strains[1][2].

The “LS” modification in 10-1074-LS refers to changes made to extend the antibody’s duration of action in the body, making it long-acting[1][2]. This extended half-life means the antibody remains active in the bloodstream for longer periods, potentially reducing the frequency of infusions needed.

Dual Antibody Approach

Both trials use 10-1074-LS in combination with 3BNC117-LS rather than as a single therapy[1][2]. This dual approach serves multiple purposes:

  • Broader coverage: Each antibody targets different sites on HIV, potentially neutralizing more viral variants
  • Reduced resistance: Using two antibodies makes it harder for the virus to develop mutations that escape both treatments simultaneously
  • Enhanced efficacy: The combined effect of two antibodies may be stronger than either alone

Administration and Dosing in Clinical Trials

In all current clinical trials, 10-1074-LS is administered via intravenous infusion, meaning the medication is delivered directly into a vein[1][2]. This route of administration ensures the antibody enters the bloodstream immediately and completely, which is important for achieving therapeutic levels.

Concentration and Dosing Variations

The trials use different dosing approaches[1][2]:

  • The RIO Trial uses a fixed concentration of 150 mg/ml for both antibodies[1]
  • The primary infection trial uses weight-based dosing, with 10-1074-LS at 10 mg/kg and 3BNC117-LS at 30 mg/kg[2]

These different approaches reflect varying study designs and research questions. Weight-based dosing accounts for individual body size differences, while fixed concentration dosing may simplify administration in certain study contexts.

Infusion Process

Intravenous infusions typically take place in clinical settings where healthcare professionals can monitor participants during and after administration. The infusion process allows for careful observation of any immediate reactions and ensures proper delivery of the medication.

Measured Outcomes and Endpoints

Clinical trials investigating 10-1074-LS focus on specific, measurable outcomes that help researchers determine whether the treatment approach is effective.

Viral Rebound Timing

The RIO Trial’s primary endpoint focuses on time to viral rebound within a 20-week window after stopping antiretroviral therapy[1]. This measurement provides insight into how long the antibody combination can maintain viral suppression without standard medications. Longer times to rebound suggest greater treatment efficacy.

Post-Treatment Control Rates

The primary infection trial measures the proportion of participants who achieve post-treatment controller status, defined as maintaining plasma HIV-1 RNA below 400 cp/mL at 24 weeks after treatment interruption[2]. This binary outcome (achieved or not achieved) helps researchers understand what percentage of participants benefit from the intervention.

The 400 cp/mL threshold represents a clinically meaningful level of viral control. While not as low as the typical goal of undetectable virus (usually below 20-50 cp/mL), maintaining levels below 400 cp/mL without medication represents significant viral suppression and reduced disease progression risk.

Monitoring During Analytical Treatment Interruption

Both trials involve careful monitoring during analytical treatment interruption periods[1][2]. This monitoring typically includes:

  • Regular viral load testing: Measuring HIV RNA levels in blood samples to detect any increase in viral replication
  • CD4 count monitoring: Tracking immune cell levels to ensure participant safety
  • Clinical assessments: Evaluating overall health and any symptoms that might indicate viral rebound
  • Safety monitoring: Watching for any adverse effects from the antibody infusions or treatment interruption

If participants experience significant viral rebound or declining immune function during the interruption period, they can restart antiretroviral therapy to protect their health. This safety mechanism ensures that research participation does not compromise long-term health outcomes.

Comparison with Placebo

Both trials use placebo controls (sodium chloride infusions) to provide rigorous comparison groups[1][2]. By comparing outcomes between participants receiving the antibody combination and those receiving placebo, researchers can determine whether observed benefits result from the treatment itself rather than other factors like natural viral control variability or the effects of the analytical treatment interruption process.

Trial ID Trial Name Phase Condition Status Enrollment Primary Outcome
NCT04319367 RIO Trial Phase 2 HIV Authorised 87 Time to viral rebound within 20 weeks after initial ATI
NCT05300035 ART plus dual bNAbs in primary HIV-1 infection Phase 2 HIV (Primary Infection) Authorised 69 Proportion with HIV-1 RNA below 400 cp/mL at 24 weeks post-ATI

FAQ

  • What is being studied in clinical trials with 10-1074-LS? Clinical trials are investigating whether 10-1074-LS, combined with another antibody called 3BNC117-LS, can help people with HIV maintain viral control after stopping their regular antiretroviral therapy. The studies examine how long participants can remain without viral rebound and whether they can achieve post-treatment control of HIV.
  • Who can participate in these 10-1074-LS clinical trials? The trials enroll people living with HIV-1 infection. Some studies focus on individuals with primary (recent) HIV infection, while others include participants who have achieved viral suppression on antiretroviral therapy. Specific eligibility criteria vary by trial.
  • What phase are the 10-1074-LS clinical trials in? The current clinical trials investigating 10-1074-LS are Phase 2 studies. This phase evaluates the efficacy and safety of the treatment in larger groups of participants to determine if it works as intended.
  • How is 10-1074-LS administered in these trials? In clinical trials, 10-1074-LS is given as an intravenous infusion, meaning it is delivered directly into a vein. It is administered together with another antibody called 3BNC117-LS as a dual therapy approach.
  • What are the main outcomes being measured in these trials? The trials measure time to viral rebound after stopping antiretroviral therapy and the proportion of participants who maintain viral control below certain levels. Researchers track how many participants can control HIV without antiretroviral therapy for extended periods.

Ongoing Clinical Trials on 10-1074-Ls

  • Study on the Effectiveness of 10-1074-LS and Teropavimab in Controlling HIV in Patients with Early Stage HIV Infection

    Recruiting

    1 1
    Investigated drugs:
    Belgium Denmark Germany The Netherlands Spain Sweden

  • Study of teropavimab (3BNC117-LS) and 10-1074-LS antibodies combined with antiretroviral therapy in patients with primary HIV-1 infection to evaluate viral control

    Recruiting

    1 1
    Investigated drugs:
    France

Glossary

  • Broadly Neutralizing Antibodies (bNAbs): Special proteins produced by the immune system that can recognize and neutralize many different strains of HIV. They target parts of the virus that do not change easily, making them effective against various HIV types.
  • Antiretroviral Therapy (ART): A combination of medications used to treat HIV infection. These drugs work together to suppress the virus and prevent it from multiplying in the body.
  • Analytical Treatment Interruption (ATI): A planned, carefully monitored pause in antiretroviral therapy during a clinical trial. This allows researchers to study whether experimental treatments can maintain viral control without standard HIV medications.
  • Viral Rebound: When HIV levels in the blood increase after being suppressed. This typically occurs when antiretroviral therapy is stopped or when the virus develops resistance to treatment.
  • Post-Treatment Controller (PTC): A person who can maintain low or undetectable HIV levels for an extended period after stopping antiretroviral therapy. This represents a form of HIV remission without ongoing medication.
  • Primary HIV Infection: The earliest stage of HIV infection, typically occurring within the first few weeks to months after the virus enters the body. Also called acute HIV infection.
  • Viral Suppression: When HIV levels in the blood are reduced to very low or undetectable levels, usually through effective antiretroviral therapy. This prevents disease progression and transmission.
  • Plasma HIV-1 RNA: A measurement of the amount of HIV genetic material in the blood. This test, also called viral load, indicates how actively the virus is replicating.
  • Intravenous Infusion: A method of delivering medication directly into a vein through a needle or catheter. This allows the drug to enter the bloodstream immediately.
  • Placebo-Controlled Trial: A study design where some participants receive the experimental treatment while others receive an inactive substance (placebo). This helps researchers determine if the treatment truly works.

References