A Nonrandomized Phase 1 Clinical Trial to Evaluate the Safety and Tolerability of DV700P-RNA and DV701B1.1-RNA Immunization in Combination With Antiretroviral Analytical Treatment Interruption (ATI) in People Living With HIV for Elicitation of V3-glycan Antibodies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 42
- 试验地点
- 31
- 主要终点
- Number and description of medically attended adverse events (MAAEs)
研究概览
简要总结
This phase 1 study will evaluate the safety, tolerability, and immune responses of two experimental mRNA HIV vaccines in adults living with HIV who are in overall good health. The study will enroll about 42 participants at multiple study sites. Researchers will assess whether these vaccines can start or strengthen antibody responses against HIV. The study will also evaluate how a closely monitored planned pause in antiretroviral therapy affects these immune responses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able and willing to provide informed consent.
- •Age 18 to 60 years.
- •Documented HIV infection.
- •Lowest (nadir) CD4+ count between 250 and 450 cells/mm³.
- •On stable combination antiretroviral therapy (ART) for at least 48 weeks prior to screening.
- •Plasma HIV RNA <50 copies/mL for at least 48 weeks prior to enrollment, allowing limited transient increases.
- •CD4+ count >450 cells/mm³ and CD4+ percentage ≥15%.
- •Willing and able to comply with study visits and procedures.
- •Agrees not to participate in another investigational study during participation unless approved.
- •In general good health, with no clinically significant findings on physical exam or laboratory testing.
- •Hemoglobin ≥11.0 g/dL (women) or ≥13.0 g/dL (men).
- •Absolute neutrophil count ≥750/mm³.
- •Platelet count ≥100,000/mm³.
- •ALT <2.5 × upper limit of normal.
- •Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m².
- •Serum creatinine ≤1.1 × upper limit of normal.
- •Serum calcium >8.5 mg/dL.
- •Blood pressure within acceptable limits.
- •Agrees to use condoms during the specified period when ART is interrupted until HIV RNA is undetectable.
- •No evidence of active hepatitis C infection.
- •No evidence of active hepatitis B infection.
- •For individuals of pregnancy potential: negative pregnancy test prior to enrollment and agreement to use effective contraception during the required study period.
- •Agreement not to seek pregnancy during the required study period.
排除标准
- •Current use of ART that includes non-nucleoside reverse transcriptase inhibitors (NNRTIs).
- •Use of long-acting ART within 3 months prior to enrollment.
- •Known resistance to any component of the current ART regimen (excluding M184V/I mutation).
- •Resistance to one or more drugs in two or more ART classes (excluding M184V/I mutation).
- •Initiation of ART during acute HIV infection (within 1 year of HIV acquisition, if known).
- •History of advanced HIV-related illness (CDC Category C), except recurrent pneumonia, within 10 years prior to screening, or history of CD4 count <200 cells/mm³ within the past 10 years.
- •History of severe HIV-related conditions, including opportunistic infections, HIV-associated cancers, lymphoma, neurocognitive disease, or progressive multifocal leukoencephalopathy.
- •Active or recent non-HIV-related cancer requiring systemic treatment within 36 months or expected need for treatment within 12 months (excluding minor skin cancers).
- •Active hepatitis B or hepatitis C infection.
- •Significant liver disease, including cirrhosis or advanced fatty liver disease.
- •Untreated or incompletely treated active or latent tuberculosis.
- •Pregnancy or breastfeeding.
- •Body mass index (BMI) ≥40 kg/m², unless approved.
- •Diabetes mellitus, except well-controlled type 2 diabetes as allowed.
- •History of or current atherosclerotic cardiovascular disease, including heart attack, angina, stroke, or peripheral arterial disease.
- •Previous receipt of an investigational HIV vaccine (prior placebo recipients allowed).
- •Receipt of a non-HIV investigational vaccine within 1 year, unless approved or licensed.
- •Conditions causing impaired immune function or use of immunosuppressive medications within the specified timeframe.
- •Prior receipt of anti-HIV monoclonal antibody therapy.
- •Receipt of certain vaccines within restricted timeframes prior to enrollment (including live or mRNA vaccines within 4 weeks).
- •Receipt of other vaccines within 14 days prior to enrollment.
- •History of myocarditis or pericarditis.
- •Recent initiation of allergy immunotherapy within 1 year (unless stable or approved).
- •Recent use of investigational agents within restricted timeframes prior to enrollment.
- •History of severe allergic reaction to mRNA vaccines or polyethylene glycol-containing products.
- •History of angioedema.
- •Idiopathic urticaria within the past year.
- •Chronic urticaria or urticaria within the past year.
- •History of urticaria associated with vaccination.
- •Bleeding disorders or use of systemic anticoagulants.
- •Conditions associated with increased risk of clotting or bleeding.
- •History of seizures within the past 3 years or use of anti-seizure medications within that period.
- •Absence of spleen or impaired splenic function.
- •Active duty or reserve military personnel (U.S.).
- •Any clinically significant medical, psychiatric, or substance use condition that may affect safety or study participation.
- •Uncontrolled or severe asthma.
- •History of immune-mediated medical conditions, except limited stable or resolved conditions as allowed.
- •Allergy to local anesthetics (e.g., lidocaine).
- •Difficulty with venous access that would interfere with study procedures.
