NCT03837756已完成2 期
Combining a TLR9 Agonist With Broadly Neutralizing Antibodies for Reservoir Reduction and Immunological Control of HIV Infection: An Investigator-initiated Randomized, Placebo-controlled, Phase IIa Trial.
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 8
- 主要终点
- Time to re-initiation of cART during analytical treatment interruption (ATI)
研究概览
简要总结
This study is designed to evaluate the safety and efficacy of lefitolimod and 3BNC117/10-1074 in HIV-1-infected individuals on ART and during ATI as intervention to reduce the HIV-1 reservoir
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
The participant and all study personnel who directly interact with study participants are blinded to study arm designation.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented HIV-1 infection
- •Adults age 18-65 years
- •On ART for a minimum of 18 months.
- •CD4+ T cell count >500 at screening
- •HIV-1 RNA plasma level of < 50 copies/mL by standard assays for at least 15 months (a single viral load measurement > 50 but < 500 copies/mL during this time period is allowable).
- •Able to give informed consent
- •Viral reservoir sensitivity to 3BNC117 and 10-
- •(Sensitivity of the viral reservoir to neutralization by 3BNC117 and 10-1074 will be tested following the screening visit (i.e. prior to randomization)).
- •Sensitivity of the viral reservoir to neutralization by 3BNC117 and 10-1074 will be tested following the screening visit (i.e. prior to enrollment and randomization). Isolated PBMCs will be analyzed using the PhenoSense HIV mAb Assay, Monogram Biosciences. The sensitivity of an individuals archieved proviruses to bNAb neutralization will be determined by the IC50 value of PBMC derived pseudovirus inhibition. Subjects that are considered sensitive to both 3BNC117 (IC90<=1.5 μg/mL) and 10-1074 (IC90<=2.0 μg/mL) AND MPI>97 AND fulfill the other inclusion/exclusion criteria will proceed to study enrolment and randomization.
- •If sensitivity cannot be determined by the PhenoSense HIVmAb Assay, participants will be screened for 3BNC117 and 10-1074 sensitivity using HIV env sequencing carried out in-house (Aarhus, Denmark). The method was originally established and validated by Rockefeller University that already has this method implemented. The method utilizes HIV-1 DNA envelope sequencing and a mathematical prediction binding algoritm of known binding sites of the antibodies. Based on the individual HIV env sequence, proviruses are categorized as "sensitive" or "resistant". Subjects that are determined to be sensitive to both 3BNC117 and 10-1074 (defined as at least 90% of known sequences sensitive to either bNAb) AND fulfill the other inclusion/exclusion criteria will proceed to study enrolment and randomization.
排除标准
- •Any significant acute medical illness requiring hospitalization in the past 4 weeks
- •Any evidence of an active AIDS-defining opportunistic infection
- •Any condition that, in the Investigator's opinion, will prevent adequate compliance with study therapy
- •The following laboratory values at screening, the values can be repeated within the screening period, but test results must be available before baseline (Day 0) and checked for eligibility: Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal (ULN) // Serum total bilirubin ≥3 ULN // Estimated glomerular filtration rate (eGFR) ≤50 mL/min (based on serum creatinine) // Platelet count ≤100 x109/L // Absolute neutrophil count ≤1x109/L
- •Hepatitis B or C infection
- •History of: Malignancy, excluding non-melanoma skin cancers, or organ transplantation
- •Receipt of strong immunosuppressive or systemic chemotherapeutic agents within 28 days prior to study entry
- •Known resistance to >2 classes of ART
- •Known hypersensitivity to the components of lefitolimod, 3BNC117, 10-1074 or their analogues
- •Pre-existing autoimmune or antibody-mediated diseases
- •Women who are pregnant or breastfeeding, or unwilling/ unable to use an acceptable method of contraception (if of child bearing potential)
- •Males or females who are unwilling or unable to use barrier contraception during sexual intercourse until plasma HIV-1 RNA is undetectable using standard assays
研究组 & 干预措施
Arm A: Placebo/Placebo
Placebo Comparator
This arm will receive placebo (sterile saline) for both Lefitolimod and 3BNC117 + 10-1074.
