A Phase I, Open Label Dose Escalation Study to Evaluate Safety of iHIVARNA-01 in Chronically HIV-infected Patients Under Stable Combined Antiretroviral Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicity (DLT)
研究概览
简要总结
The main purpose of the study is to evaluate the safety and to establish the recommended dose of iHIVARNA-01 as a new therapeutic vaccine against HIV
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient is ≥ 18 years of age
- •Voluntarily signed informed consent
- •Patient is male, or female with negative pregnancy test prior to enrolment
- •Patient has a proven HIV-1 infection (with positive antibodies against HIV-1 and a detectable plasma HIV-1 RNA before cART)
- •Patient must be on stable treatment with cART for at least 6 months (cART is defined as an antiretroviral regimen consisting of at least three registered antiretroviral agents)
- •Nadir CD4+ cell counts must be above or equal to 350 cells/μl (1 or 2 occasional determinations below 350 will be allowed)
- •Current CD4+ cell count must be at least 450 cells/μl
- •HIV-RNA must be below 50 copies/ mL for the last 6 months prior to inclusion, during at least two measurements (occasional so called 'blips' up to 50 copies/mL are permitted)
排除标准
- •Treatment with a non-cART regimen of antiretroviral agents prior to the start of cART;
- •History of a CDC class C event (see Appendix V);
- •Patient is female and has a positive pregnancy test or the wish of pregnancy:
- •Active opportunistic infection, or any active infection or malignancy within 30 days prior to screening visit;
- •Therapy with immunomodulatory agents, including cytokines (e.g. IL2) and gamma globulin, or cytostatic chemotherapy within 90 days prior to screening visit;
- •Use of anti-coagulant medication;
- •Use of any investigational drug during the 90 days prior to study entry;
- •Previous failure to antiretroviral and/or mutations conferring genotypic resistance to antiretroviral therapy EudraCT No. 2014-004591-32 33 Protocol version 1.1, dated 10 February 2015
- •Any other condition which, in the opinion of the investigator, may interfere with the evaluation of the study objectives.
- •Active hepatitis C virus or hepatitis B virus co-infection
- •Non-subtype B HIV infection
研究组 & 干预措施
100 μg TriMix mRNA (TriMix_100)
Cohort 1 (control group) 3 patients will receive 100 μg of mRNA (i.e. 100 μg TriMix mRNA).If two or more of the three patients have a dose limiting toxicity (DLT), DSMB should be consulted and study will be terminated. If one or no patients have a dose limiting toxicity, three patients will be enrolled at the next dose level.
Each patient will receive 3 immunizations (at weeks 0, 2 and 4).
干预措施: TriMix_100 (Biological)
300 μg TriMix mRNA (TriMix_300)
Cohort 2 (control group) 3 patients will receive 300 μg of mRNA (i.e. 100 μg TriMix mRNA).If two or more of the three patients have a DLT, DSMB should be consulted and study will be terminated. If one or no patients have a dose limiting toxicity, three patients will be enrolled at the next dose level.
Each patient will receive 3 immunizations (at weeks 0, 2 and 4).
干预措施: TriMix_300 (Biological)
600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA)
Cohort 3 (experimental group) 3 patients will receive 600 μg of mRNA (300 μg HIV mRNA + 300 μg TriMix mRNA). If two or more of the three patients have a DLT, DSMB should be consulted and study will be terminated. If one or no patients have a dose limiting toxicity, three patients will be enrolled at the next dose level.
Each patient will receive 3 immunizations (at weeks 0, 2 and 4).
干预措施: 600μg mRNA (300 μg HIV mRNA+300 μg TriMix mRNA) (Biological)
900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA)
Cohort 4 (experimental group) 3 patients will receive 900 μg of mRNA (i.e. 600 μg HIV mRNA and 300 μg TriMix mRNA). If two or more of the three first patients have a DLT, then additional three patients will be enrolled at the previous level dose (dose will be reduced to 600 μg of mRNA per vaccination). If one or no patients have a DLT, additional three patients will be enrolled at 900 μg dose level. If two or more of the six patients receiving 900 μg of mRNA have a DLT, then additional 3 patients will be enrolled at the previous level dose (dose will be reduced to 600 μg of mRNA per vaccination). If one or no patients of the six patients have a DLT, six patients will be enrolled at the next dose level.
Each patient will receive 3 immunizations (at weeks 0, 2 and 4).
干预措施: 900μg mRNA (600 μg HIV mRNA+300 μg TriMix mRNA) (Biological)
1200μg mRNA(900 μg HIV mRNA+300 μg TriMix mRNA)
Cohort 5 (experimental group) 6 patients will receive 1200 μg of mRNA (i.e. 900 μg HIV mRNA + 300 μg TriMix mRNA) in case one or no patients of the six patients at the previous dose level have a DLT.
Each patient will receive 3 immunizations (at weeks 0, 2 and 4).
干预措施: 1200μg mRNA (900 μg HIV mRNA+300 μg TriMix mRNA) (Biological)
结局指标
主要结局
Dose Limiting Toxicity (DLT)
时间窗: week 24
Safety as measured by dose limiting toxicity (DLT), defined as: * Grade 3 or above local adverse event (pain, cutaneous reactions including induration) * Grade 3 or above systemic adverse event (temperature, chills, headache, nausea, vomiting, malaise, and myalgia) * Grade 3 or above other clinical or laboratory adverse event confirmed at examination or on repeat testing respectively * Any event attributable to vaccination leading to discontinuation of the immunisation regimen
次要结局
- Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against IN Peptide Pools as Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24.(weeks 4, 6, 8 and 24)
- Secondary Endpoint: Immunogenicty - Changes in the Magnitude of Total HIV-1-specific Immune Response Against OUT Peptide Pools as Measured by ELISPOT at Abseline and Weeks 4, 6, 8 and 24 Measured by ELISPOT at Baseline and Weeks 4, 6, 8 and 24.(weeks 4, 6, 8 and 24)
- Secondary End Point: Effect on Reservoir(weeks 4, 6, 8 and 24)
研究者
Judit Pich Martínez
Clinical Research Manager
Fundacion Clinic per a la Recerca Biomédica