Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of an Ad26.Mos4.HIV and CH505 TF chTrimer (Env) Combination to Mimic Acute HIV Viral Replication Kinetics in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Occurrence and severity of solicited local and systemic adverse events (AEs) following candidate vaccine administration
研究概览
简要总结
This is a Phase I, randomized, double-blind, placebo-controlled clinical study to define the safety and immunogenicity resulting from a rapid dose-escalating vaccination schedule as compared to that of a co-administered, dose-consistent vaccination schedule. Participants randomized to receive vaccines will get either dose-consistent injections of CH505 TF chTrimer+ALFQ co-administered with Ad26.Mos4.HIV or rapid, dose-escalating injections of CH505 TF chTrimer+ALFQ with an Ad26.Mos4.HIV prime, followed by dose-consistent injection of CH505 TF chTrimer+ALFQ co-administered with Ad26.Mos4.HIV
详细描述
This study is exploratory and will be a randomized, placebo-controlled, double-blind trial. A total of 78 healthy male and female participants, aged 18 to 50 years, who are at low risk for Human Immunodeficiency Virus (HIV) acquisition will be enrolled and randomized across four Arms (1a, 2a, 1b, and 2b). Enrollment will be completed in two parts, dubbed Part A and Part B. In Part A, up to 28 participants will be randomized across Arms 1a and 2a, with up to 14 participants per Arm. Within these Arms, participants will be randomized 11:3 to active vaccine versus placebo (normal saline) and followed for up to 18 months. In Part B, participants will be randomized across Arms 1b and 2b, with 25 individuals per Arm. Within these Arms, participants will be randomized 4:1 to active study vaccine versus placebo (normal saline) and followed for up to 18 months. All products will be administered by intramuscular (IM) injection into the same quadriceps muscle at each product administration visit.
Participants randomized to receive active study vaccines in Arm 1a will receive dose-consistent injections of Ad26.Mos4.HIV (5x1010 viral particles [vp]/0.5 mL) and CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) co administered on Study Days 1 and 57, followed by a dose-consistent injection of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) on Day 169.
Participants randomized to receive active study vaccines in Arm 2a will receive a lower dose of Ad26.Mos4.HIV (2.5x1010 vp/0.25 mL) and CH505 TF chTrimer (30 µg)+ALFQ (50 µg MPLA/25 µg QS 21) on Study Day 1, followed by rapid dose escalating injections of CH505 TF chTrimer (100 µg, 150 µg, and 300 µg)+ALFQ (50 µg MPLA/25 µg QS 21) through Study Day 15, followed by injections of Ad26.Mos4.HIV (5x1010 vp/0.5 mL) and CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) on Study Day 57, followed by an injection of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) on Study Day 169.
Participants randomized to receive active study vaccines in Arm 1b will have a similar dosing regimen as participants in Arm 1a but without Ad26.Mos4.HIV on Study Days 1 and 57.
Participants randomized to receive active study vaccines in Arm 2b will have a similar dosing regimen as participants in Arm 2a but without Ad26.Mos4.HIV on Study Days 1 and 57.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants must meet all of the following criteria to be eligible for participation:
- •Male or female, aged 18 to 50 years, inclusive, at the time of enrollment
- •Willing and able to read, sign, and date the informed consent form
- •Demonstrates an understanding of the study with a passing score (90% or greater) on the TOU by the third attempt, before study-related procedures are performed
- •Willing and able to comply with study requirements and be available to attend visits for the duration of study participation
- •Must have the means to be contacted by telephone for the duration of study participation
- •Willing to have photo or fingerprint taken for identification purposes
- •At low risk for HIV acquisition per investigator assessment
- •Agrees to refrain from donating blood or plasma outside of this study for at least the duration of study participation
- •Healthy based on the physician investigator's clinical judgment after review of past medical history, medication use, vital signs, and an abbreviated physical examination
- •Note: Good health is defined by the absence of any medical condition described in the exclusion criteria in a participant with a normal abbreviated physical exam and vital signs. If the participant has a preexisting chronic condition not listed in the exclusion criteria, the condition cannot meet any of the following criteria:
- •first diagnosed within the 12 weeks prior to screening; or
- •worsening in terms of clinical outcome in the 24 weeks prior to screening; or
- •involves the need for medication that may pose a risk to the participant's safety or impede assessment of adverse events or immunogenicity if they participate in the study.
- •Note: Vital signs must be normal by Adverse Event Grading Scales, local normal ranges, or determined to be a normal variant by the physician investigator.
- •Note: An abbreviated physical exam differs from a complete exam in that it does not include a genitourinary and rectal exam.