研究组 & 干预措施
Group 2
Participants will receive:
- Week 0: DV700P-RNA
- Week 8: DV701B1.1-RNA
干预措施: DV700P-RNA 100 mcg (Biological)
Group 2
Participants will receive:
- Week 0: DV700P-RNA
- Week 8: DV701B1.1-RNA
干预措施: DV701B1.1-RNA 100 mcg (Biological)
Group 1
Participants will receive:
- Week 0: DV700P-RNA
- Week 8: DV700P-RNA
- Week 16: DV701B1.1-RNA
干预措施: DV700P-RNA 100 mcg (Biological)
Group 1
Participants will receive:
- Week 0: DV700P-RNA
- Week 8: DV700P-RNA
- Week 16: DV701B1.1-RNA
干预措施: DV701B1.1-RNA 100 mcg (Biological)
结局指标
主要结局
Number and description of medically attended adverse events (MAAEs)
时间窗: Through study completion, expected to be up to 88 weeks
Number and description of adverse events of special interest (AESIs)
时间窗: Through study completion, expected to be up to 88 weeks
Number and description of adverse events leading to study product discontinuation or participant withdrawal
时间窗: Through study completion, expected to be up to 88 weeks
Local reactogenicity following study product administration
时间窗: 14 days following each vaccination
Incidence and severity of solicited local reactogenicity signs and symptoms (injection site pain, erythema, and swelling), graded according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events
Number and description of adverse events (AEs) following study product administration
时间窗: 30 days following each vaccination
Systemic reactogenicity following study product administration
时间窗: 14 days following each vaccination
Incidence and severity of solicited systemic reactogenicity signs and symptoms (fever, fatigue, myalgia, arthralgia, headache, chills, nausea), graded according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events
Number and description of serious adverse events (SAEs)
时间窗: Through study completion, expected to be up to 88 weeks
Response rate of differential serum neutralizing antibody responses to precursor detection viruses
时间窗: At Baseline (Week 0) and 2 weeks after last vaccination
Proportion of participants with serum antibody responses demonstrating differential neutralization of precursor detection viruses and corresponding epitope knock-out mutant viruses, as measured by TZM-bl pseudovirus assay
Magnitude of differential serum neutralizing antibody responses to precursor detection viruses
时间窗: At Baseline (Week 0) and 2 weeks after last vaccination
Magnitude of serum antibody neutralization of precursor detection viruses and corresponding epitope knock-out mutant viruses, as measured by TZM-bl pseudovirus assay
Response rate of differential serum neutralizing antibody responses to precursor detection viruses after last vaccination and after ART restart
时间窗: 6 weeks after last vaccination and 8 weeks after ART restart
Proportion of participants with serum antibody responses demonstrating differential neutralization of precursor detection viruses and corresponding epitope knock-out mutant viruses, as measured by TZM-bl pseudovirus assay
Magnitude of differential serum neutralizing antibody responses to precursor detection viruses after last vaccination and after ART restart
时间窗: 6 weeks after last vaccination and 8 weeks after ART restart
Magnitude of serum antibody neutralization of precursor detection viruses and corresponding epitope knock-out mutant viruses, as measured by TZM-bl pseudovirus assay
次要结局
- Frequency of Env-specific and V3-glycan-specific B cells(At Baseline (Week 0) and 2 weeks after last vaccination)
- Frequency of mutation of V3-glycan-specific B-cell receptor (BCR) sequences(At Baseline (Week 0) and 2 weeks after last vaccination)
- Frequency of Env-specific and V3-glycan-specific B cells after last vaccination and after ART restart(6 weeks after last vaccination and 8 weeks after ART restart)
- Frequency of mutation of V3-glycan-specific B-cell receptor (BCR) sequences after last vaccination and after ART restart(6 weeks after last vaccination and 8 weeks after ART restart)
- Response rate of serum IgG binding antibodies to autologous HIV Env stabilized trimers(At Baseline (Week 0) and 2 weeks after last vaccination)
- Magnitude of serum IgG binding antibodies to autologous HIV Env stabilized trimers(At Baseline (Week 0) and 2 weeks after last vaccination)
- Epitope specificity of serum IgG binding antibodies to autologous HIV Env stabilized trimers(At Baseline (Week 0) and 2 weeks after last vaccination)
- Response rate of neutralization activity against heterologous tier 2 viruses(At Baseline (Week 0) and 2 weeks after last vaccination)
- Magnitude of neutralization activity against heterologous tier 2 viruses(At Baseline (Week 0) and 2 weeks after last vaccination)
- Breadth of neutralization activity against heterologous tier 2 viruses(At Baseline (Week 0) and 2 weeks after last vaccination)
- Response rate of serum IgG binding antibodies to autologous HIV Env stabilized trimers after last vaccination and after ART restart(6 weeks after last vaccination and 8 weeks after ART restart)
- Magnitude of serum IgG binding antibodies to autologous HIV Env stabilized trimers after last vaccination and after ART restart(6 weeks after last vaccination and 8 weeks after ART restart)
- Epitope specificity of serum IgG binding antibodies to autologous HIV Env stabilized trimers after last vaccination and after ART restart(6 weeks after last vaccination and 8 weeks after ART restart)
- Response rate of neutralization activity against heterologous tier 2 viruses after last vaccination and after ART restart(6 weeks after last vaccination and 8 weeks after ART restart)
- Magnitude of neutralization activity against heterologous tier 2 viruses after last vaccination and after ART restart(6 weeks after last vaccination and 8 weeks after ART restart)
- Breadth of neutralization activity against heterologous tier 2 viruses after last vaccination and after ART restart(6 weeks after last vaccination and 8 weeks after ART restart)
- Change in HIV Env sequence characteristics during ATI(During ATI)
- Change in HIV gag sequence characteristics during ATI(During ATI)