출생 시 HIV가 없는 주산기 HIV 노출 유아에서 3M-052-AF + 명반이 첨가된 426c.Mod.Core-C4b 백신의 안전성과 면역원성 비교 (HVTN316)
출생 시 HIV가 없는 주산기 HIV 노출 유아에서 3M-052-AF + 명반으로 보강된 426c.Mod.Core-C4b 백신의 안전성과 면역원성을 평가하기 위한 1상 임상 시험
The purpose of this study is to evaluate the safety and immunogenicity of 426c.Mod.Core-C4b vaccine adjuvanted with 3M-052-AF + Alum in infants with perinatal HIV exposure who are without HIV at birth
연구 개요
상태
정황
상세 설명
This study will compare the safety and immunogenicity of an experimental HIV vaccine in infants with perinatal HIV exposure who are without HIV at birth. The study vaccine is called 426c.Mod.Core-C4b. The vaccine is mixed with an adjuvant called 3M-052-AF + Alum.
This study is divided into 2 parts: Part A and B. Part A has 4 groups, while Part B has 2 groups. Part A of the study is testing the vaccine alone or in combination with different doses of adjuvant. Part B is testing study vaccine and the safest dose of adjuvants from Part A versus placebo. Depending on their group, participants will receive 426c.Mod.Core-C4b, 426c.Mod.Core-C4b vaccine adjuvanted with 3M-052-AF + Alum, or a placebo by injection at Months 0, 3, and 7.
Additional study visits will occur at Day 1, Week 2, Month 3 1/2, Month 7 1/2, Month 10, Year 1, Year 1 1/2, and Year 1 3/4. Study visits may include physical exams, blood and saliva collection for the infants and questionnaires, counselling, blood, and optional breastmilk collection for the mothers of infants.
연구 유형
등록 (추정된)
단계
- 1단계
연락처 및 위치
연구 연락처
- 이름: Clinical Trials Manager
- 전화번호: (206) 667-4212
- 이메일: itindale@fredhutch.org
연구 장소
-
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Gauteng
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Soweto, Gauteng, 남아프리카, 1862
- Soweto HVTN CRS
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연락하다:
- Fatima Laher
- 전화번호: 27-11-9899700
- 이메일: laherf@phru.co.za
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연락하다:
- Leonie Kruger
- 전화번호: 27-11-9899700
- 이메일: krugerl@phru.co.za
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria: Mother
- Mother's age is at least 18 years and is willing and able to provide written informed consent for their and their infant's participation in this study
- Mother is in the second or third trimester of singleton pregnancy, as determined by a clinical exam or sonography and reported menstrual history
- Mother agrees to donate umbilical cord blood
- Mother has a planned Caesarian delivery at Chris Hani Baragwanath Academic Hospital (Soweto) and plans to remain in the area after delivery and through study duration
- Mother is determined by the site investigator to be in good overall health at the time of delivery based on medical history and physical exam
- Mother has a documented CD4 count of more than 350 cells/mcL at screening
- Mother has been on cART for at least 16 weeks prior to delivery and intends to continue with cART for the duration of breastfeeding
- Mother has a viral load of less than 400 copies/mL between 2 weeks before and 7 days after delivery
- Mother has access to the participating HVTN CRS and is willing to be followed for the planned duration of the study
- Mother demonstrates understanding of this study and is able and willing to complete the informed consent process and delivery with verbal demonstration of understanding of all questionnaire items answered incorrectly
- Mother agrees not to enroll either self or infant in another research study for the duration of the trial without prior approval of the HVTN 316 PSRT.
- Mother has confirmed positive HIV-1 status documented by medical records at any time during or prior to screening, and confirmed by the HVTN CRS by serology
Exclusion Criteria: Mother
- Any World Health Organization (WHO) grade IV illness within 1 year prior to study enrollment, as determined by the history and physical examination and review of the medical record (if available). These include HIV wasting syndrome; PJP pneumonia; cerebral toxoplasmosis; extrapulmonary cryptococcosis; progressive multifocal leukoencephalopathy; any disseminated endemic mycosis (histoplasmosis); candidiasis of the esophagus, trachea, bronchi, or lung; disseminated atypical mycobacteria; non-typhoid salmonella septicemia; extrapulmonary tuberculosis; lymphoma; and Kaposi's sarcoma.
