RENEW-SHCS: A Phase 1 Open-label Clinical Trial to Evaluate the Safety and Immunogenicity of Recombinant HIV-1 Env Protein BG505 SOSIP.GT1.1 gp140 Vaccine, Adjuvanted, in ARV-treated Adults Living With HIV Enrolled in the SHCS and to Restimulate and Newly Prime Antibody Responses.
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Safety - reactogenicity
研究概览
简要总结
A vaccine trial in which people with HIV-1 participating in the Swiss HIV Cohort Study will receive a HIV-specific vaccine to stimulate antibodies against HIV while continuing their standard antiretroviral therapy
详细描述
Vaccination of people with HIV (PWH) on suppressive antiretroviral therapy (ART) represents a novel approach for evaluating candidate broadly neutralizing antibody (bnAb) immunogens for preventive and therapeutic HIV vaccines. RENEW-SHCS is a phase I, open-label, non-randomized vaccination trial evaluating a single dose of the recombinant germline-targeting envelope trimer BG505 SOSIP.v4.1-GT1.1 (GT1.1), adjuvanted with 3M052-AF and Aluminum hydroxide (alum), in PWH on suppressive ART enrolled from the Swiss HIV Cohort Study. Participants were previously classified as bnAb or non-neutralizing antibody (nnAb) inducers, with a target enrollment of 15 per group, and are monitored for safety and immunogenicity for 24 weeks while continuing standard ART
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 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
- •Ability and willingness to provide informed consent.
- •Age ≥18 years at time of consent
- •People with HIV (PWH) with confirmed HIV-1 infection as documented by medical records and enrolled in the SHCS.
- •SHCS participants with known bnAb inducer- and non-neutralizing Ab inducer (nnAb inducer) status. (Note: Information on bnAb/nnAb status is available through SHCS-linked research prior to recruitment and has been obtained from analysis of SHCS biobanked plasma samples from off-ART and/or on-ART timepoints. Based on this information participant will be classified into bnAb inducers and nnAb inducers.)
- •On suppressive ART with plasma HIV-1 RNA <50 copies/ml for at least 1 year prior to screening. [Note: Intermittent blips (HIV-1 RNA between 50-200 copies) documented in prior years on ART are allowed but viral load at screening must be <50 copies. No switch to a novel ART regimen allowed 1 month before IMP administration. Switching from TDF to TAF and vice versa is not considered as switch to a novel regimen.]
- •CD4+ cell count > 250 cells/mm3 or CD4+ cell % ≥ 15% at screening (- 90 days prior to IMP administration)
- •At screening: Absolute neutrophil count (ANC) ≥ 750/mm3
- •At screening: Platelets ≥ 100,000/mm3
- •At screening: Alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN) based on the institutional normal range
- •At screening: Haemoglobin (Hgb):
- •≥ 10.0 g/dL for volunteers who were assigned female sex at birth (AFAB)
- •≥ 11.0 g/dL for cisgender volunteers who were assigned male sex at birth (AMAB) and for transgender men who have been on hormone therapy for more than 6 consecutive months
- •≥ 11.0 g/dL for transgender women who have been on hormone therapy for more than 6 consecutive months
- •For transgender volunteers who have been on hormone therapy for less than 6 consecutive months, determine Hgb eligibility based on their sex assigned at birth.
- •Persons of pregnancy potential
- •Must have a negative beta human chorionic gonadotropin (β-HCG) pregnancy test (urine or serum) on day 0 before IMP administration.
- •All participants born female who are engaging in sexual activity that could lead to pregnancy must commit to use of an effective method of contraception from 21 days before IMP administration to week 24 of the study.
- •Effective contraception includes condoms (male or female) with or without spermicide, diaphragm or cervical cap with spermicide, intrauterine device, hormonal contraception, including contraceptive implant or injectable, oral contraception, successful vasectomy in the male partner.
- •Participants born female do not have to use birth control if they are not engaging in sexual activity that could lead to pregnancy or are not of reproductive potential such as having undergone hysterectomy, bilateral oophorectomy, or tubal ligation, postmenopausal (amenorrhea for at least 1 year), surgically sterile.
排除标准
- •• Presence of other, HIV-unrelated, immunosuppression considered as relevant by the site investigator (e.g. a daily steroid intake of ≥20mg for 3 months is considered clinically relevant)
- •Ongoing signs and symptoms of a febrile illness at the time of the vaccination (temperature > 37.5°, and e.g. flu-like or other symptoms of a febrile illness)
- •Reduced health status due to other illnesses, which would not allow to participate in this study.
- •Volunteer who is pregnant or breast-feeding
- •Previous receipt of any anti-HIV monoclonal antibody or HIV vaccine.
- •Receipt of a non-HIV experimental vaccine(s) received within the last 6 months before IMP administration. Exceptions include vaccines that have subsequently undergone licensure or Emergency Use Authorization (EUA) by the FDA, World Health Organization (WHO) emergency use listing (EUL), Swissmedic licensure, European Medicines Agency (EMA) licensure.
- •Receipt of any other vaccine within 28 days prior to IMP administration (d0)
- •Is currently participating in or has participated in a clinical study with an investigational compound or device from in the last 45 days prior to Day 0 and throughout the study treatment period.
- •History of serious reaction (e.g., hypersensitivity, anaphylaxis) to any vaccine or component of the IMP
- •Asplenia or functional asplenia
- •Site investigator concern for difficulty with venous access based on clinical history and physical examination
研究组 & 干预措施
Single vaccination with recombinant BG505 SOSIP.GT1.1 gp140 vaccine
干预措施: The Patients will all receive a vaccination with a recombinant HIV-1 envelope protein BG505 SOSIP.GT1.1 gp140 vaccine, adjuvanted,. (Biological)
结局指标
主要结局
Safety - reactogenicity
时间窗: 7 days
Proportion of volunteers with Grade 2 or greater reactogenicity (i.e., solicited adverse events) from Day 0 through Day 7 after administration of investigational medical product (IMP).
Safety - IP related unsolicited adverse events
时间窗: 28 days
Proportion of volunteers with IP-related unsolicited adverse events (AEs), including safety laboratory (biochemical, hematological) parameters, from the day of IMP administration up to 28 days post administration
Safety - Grade 2 or greater unsolicited AEs
时间窗: 28 days
Proportion of volunteers with Grade 2 or greater unsolicited adverse events (AEs), including safety laboratory (biochemical, hematological) parameters, from the day of each IP administration up to 28 days post each IP administration
Safety - IMP related SAEs
时间窗: 168 days
Proportion of volunteers with IP-related serious adverse events (SAEs) throughout the study period
Safety - pIMDs
时间窗: 168 days
Proportion of volunteers with potential immune-mediated diseases (pIMDs) from the day of IMP administration throughout the study period
次要结局
- Immunogenicity - Frequency of Ab responses(From enrollment to the end of study observation at Day 168)
- Immunogenicity - Magnitude Ab responses(168 days)