건강한 미국 및 아프리카 성인에서 광범위한 중화 항체, 3BNC117-LS-J 및 10-1074-LS-J 조합의 안전성 및 약동학
This is a Phase 1/2 study to evaluate the safety, tolerability, and pharmacokinetics of two broadly neutralizing monoclonal human antibodies (bNAbs), 3BNC117-LS-J, which targets the CD4 binding site on HIV-1 envelope protein, and 10-1074-LS-J which targets the V3 loop of HIV-1 envelope protein. The hypothesis is that the two antibodies will be safe for healthy HIV-1 uninfected adults when co-administered subcutaneously or intravenously and, after subcutaneous administration in the optimal ratio, each antibody will maintain serum levels >10 µg/ml for at least 3 months in HIV-uninfected participants.
연구 개요
상태
정황
연구 유형
등록 (실제)
단계
- 2 단계
- 1단계
연락처 및 위치
연구 장소
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Johannesburg, 남아프리카
- Wits Reproductive Health and HIV Institute
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Kigali, 르완다
- Center for Family Health Research
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Massachusetts
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Boston, Massachusetts, 미국, 02115
- Brigham and Women's Hospital
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New York
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New York, New York, 미국, 10065
- The Rockefeller University
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Washington
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Seattle, Washington, 미국, 98109
- Fred Hutchinson Cancer Research Center
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Entebbe, 우간다
- Uganda Virus Research Institute
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Kampala, 우간다
- Infectious Diseases Institute Kasangati
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Nairobi, 케냐
- Kenya AIDS Vaccine Initiative - Institute of Clinical Research
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Kiambu County
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Thika, Kiambu County, 케냐
- Partners in Health Research and Development
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Healthy male and female individuals, as assessed by a medical history, physical exam, and laboratory tests
- At least 18 years of age on the day of screening and have not reached their 46th birthday on the day of the first administration
- Willing to undergo HIV testing, risk reduction counseling and receive HIV test results; committed to maintaining low-risk behavior for the trial duration
- Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study
- All male and female participants of reproductive potential who are engaging in sexual activity that could lead to pregnancy must commit to use an effective method of contraception from enrollment until 9 months after the last administration
- Willing to forgo donations of blood, or any other tissues during the study following confirmation of study eligibility and, for those who test HIV-positive due to antibody-induced seropositivity, until the anti-HIV antibody titers become undetectable on HIV tests used in the community
Exclusion Criteria:
- Confirmed HIV infection
- Reported risk for HIV infection within 6 months prior to investigational product administration, as defined by: Unprotected sexual intercourse with a known HIV-infected person, a partner known to be at high risk for HIV infection and/or a casual partner (i.e. no continuing established relationship), engaged in sex work, frequent excessive daily alcohol use or frequent binge drinking or any other use of illicit drugs, history of newly-acquired syphilis, gonorrhea, non-gonococcal urethritis, HSV-2, chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B or hepatitis C, three or more sexual partners
- Any clinically significant acute or chronic medical condition that is considered progressive or in the opinion of the investigator makes the participant unsuitable for participation in the study
- Infectious disease diagnosis: Hepatitis B infection as measured by HbsAg and/or PCR, Hepatitis C infection (US: HCV RNA positive, or interferon-alpha treatment for hepatitis C infection in the past year, or interferon-alpha-free treatment for hepatitis C infection completed in the past 6 months; Africa: HCV Ab positive and/or PCR positive), active syphilis (positive RPR confirmed by TPHA)
- Receipt of blood transfusion or blood-derived products within the previous 3 months
- Participation in another clinical trial of an investigational product currently, within the previous 3 months or expected participation during this study (Concurrent participation in an observational trial not requiring blood or tissue sample collection is not an exclusion)