- Prior participation in any HIV-1 vaccine or anti-HIV antibody-mediated prevention trial
- Receipt of any investigational agent during this pregnancy
- Receipt of blood products, immunoglobulin (Ig), or immunomodulating therapy within 45 days prior to, and the day of delivery
- Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with or serve as a contraindication to protocol adherence, assessment of infant safety or reactogenicity, or a volunteer's ability to give informed consent
- Any condition that places the newborn at higher risk of early-onset sepsis, such as concern for active maternal infection at delivery, as determined by local site investigators (eg, fever)
- Detectable hepatitis B surface antigen (HBsAg)
Inclusion Criteria: Infant
- Born via Caesarean delivery to a pregnant woman living with HIV-1 who meets all maternal inclusion/exclusion criteria listed above
- Estimated gestational age at birth is at least 37 weeks
Note: If gestational age at birth is not documented in the infant's available birth records, study staff may assess gestational age at the earliest possible opportunity during the screening period and use this assessment for purposes of eligibility determination.
- Weight at birth is at least 2.5 kg
- Has initiated ARV prophylaxis consistent with current site-specific standard of care
- Hemoglobin (HgB) more than 14.0 g/dL
- White blood cell (WBC) count ≥ 7,000 cells/mm3
- Platelets more than 100,000 cells/mm3
- Alanine aminotransferase (ALT) less than 1.25 times upper limit of age-adjusted normal
- Creatinine less than 1.1 times upper limit of age adjusted normal
- Negative HIV-1 nucleic acid test (NAT) on specimen drawn within 72 hours of birth
- Written informed consent provided by mother
- Age is equal to or less than 7 days
Exclusion Criteria: Infant
- Any clinically significant congenital anomaly/birth defect
- Documented or suspected serious medical illness, infection, clinically significant finding from physical examination, or immediate life-threatening condition, including requirement for ongoing supplemental oxygen, as judged by the examining clinician
- Receipt of or anticipated need for blood products, immunoglobulin, or immunosuppressive therapy. This includes infants who require hepatitis B immunoglobulin (HBIG), but it does not require exclusion of infants who receive hepatitis B vaccine in the newborn period.
- Receipt of any other investigational product
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 방지
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: Part A, Group 1: 426c.Mod.Core-C4b (20 mcg)
Participants will receive 426c.Mod.Core-C4b (20 mcg) alone to be administered as two 0.25-mL intramuscular (IM) doses, one into each thigh at weeks 0, 12, and 28. |
self-assembling nanoparticle expressing up to 7 molecules of the 426c.Mod.Core envelope immunogen. |
|
실험적: Part A, Group 2: 426c.Mod.Core-C4b (20 mcg) + 3M-052-AF (0.3 mcg) + Alum (250 mcg)
Participants will receive 426c.Mod.Core-C4b (20 mcg) admixed with 3M-052-AF (0.3 mcg) and aluminum hydroxide suspension (Alum) (250 mcg) to be administered as two 0.25-mL IM doses, one into each thigh at weeks 0, 12, and 28. |
self-assembling nanoparticle expressing up to 7 molecules of the 426c.Mod.Core envelope immunogen. 3M-052-AF is an aqueous formulation (AF) of a lipidated small molecule imidazoquinoline that is a Toll-like receptor (TLR)7/8 and inflammasome agonist. To be administered as 0.3 mcg, 0.75 mcg, or 1.5 mcg admixed with 426c.Mod.Core-C4b, with Alum Aluminum hydroxide suspension (Alum) to be administered as 250 mcg (aluminum content) admixed with 426c.Mod.Core-C4b with 3M-052-AF. |
|
실험적: Part A, Group 3: 426c.Mod.Core-C4b (20 mcg) + 3M-052-AF (0.75 mcg) + Alum (250 mcg)
Participants will receive 426c.Mod.Core-C4b (20 mcg) admixed with 3M-052-AF (0.75 mcg) and aluminum hydroxide suspension (Alum) (250 mcg) to be administered as two 0.25-mL IM doses, one into each thigh at weeks 0, 12, and 28. |
self-assembling nanoparticle expressing up to 7 molecules of the 426c.Mod.Core envelope immunogen. 3M-052-AF is an aqueous formulation (AF) of a lipidated small molecule imidazoquinoline that is a Toll-like receptor (TLR)7/8 and inflammasome agonist. To be administered as 0.3 mcg, 0.75 mcg, or 1.5 mcg admixed with 426c.Mod.Core-C4b, with Alum Aluminum hydroxide suspension (Alum) to be administered as 250 mcg (aluminum content) admixed with 426c.Mod.Core-C4b with 3M-052-AF. |