- •Laboratory criteria within 45 days prior to enrollment:
- •Hemoglobin ≥11.0 g/dL for females; ≥12.5 g/dL for males
- •White blood cells (WBC) range: 3,500-9,000 cells/mm^3
- •Platelets between 150,000 - 450,000 cells/µL
- •Normal liver function: Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤1.25x upper limit of normal
- •Serum creatinine ≤1.25x upper limit of normal
- •Urinalysis: blood and protein less than 1+ and negative glucose
- •Negative HIV serology Note: HIV serology testing will be done via enzyme immunoassay with confirmatory testing of reactive results through a repeat enzyme immunoassay followed by an antibody differentiation immunoassay. After the repeat enzyme immunoassay, if an antibody differentiation immunoassay cannot be done for any reason, then confirmatory testing will be done via Western Blot. HIV rapid testing will not be performed in this study.
- •Negative hepatitis B surface antigen (HbsAg)
- •Negative hepatitis C serology or negative hepatitis C RNA (viral load) if antibodies are detected Note: Each laboratory screening test that is out of acceptable range can be repeated one time during the screening window if there is a possible alternative explanation for the out of range value or if the out of range value is due to a temporary condition that resolves within the screening visit window. A second screening visit may be conducted outside of the initial screening visit window for volunteers who meet certain criteria if study enrollment and/or participant replacement is ongoing.
- •Biological Male-Specific Criteria:
- •Must agree to refrain from donating sperm from screening until at least 12 weeks after the last study injection
- •Must agree to consistently use a method of contraception from screening until at least 12 weeks after the last study injection
- •Biological Female-Specific Criteria:
- •Not pregnant within 12 weeks prior to screening, not pregnant or breastfeeding at screening, and not planning to become pregnant or breastfeed at any time from screening until 12 weeks after the last study injection
- •Must have a negative human chorionic gonadotropin (β-HCG) pregnancy test (urine) at screening and at timepoints throughout the study, if of childbearing potential
- •Must agree to consistently practice a highly effective method of contraception at least 45 days prior to enrollment and for 12 weeks after the final injection, if of childbearing potential
排除标准
- •Volunteers will be excluded if any of the following apply:
- •Body mass index (BMI) <18.0 kg/m^2 and >35.1 kg/m^2
- •Has a condition which affects immune function, including but not limited to:
- •Known or suspected congenital or acquired immunodeficiency
- •Diabetes mellitus type 1 or type 2 (including cases controlled with diet alone) Note: A history of isolated gestational diabetes is not an exclusion criterion.
- •Thyroid disease
- •Asplenia, defined as any condition resulting in the absence of a functional spleen
- •Conditions and diagnoses defined as potential immune-mediated medical conditions
- •Has a history of other chronic or clinically significant diseases or medical conditions that in the opinion of the investigator would jeopardize the safety or rights of the participant Note: Includes but is not limited to sickle cell anemia, chronic hepatitis or cirrhosis, chronic urticaria, chronic cardiac disease, hypertension not controlled by medication, severe asthma, chronic pulmonary disease, renal failure, and lymphatic filariasis.
- •Has a history of malignancy other than squamous cell or basal cell skin cancer, unless there has been definitive surgical and/or medical treatment that is considered to have achieved a cure
- •Had major surgery (per the physician investigator's judgment) within the 28 days prior to screening or has plans to have major surgery during the study
- •Has a personal or family history of a bleeding disorder, such as factor deficiency, coagulopathy, or platelet disorder requiring special precautions
- •Has a personal or family history of a blood clotting disorder, such as thrombosis with thrombocytopenia syndrome (TTS), heparin-induced thrombocytopenia and thrombosis (HITT), deep vein thrombosis, pulmonary embolism, acute myocardial infarction, and stroke
- •Has a condition known to increase risk of blood clotting, including but not limited to autoimmune disease, connective tissue and other inflammatory conditions, immobility, recent infection, and recent head trauma including cerebrovascular accidents (stroke)
- •Hepatitis B surface antigen positive at any time in the past
- •Untreated syphilis infection as confirmed by RPR or a similar quantitative nontreponemal test such as VDRL
- •Prior receipt or plans to receive any of the following:
- •Chronic use of therapies that may modify immune response, such as high dose inhaled and sprayed corticosteroids (>440 µg/twice daily doses of inhaled fluticasone equivalent) and systemic corticosteroids (>20 mg/day doses of prednisone equivalent for periods exceeding 10 days) within 14 days prior to enrollment or at any time during participation in this study Note: The following exceptions are permitted and will not exclude study participation: use of stable low/medium doses (<440 µg/twice daily doses of inhaled fluticasone equivalent) of inhaled and sprayed corticosteroids, topical corticosteroids for an acute uncomplicated dermatitis; or a short course (duration of 10 days or less, or a single injection) of corticosteroid for a non-chronic condition (based on the physician investigator's clinical judgment) at least 14 days prior to enrollment in this study. Includes other medications, which, in the opinion of the physician investigator(s), will impact the participant's immune response.