- Psychiatric condition that compromises safety of the participant and precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years
- Body mass index (BMI) >40
- Active tuberculosis
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 방지
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 더블
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Group 1
Single Agent, abdominal subcutaneous injection, 10:2 ratio for Ab:placebo |
300mg 0.9% Saline Buffer Solution |
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실험적: Group 2
Single agent, abdominal subcutaneous injection 10:2 ratio for Ab:placebo |
0.9% Saline Buffer Solution 300mg |
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실험적: Group 3
Single agent intravenous injection 10:2 ratio for Ab:placebo |
300mg 0.9% Saline Buffer Solution |
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실험적: Group 4
Single agent intravenous injection 10:2 ratio for Ab:placebo |
0.9% Saline Buffer Solution 300mg |
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실험적: Group 5
Combined agent intravenous injection 10:2 ratio for Ab:placebo |
0.9% Saline Buffer Solution 30mg/kg of each |
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실험적: Group 6
Subcutaneous injection combined ratio 1 with loading dose 30:3 ratio of Ab:Placebo |
0.9% Saline Buffer Solution Total ~300 mg (< 2.5 ml) combined of 3BNC117-LS-J and 101074-LS-J - Dosage ratios chosen will be those considered worthy of further investigation based on the safety and preliminary PK observed in groups 1-2 |
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실험적: Group 7
Subcutaneous injection in abdomen combined ratio 2 with loading dose 30:3 ratio of Ab:Placebo |
0.9% Saline Buffer Solution Total ~300 mg (< 2.5 ml) combined of 3BNC117-LS-J and 101074-LS-J - Dosage ratios chosen will be those considered worthy of further investigation based on the safety and preliminary PK observed in groups 1-2 |
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실험적: Group 8
Subcutaneous injection in abdomen combined ratio 3 with loading dose 30:3 ratio of Ab:Placebo |
0.9% Saline Buffer Solution Total ~300 mg (< 2.5 ml) combined of 3BNC117-LS-J and 101074-LS-J - Dosage ratios chosen will be those considered worthy of further investigation based on the safety and preliminary PK observed in groups 1-2 |
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실험적: Group 9
Subcutaneous injection in abdomen combined ratio 2 without loading dose 30:3 ratio of Ab:Placebo |
0.9% Saline Buffer Solution Total ~300 mg (< 2.5 ml) combined of 3BNC117-LS-J and 101074-LS-J - Dosage ratios chosen will be those considered worthy of further investigation based on the safety and preliminary PK observed in groups 1-2 |
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실험적: Group 10
Subcutaneous injection in arm combined ratio 2 without loading dose 30:3 ratio of Ab:Placebo |
0.9% Saline Buffer Solution Total ~300 mg (< 2.5 ml) combined of 3BNC117-LS-J and 101074-LS-J - Dosage ratios chosen will be those considered worthy of further investigation based on the safety and preliminary PK observed in groups 1-2 |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
기간 |
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1. 요청 및 치료 관련 요청하지 않은 부작용이 있는 참가자의 비율 및 기간.
기간: 92주
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92주
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연구 기간 동안 연구 제품 및 기간과 관련된 것으로 간주되는 심각한 부작용(SAE)이 있는 참가자의 비율.
기간: 92주
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92주
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참가자 특성(예: 성별, 체중 및 BMI)과 함께 여러 시점에서 각 그룹의 각 항체의 혈청 농도
기간: 92주
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92주
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SC 주입 시 3BNC117-LS-J 대 10-1074-LS-J의 비율은 정상 상태에서 각 bNAb의 유사한 수준을 유지할 것입니다.
기간: 92주
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92주
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2차 결과 측정
결과 측정 |
기간 |
|---|---|
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여러 시점에서 각 그룹의 항-3BNC117-LS-J 항체의 혈청 농도.
기간: 92주
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92주
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여러 시점에서 각 그룹의 항-10-1074-LS-J 항체의 혈청 농도.
기간: 92주
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92주
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공동 작업자 및 조사자
수사관
- 연구 의자: Marina Caskey, MD, Rockefeller University
간행물 및 유용한 링크
유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (실제)
연구 완료 (실제)
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
이 연구와 관련된 용어
기타 연구 ID 번호
- IAVI C100
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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