A 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

Официальное название

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

Обзор

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.

Вмешательства

• Биопрепарат DV700P-RNA 100 mcg
  Intramuscular injection
• Биопрепарат DV701B1.1-RNA 100 mcg
  Intramuscular injection

Первичные конечные точки

• Local reactogenicity following study product administration [Срок оценки: 14 days following each vaccination]
• Systemic reactogenicity following study product administration [Срок оценки: 14 days following each vaccination]
• Number and description of serious adverse events (SAEs) [Срок оценки: Through study completion, expected to be up to 88 weeks]
• Number and description of medically attended adverse events (MAAEs) [Срок оценки: Through study completion, expected to be up to 88 weeks]
• Number and description of adverse events of special interest (AESIs) [Срок оценки: Through study completion, expected to be up to 88 weeks]
• Number and description of adverse events leading to study product discontinuation or participant withdrawal [Срок оценки: Through study completion, expected to be up to 88 weeks]
• Number and description of adverse events (AEs) following study product administration [Срок оценки: 30 days following each vaccination]
• Response rate of differential serum neutralizing antibody responses to precursor detection viruses [Срок оценки: At Baseline (Week 0) and 2 weeks after last vaccination]
• Magnitude of differential serum neutralizing antibody responses to precursor detection viruses [Срок оценки: At Baseline (Week 0) and 2 weeks after last vaccination]
• Response rate of differential serum neutralizing antibody responses to precursor detection viruses after last vaccination and after ART restart [Срок оценки: 6 weeks after last vaccination and 8 weeks after ART restart]

Вторичные конечные точки (12)

• Frequency of Env-specific and V3-glycan-specific B cells [Срок оценки: At Baseline (Week 0) and 2 weeks after last vaccination]
• Frequency of mutation of V3-glycan-specific B-cell receptor (BCR) sequences [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 6 weeks after last vaccination and 8 weeks after ART restart]
• Response rate of serum IgG binding antibodies to autologous HIV Env stabilized trimers [Срок оценки: At Baseline (Week 0) and 2 weeks after last vaccination]
• Magnitude of serum IgG binding antibodies to autologous HIV Env stabilized trimers [Срок оценки: At Baseline (Week 0) and 2 weeks after last vaccination]
• Epitope specificity of serum IgG binding antibodies to autologous HIV Env stabilized trimers [Срок оценки: At Baseline (Week 0) and 2 weeks after last vaccination]
• Response rate of neutralization activity against heterologous tier 2 viruses [Срок оценки: At Baseline (Week 0) and 2 weeks after last vaccination]
• Magnitude of neutralization activity against heterologous tier 2 viruses [Срок оценки: At Baseline (Week 0) and 2 weeks after last vaccination]
• Breadth of neutralization activity against heterologous tier 2 viruses [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 6 weeks after last vaccination and 8 weeks after ART restart]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

США · 12 центров

• Alabama CRS (Site ID: 31788) — Birmingham
• Bridge HIV CRS (Site#: 30305) — San Francisco
• The Ponce de Leon Center CRS (Site ID: 5802) — Atlanta
• The Hope Clinic of the Emory Vaccine Center CRS (Site #: 31440) — Decatur
• Beth Israel Deaconess Medical Center / BIDMC VCRS (Site ID: 32077) — Boston
• Brigham and Women's Hospital Vaccine CRS (BWH VCRS) (Site#: 30007) — Boston
• Columbia P&S CRS (Site#: 30329) — New York
• University of Rochester Vaccines to Prevent HIV Infection CRS (Site#: 31467) — Rochester
• … и ещё 4 центра

Перу · 4 центра

• Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales CRS (CITBM) - Unidad — Bellavista
• Via Libre CRS (Site ID: 31909) — Lima
• Barranco CRS (Site ID: 11301) — Lima
• San Miguel CRS (Site ID: 11302) — Lima

Zimbabwe · 2 центра

• Seke South CRS/30294 University of Zimbabwe -Clinical Trials Research Centre (UZ-CTRC) — Harare
• Spilhaus CRS/30314 University of Zimbabwe -Clinical Trials Research Centre (UZ-CTRC) — Harare

Аргентина · 1 центр

• Fundacion Huesped CRS (Site ID: 31957) — Buenos Aires

Идентификаторы

NCT: NCT07569029 · HVTN 808 · 39218

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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