- •Blood products within 120 days prior to enrollment or at any time during participation in this study
- •Immunoglobulins within 90 days prior to enrollment or at any time during participation in this study
- •Therapy for active tuberculosis within 90 days prior to enrollment, unless the therapy is considered to have achieved a cure, or at any time during participation in this study
- •Licensed or authorized vaccine from 30 days prior to enrollment until 42 days (6 weeks) after the last study injection Note: Participants may receive inactivated seasonal influenza vaccine or COVID-19 vaccine during their participation in this study but not within 14 days prior or 6 weeks after each study injection
- •Any investigational study products for conditions other than HIV within 90 days prior to enrollment or at any time during participation in this study
- •An investigational HIV vaccine or HIV antibody at any time prior to or during participation in this study
- •Medications that increase the risk of bleeding (warfarin, clopidogrel, ticagrelor, dabigatran, rivaroxaban, apixaban, heparin and other heparinoids) or blood clots (heparin in participants who have a prior history of heparin-induced coagulopathy) within 30 days prior to enrollment or at any time during participation in this study. [Note: Volunteers determined to be ineligible at screening due to receipt of the above listed substances may be re-screened once the applicable window of receipt has expired if study enrollment and/or participant replacement is ongoing].
- •Has a known allergy or history of anaphylaxis or other serious reaction to a vaccine, vaccine component, or latex
- •Current or planned participation in another study requiring blood draws or exposure to investigational or non-investigational vaccine/product (pharmaceutical or device) throughout the study period
- •Has tattoos, scars, or other marks that would, in the opinion of the physician investigator, interfere with the assessment of the injection sites
- •Current or history of substance abuse within 12 months prior to enrollment that, in the physician investigator's opinion, could interfere with reliable participation
- •In the physician investigator's opinion, is unable to communicate reliably, is unlikely to adhere to study requirements, or has a condition that would limit completion of the study
- •Any other chronic or clinically significant medical condition that in the opinion of investigator would jeopardize the safety or rights of the participant or potentially impairs immune response or threatens conduct of the study according to protocol
- •Study site employee
- •Final evaluation of eligibility will be based on the medical judgment of the physician investigator.
研究组 & 干预措施
Ad26.Mos4.HIV and CH505 TF chTrimer + ALFQ [Arm 1a]
Arm 1a [Co-administration]: Dose consistent injections (5x10^10 vp/0.5 mL) of Ad26.Mos4.HIV in a 0.5 mL injection volume and dose consistent injections of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS-21) in a 1.1 mL injection volume on Study Days 1 and 57, followed by a dose-consistent injection of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) in a 1.1 mL injection volume on Study Day 169 (11 participants) OR a 0.5 mL injection and a 1.1 mL injection of Placebo on Study Days 1 and 57, followed by a 1.1 mL injection of Placebo on Study Day 169 (3 participants)
干预措施: Ad26.Mos4.HIV in CH505 TF chTrimer + ALFQ [Arm 1a] (Biological)
Ad26.Mos4.HIV and CH505 TF chTrimer + ALFQ [Arm 1a]
Arm 1a [Co-administration]: Dose consistent injections (5x10^10 vp/0.5 mL) of Ad26.Mos4.HIV in a 0.5 mL injection volume and dose consistent injections of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS-21) in a 1.1 mL injection volume on Study Days 1 and 57, followed by a dose-consistent injection of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) in a 1.1 mL injection volume on Study Day 169 (11 participants) OR a 0.5 mL injection and a 1.1 mL injection of Placebo on Study Days 1 and 57, followed by a 1.1 mL injection of Placebo on Study Day 169 (3 participants)