|
실험적: Part A, Group 4: 426c.Mod.Core-C4b (20 mcg) + 3M-052-AF (1.5 mcg) + Alum (250 mcg)
Participants will receive 426c.Mod.Core-C4b (20 mcg) admixed with 3M-052-AF (1.5 mcg) and aluminum hydroxide suspension (Alum) (250 mcg) to be administered as two 0.25-mL IM doses, one into each thigh at weeks 0, 12, and 28. |
self-assembling nanoparticle expressing up to 7 molecules of the 426c.Mod.Core envelope immunogen. 3M-052-AF is an aqueous formulation (AF) of a lipidated small molecule imidazoquinoline that is a Toll-like receptor (TLR)7/8 and inflammasome agonist. To be administered as 0.3 mcg, 0.75 mcg, or 1.5 mcg admixed with 426c.Mod.Core-C4b, with Alum Aluminum hydroxide suspension (Alum) to be administered as 250 mcg (aluminum content) admixed with 426c.Mod.Core-C4b with 3M-052-AF. |
|
활성 비교기: Part B, Group 5: 426c.Mod.Core-C4b (20 mcg) + 3M-052-AF (TBD)* + Alum (250 mcg)
Participants will receive 426c.Mod.Core-C4b (20 mcg) admixed with 3M-052-AF (TBD) and Alum (250 mcg) to be administered as two 0.25-mL IM doses, one into each thigh at weeks 0, 12, and 28. |
self-assembling nanoparticle expressing up to 7 molecules of the 426c.Mod.Core envelope immunogen. 3M-052-AF is an aqueous formulation (AF) of a lipidated small molecule imidazoquinoline that is a Toll-like receptor (TLR)7/8 and inflammasome agonist. To be administered as 0.3 mcg, 0.75 mcg, or 1.5 mcg admixed with 426c.Mod.Core-C4b, with Alum Aluminum hydroxide suspension (Alum) to be administered as 250 mcg (aluminum content) admixed with 426c.Mod.Core-C4b with 3M-052-AF. |
|
위약 비교기: Part B, Group 6: Placebo
Participants will receive Placebo (Tris Sodium Chloride (NaCl) buffer ) to be administered as two 0.25-mL IM doses, one into each thigh at weeks 0, 12, and 28. |
Tris-NaCl buffer. |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Number of participants reporting local reactogenicity signs and symptoms and number of local reactogenicity signs and symptoms experienced by each participant
기간: Measured through 14 days following receipt of study product at day 5, week 12, and week 28
|
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017] |
Measured through 14 days following receipt of study product at day 5, week 12, and week 28
|
|
Number of participants reporting systemic reactogenicity signs and symptoms symptoms and number of systemic reactogenicity signs and symptoms experienced by each participant,
기간: Measured through 14 days following receipt of study product at day 5, week 12, and week 28
|
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017] |
Measured through 14 days following receipt of study product at day 5, week 12, and week 28
|
|
Number of participants reporting adverse events and overall number of adverse events
기간: Measured through out the study period
|
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017] |
Measured through out the study period
|
|
Number of participants reporting serious adverse events and overall number of serious adverse events
기간: Measured through 12 months post last vaccination at week 28
|
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017] |
Measured through 12 months post last vaccination at week 28
|
|
Number of participants reporting medically attended adverse events and overall number of medically attended adverse events
기간: Measured through 12 months post last vaccination at week 28
|
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017] |
Measured through 12 months post last vaccination at week 28
|
|
Number of participants reporting adverse events of special interest (AESIs) that are Potential Immune Mediated Medical Conditions (PIMMCs) and overall number of AESIs that are PIMMCs
기간: Measured through 12 months post last vaccination at week 28
|
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017] |
Measured through 12 months post last vaccination at week 28
|
|
Number of participants reporting AEs leading to early participant withdrawal or permanent discontinuation
기간: Measured through 12 months post last vaccination at week 28
|
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [March 2017] |
Measured through 12 months post last vaccination at week 28
|
|