干预措施: Saline (Drug)
Arm B: Lefitolimod/Placebo
Active Comparator
This arm will receive Lefitolimod and placebo (sterile saline) for 3BNC117 + 10-1074.
干预措施: Saline (Drug)
Arm B: Lefitolimod/Placebo
Active Comparator
This arm will receive Lefitolimod and placebo (sterile saline) for 3BNC117 + 10-1074.
干预措施: Lefitolimod (Drug)
Arm C: Placebo/3BNC117 + 10-1074
Active Comparator
This arm will receive 3BNC117 + 10-1074 and placebo (sterile saline) for Lefitolimod.
干预措施: Saline (Drug)
Arm C: Placebo/3BNC117 + 10-1074
Active Comparator
This arm will receive 3BNC117 + 10-1074 and placebo (sterile saline) for Lefitolimod.
干预措施: 3BNC117 and 10-1074 (Drug)
Arm D: Lefitolimod/3BNC117 + 10-1074
Active Comparator
This arm will receive both Lefitolimod and 3BNC117 + 10-1074.
干预措施: Lefitolimod (Drug)
Arm D: Lefitolimod/3BNC117 + 10-1074
Active Comparator
This arm will receive both Lefitolimod and 3BNC117 + 10-1074.
干预措施: 3BNC117 and 10-1074 (Drug)
结局指标
主要结局
Time to re-initiation of cART during analytical treatment interruption (ATI)
时间窗: Up to 26 weeks.
Time from date of cART cessation to the date of the last of three consecutive plasma HIV-1 RNA measurements \>10,000 copies/mL, CD4 cell count \<350 on two consecutive measurements, or end of ATI (i.e. 26 weeks after cessation of cART) - whichever comes first.
次要结局
- Plasma HIV RNA doubling time(Duration of ATI (up to 26 weeks))
- Safety and Tolerability assessment measured by AEs, Adverse Reactions (ARs), SAEs,(Duration of the study)
研究者
研究点 (8)
Loading locations...
相似试验
进行中（未招募）
1 期
Combining a TLR9 agonist with broadly neutralizing antibodies forreservoir reduction and immunological control of HIV infection: Aninvestigator-initiated randomized, placebo-controlled, phase IIa trial(TITAN)EUCTR2018-001165-16-NODepartment of infectious Diseases, Aarhus University Hospital48
进行中（未招募）
1 期
Combining a TLR9 agonist with broadly neutralizing antibodies for reservoir reduction and immunological control of HIV infection: An investigator-initiated randomized, placebo-controlled, phase IIa trial (TITAN)HIV infectionMedDRA version: 20.1Level: LLTClassification code 10073675Term: HIV infection CDC category unspecifiedSystem Organ Class: 100000004862EUCTR2018-001165-16-DKDepartment of infectious Diseases, Aarhus University Hospital48
进行中（未招募）
2 期
MUK Nine b: OPTIMUM Treatment ProtocolMultiple MyelomaNCT03188172University of Leeds95
已完成
不适用
Effects of Two Anti-HIV Drug Combinations on the Immune Systems of HIV-Infected Patients Who Have Never Received Anti-HIV DrugsHIV InfectionsNCT00004855National Institute of Allergy and Infectious Diseases (NIAID)55
进行中（未招募）
1 期
Toll-like receptor 9 augmentation of antiviral immune responses to enhance the immune cell-mediated killing of HIV infected cells leading to a better clearance of the infectioHIVMedDRA version: 19.0Level: LLTClassification code 10073675Term: HIV infection CDC category unspecifiedSystem Organ Class: 100000004862EUCTR2014-005634-59-DKAarhus University Hospital16