干预措施: CH505 TF chTrimer + ALFQ [Arm 1a] (Biological)
Ad26.Mos4.HIV and CH505 TF chTrimer + ALFQ [Arm 1a]
Arm 1a [Co-administration]: Dose consistent injections (5x10^10 vp/0.5 mL) of Ad26.Mos4.HIV in a 0.5 mL injection volume and dose consistent injections of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS-21) in a 1.1 mL injection volume on Study Days 1 and 57, followed by a dose-consistent injection of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) in a 1.1 mL injection volume on Study Day 169 (11 participants) OR a 0.5 mL injection and a 1.1 mL injection of Placebo on Study Days 1 and 57, followed by a 1.1 mL injection of Placebo on Study Day 169 (3 participants)
干预措施: Placebo [Arm 1a] (Biological)
CH505 TF chTrimer + ALFQ [Arm 1b]
Arm 1b [Trimer Bolus Administration]: Dose consistent injections of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS-21) in a 1.1 mL injection volume on Study Days 1, 57, and 169 (20 participants) OR a 1.1 mL injection of Placebo on Study Days 1, 57, and 169 (5 participants)
干预措施: CH505 TF chTrimer + ALFQ [Arm 1b] (Biological)
CH505 TF chTrimer + ALFQ [Arm 1b]
Arm 1b [Trimer Bolus Administration]: Dose consistent injections of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS-21) in a 1.1 mL injection volume on Study Days 1, 57, and 169 (20 participants) OR a 1.1 mL injection of Placebo on Study Days 1, 57, and 169 (5 participants)
干预措施: Placebo [Arm 1b] (Biological)
Ad26.Mos4.HIV and CH505 TF chTrimer + ALFQ [Arm 2a]
Arm 2a [Rapidvax]: A lower dose of Ad26.Mos4.HIV (2.5x10^10 vp/0.25mL) in a 0.25mL injection volume (InjV) + lower dose of CH505 TF chTrimer (30 µg)+ALFQ (50µg MPLA/25µg QS-21) in a 0.5mL InjV [Study Day (SD) 1]; followed by rapid, dose escalating injections of CH505 TF chTrimer (100µg, 150µg, and 300µg)+ALFQ (50µg MPLA/25µg QS-21) on SD's 4, 8 (0.5mL InjV), and 15 (0.9mL InjV); followed by injections of Ad26.Mos4.HIV (5x10^10 vp/0.5mL) in a 0.5mL InjV + CH505 TF chTrimer (300µg)+ALFQ (200µg MPLA/100µg QS 21) in a 1.1mL InjV on SD 57; followed by an injection of CH505 TF chTrimer (300µg)+ALFQ (200µg MPLA/100µg QS 21) in a 1.1mL InjV on SD 169 (11 participants) OR a 0.25mL injection and a 0.5mL injection of Placebo [P] on SD 1; followed by 0.5mL, 0.5mL, and 0.9 mL injections of [P] on SD's 4, 8, and 15, respectively; followed by a 0.5mL injection + 1.1mL injection of [P] on SD 57; followed by a 1.1mL injection of [P] on SD 169 (3 participants)
干预措施: Ad26.Mos4.HIV in CH505 TF chTrimer +ALFQ [Arm 2a] (Biological)
Ad26.Mos4.HIV and CH505 TF chTrimer + ALFQ [Arm 2a]
Arm 2a [Rapidvax]: A lower dose of Ad26.Mos4.HIV (2.5x10^10 vp/0.25mL) in a 0.25mL injection volume (InjV) + lower dose of CH505 TF chTrimer (30 µg)+ALFQ (50µg MPLA/25µg QS-21) in a 0.5mL InjV [Study Day (SD) 1]; followed by rapid, dose escalating injections of CH505 TF chTrimer (100µg, 150µg, and 300µg)+ALFQ (50µg MPLA/25µg QS-21) on SD's 4, 8 (0.5mL InjV), and 15 (0.9mL InjV); followed by injections of Ad26.Mos4.HIV (5x10^10 vp/0.5mL) in a 0.5mL InjV + CH505 TF chTrimer (300µg)+ALFQ (200µg MPLA/100µg QS 21) in a 1.1mL InjV on SD 57; followed by an injection of CH505 TF chTrimer (300µg)+ALFQ (200µg MPLA/100µg QS 21) in a 1.1mL InjV on SD 169 (11 participants) OR a 0.25mL injection and a 0.5mL injection of Placebo [P] on SD 1; followed by 0.5mL, 0.5mL, and 0.9 mL injections of [P] on SD's 4, 8, and 15, respectively; followed by a 0.5mL injection + 1.1mL injection of [P] on SD 57; followed by a 1.1mL injection of [P] on SD 169 (3 participants)
干预措施: CH505 TF chTrimer +ALFQ [Arm 2a] (Biological)
Ad26.Mos4.HIV and CH505 TF chTrimer + ALFQ [Arm 2a]