Response rate of CD4bs-specific IgG binding antibodies
기간: Measured 2 weeks after the 3rd vaccination at week 28
|
Measured by binding antibody multiplex assay (BAMA) |
Measured 2 weeks after the 3rd vaccination at week 28
|
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Magnitude of CD4bs-specific IgG binding antibodies
기간: Measured 2 weeks after the 3rd vaccination at week 28
|
Measured by binding antibody multiplex assay (BAMA) |
Measured 2 weeks after the 3rd vaccination at week 28
|
|
Response rate of CD4bs-specific memory B cells
기간: Measured 2 weeks after the 3rd vaccination at week 28
|
Measured by flow cytometry |
Measured 2 weeks after the 3rd vaccination at week 28
|
|
Magnitude of CD4bs-specific memory B cells
기간: Measured 2 weeks after the 3rd vaccination at week 28
|
Measured by flow cytometry |
Measured 2 weeks after the 3rd vaccination at week 28
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Response rate of serum Ab neutralization of vaccine-matched viruses
기간: Measured 2 weeks after the 3rd vaccination at week 28
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Measured by TZM-bl pseudoneutralization assay |
Measured 2 weeks after the 3rd vaccination at week 28
|
|
Magnitude of serum Ab neutralization of vaccine-matched viruses
기간: Measured 2 weeks after the 3rd vaccination at week 28
|
Measured by TZM-bl pseudoneutralization assay |
Measured 2 weeks after the 3rd vaccination at week 28
|
|
Differential neutralization of HIV-1 strains that are diagnostic for CD4bs bNAb precursors
기간: Measured 2 weeks after the 3rd vaccination at week 28
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Measured by TZM-bl assay |
Measured 2 weeks after the 3rd vaccination at week 28
|
|
Response rate of serum Ab neutralization of heterologous HIV-1 strains
기간: Measured 2 weeks after the 3rd vaccination at week 28
|
Measured by TZM-bl assay |
Measured 2 weeks after the 3rd vaccination at week 28
|
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Magnitude of serum Ab neutralization of heterologous HIV-1 strains
기간: Measured 2 weeks after the 3rd vaccination at week 28
|
Measured by TZM-bl assay |
Measured 2 weeks after the 3rd vaccination at week 28
|
|
Response rate (i.e., percentage) of CD4bs-specific, including VRC01-class, B cells
기간: Measured 2 weeks after the 3rd vaccination at week 28
|
Measured by BCR sequencing of sorted B cells |
Measured 2 weeks after the 3rd vaccination at week 28
|
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Magnitude of CD4bs-specific, including VRC01-class, B cells
기간: Measured 2 weeks after the 3rd vaccination at week 28
|
Measured by BCR sequencing of sorted B cells |
Measured 2 weeks after the 3rd vaccination at week 28
|
|
Response rate of vaccine-specific and CD4bs-specific binding antibodies
기간: Measured 6 months and 12 months after the 3rd vaccination at week 28
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Measured by BAMA |
Measured 6 months and 12 months after the 3rd vaccination at week 28
|
|
Magnitude of vaccine-specific and CD4bs-specific binding antibodies
기간: Measured 6 months and 12 months after the 3rd vaccination at week 28
|
Measured by BAMA |
Measured 6 months and 12 months after the 3rd vaccination at week 28
|
|
Response rate of CD4bs-specific memory B cells
기간: Measured 6 months and 12 months after the 3rd vaccination at week 28
|
Measured by flow cytometry |
Measured 6 months and 12 months after the 3rd vaccination at week 28
|
|
Response rate of serum neutralization
기간: Measured 6 months and 12 months after the 3rd vaccination at week 28
|
Measured by TZM-bl assay |
Measured 6 months and 12 months after the 3rd vaccination at week 28
|
|
Magnitude of serum neutralization
기간: Measured 6 months and 12 months after the 3rd vaccination at week 28
|
Measured by TZM-bl assay |
Measured 6 months and 12 months after the 3rd vaccination at week 28
|
|
EPI vaccine-specific binding antibody responses
기간: Measured 2 weeks, 6 months, and 12 months after the 3rd vaccination at week 28
|
Assessed by Pediatric Vaccine Multiplex Assay (PVMA) |
Measured 2 weeks, 6 months, and 12 months after the 3rd vaccination at week 28
|
공동 작업자 및 조사자
협력자
수사관
- 연구 의자: Amy Violari, Perinatal HIV Research Unit
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
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