Arm 2a [Rapidvax]: A lower dose of Ad26.Mos4.HIV (2.5x10^10 vp/0.25mL) in a 0.25mL injection volume (InjV) + lower dose of CH505 TF chTrimer (30 µg)+ALFQ (50µg MPLA/25µg QS-21) in a 0.5mL InjV [Study Day (SD) 1]; followed by rapid, dose escalating injections of CH505 TF chTrimer (100µg, 150µg, and 300µg)+ALFQ (50µg MPLA/25µg QS-21) on SD's 4, 8 (0.5mL InjV), and 15 (0.9mL InjV); followed by injections of Ad26.Mos4.HIV (5x10^10 vp/0.5mL) in a 0.5mL InjV + CH505 TF chTrimer (300µg)+ALFQ (200µg MPLA/100µg QS 21) in a 1.1mL InjV on SD 57; followed by an injection of CH505 TF chTrimer (300µg)+ALFQ (200µg MPLA/100µg QS 21) in a 1.1mL InjV on SD 169 (11 participants) OR a 0.25mL injection and a 0.5mL injection of Placebo [P] on SD 1; followed by 0.5mL, 0.5mL, and 0.9 mL injections of [P] on SD's 4, 8, and 15, respectively; followed by a 0.5mL injection + 1.1mL injection of [P] on SD 57; followed by a 1.1mL injection of [P] on SD 169 (3 participants)
干预措施: Placebo [Arm 2a] (Biological)
CH505 TF chTrimer + ALFQ [Arm 2b]
Arm 2b [Trimer Rapidvax]: A lower dose of CH505 TF chTrimer (30 µg)+ALFQ (50 µg MPLA/25 µg QS 21) in a 0.5 mL injection volume on Study Day 1; followed by rapid, dose escalating injections of CH505 TF chTrimer (100 µg, 150 µg, and 300 µg)+ALFQ (50 µg MPLA/ 25 µg QS-21) on Study Days 4 (0.5 mL injection volume), 8 (0.5 mL injection volume), and 15 (0.9 mL injection volume); followed by injections of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) in a 1.1 mL injection volume on Study Days 57 and 169 (20 participants); OR a 0.5 mL injection of Placebo on Study Days 1, 4, and 8; followed by a 0.9 mL injection of Placebo on Study Day 15; followed by a 1.1 mL injection of Placebo on Study Days 57 and 169 (5 participants)
干预措施: CH505 TF chTrimer + ALFQ [Arm 2b] (Biological)
CH505 TF chTrimer + ALFQ [Arm 2b]
Arm 2b [Trimer Rapidvax]: A lower dose of CH505 TF chTrimer (30 µg)+ALFQ (50 µg MPLA/25 µg QS 21) in a 0.5 mL injection volume on Study Day 1; followed by rapid, dose escalating injections of CH505 TF chTrimer (100 µg, 150 µg, and 300 µg)+ALFQ (50 µg MPLA/ 25 µg QS-21) on Study Days 4 (0.5 mL injection volume), 8 (0.5 mL injection volume), and 15 (0.9 mL injection volume); followed by injections of CH505 TF chTrimer (300 µg)+ALFQ (200 µg MPLA/100 µg QS 21) in a 1.1 mL injection volume on Study Days 57 and 169 (20 participants); OR a 0.5 mL injection of Placebo on Study Days 1, 4, and 8; followed by a 0.9 mL injection of Placebo on Study Day 15; followed by a 1.1 mL injection of Placebo on Study Days 57 and 169 (5 participants)
干预措施: Placebo [Arm 2b] (Biological)
结局指标
主要结局
Occurrence and severity of solicited local and systemic adverse events (AEs) following candidate vaccine administration
时间窗: Day 0 - Day 505
Occurrence and severity of solicited local and systemic adverse events (AEs) following candidate vaccine administration.
Occurrence, severity, and relationship to vaccination of unsolicited adverse events after candidate vaccine administration
时间窗: Day 0 - Day 505
Occurrence, severity, and relationship to vaccination of unsolicited adverse events after candidate vaccine administration.
Occurrence of serious adverse events (SAEs) following candidate vaccine administration
时间窗: Day 0 - Day 505
Occurrence of serious adverse events (SAEs) following candidate vaccine administration.
Occurrence of adverse events of special interest (AESIs) following candidate vaccine administration
时间窗: Day 0 - Day 505
Occurrence of adverse events of special interest (AESIs) following candidate vaccine administration.
次要结局
- Quantify IgG binding antibodies to HIV Env in terms of magnitude, breadth, and durability between Arms(Visit Days 1, 4, 8, 15, 29, 57, 71, 85,169, 183, and 337)
- Quantify neutralizing antibodies to HIV Env in terms of magnitude, breadth, and durability between Arms(Visit Days 1, 4, 8, 15, 29, 57, 71, 85,169, 183, and 337)