- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT01704781
Vacc-4x + Lenalidomide vs. Vacc-4x +Placebo in HIV-1-infected Subjects on Antiretroviral Therapy (ART) (IMID)
A Double-blind Placebo Controlled Immunogenicity Study of Vacc-4x + Lenalidomide Versus Vacc-4x With an Initial Open-label Dose Escalation Assessment of Lenalidomide in HIV-1-infected Subjects on Antiretroviral Therapy (ART).
연구 개요
상세 설명
Human immunodeficiency virus (HIV) infects the CD4 subset of T-cells that are critical for initiating immune responses to infection. The level of CD4 cells in the blood is a marker of a patient's immunological status. The number of CD4 cells decreases in the course of the HIV infection and results in a reduced immunological response and eventually immune deficiency.
Vacc-4x is one of the few peptide-based therapeutic vaccines tested, and consists of four, slightly modified HIV Gag p24 consensus peptides. Vacc-4x was first tested by intradermal injections using GM-CSF as adjuvant. A recent multinational placebo-controlled study found improvement of vaccine-specific T cell immunity and decrease in viral loads (presented at the AIDS vaccine 2011 conference, Bangkok).
Lenalidomide (CC-5013) is a substance in the class of immunomodulatory agents. The lenalidomide mechanism of action includes anti-neoplastic, pro-erythropoietic, and immunomodulatory properties. Lenalidomide inhibits proliferation of certain hematopoietic tumor cells, enhances T cell- and Natural Killer (NK) cell-mediated immunity and increases the number of NK T cells.
The anti-HIV p24 immune response resulting from Vacc-4x immunization could in combination with ART potentially improve immune reconstitution in patients who have not fully regained a healthy CD4 level (> 600 x106/L). Adding the immunomodulatory agent Lenalidomide (CC-5013) to Vacc-4x immunization could enhance the immune response to Vacc-4x and further strengthen immune reconstitution.
연구 유형
등록 (실제)
단계
- 2 단계
- 1단계
연락처 및 위치
연구 장소
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Berlin, 독일, 12157
- EIPMED - Gesellschaft fűr epidemiologische und klinische Forschung in der Medizin mbH Rubensstrasse 125
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Berlin, 독일, 13353
- Charite Campus, Virchow-Klinikum Medizinische Klinik mit Schwerpunkt Infektiologie Station 59 (Suedring 11) Augustenburger Platz 1
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Hamburg, 독일, 20246
- University Medical Center Hamburg-Eppendorf
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Köln, 독일, 50937
- Klinik I für Innere Medizin Klinikum Der Universität zu Köln
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Men, age ≥ 18 and ≤ 55 years at the time of screening.
- Women, age ≥ 50 and ≤ 55 years at the time of screening, who are not of childbearing potential (see Exclusion criteria, point 9). Childbearing status must be documented.
- Clinically stable on ART for the last 18 months (changes in therapy are allowed as long as the viral load is stable).
- Well controlled with no treatment failure due to ART resistance in the past
- Screening plasma viral load (HIV-1 RNA) less than 50 copies/mL for the last six months. If screening value is between 50-500 copies/mL rescreening is allowed. Single blips (up to 500 copies/mL) are allowed.
- Screening CD4 cell count ≥ 200x10^6 cells/L and ≤500x10^6 cells/L. (Rescreening is allowed)
- Laboratory test results within these ranges: Absolute neutrophil count (ANC) >1.0x10^9 /L, Platelet count >75x10^9 /L and eGRF (MDRD) >60 mL/min
- Signed informed consent
- Willingness to adhere to Global Pregnancy Prevention Risk Management Plan Lenalidomide
Exclusion Criteria:
- Reported pre-study AIDS-defining illness within the previous year
- Malignant disease.
- On chronic treatment with immunosuppressive therapy.
- Autoimmune disorders, present or in the past if there is an increased risk of disease exacerbation.
- Unacceptable values of the hematologic and clinical chemistry parameters (including those associated with hemophilia), as judged by the Investigator or the Sponsor (or designee), including creatinine values >1.5x upper limit of normal (ULN), and AST (SGOT), ALT (SGPT), and alkaline phosphatase values >2.5x ULN.
- Concurrent chronic active infection such as viral hepatitis B or C or tuberculosis.
- Previous thromboembolic events or patient is currently immobilized
- Sexually active subjects who do not adhere to Global Pregnancy Prevention Risk Management Plan Lenalidomide
- Current participation in other clinical therapeutic studies.
- Females of childbearing potential will be excluded from this trial. A female of childbearing potential (FCBP) is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e. has had menses at any time in the preceding 24 consecutive months).
- The development of erythema nodosum if characterized by a desquamating rash while previously
- Incapability of compliance to the treatment protocol, in the opinion of the Investigator.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 지지 요법
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Part A: lenalidomide dose escalation
All patient receive intradermal Vacc-4x (1.2 mg) given with Leukine® (rhu-GM-CSF) (0.06 mg) and oral lenalidomide in a dose escalation (3+3) design. Dose level -1: 2.5 mg Lenalidomide (CC-5013) in the event Dose level 1 is non tolerated dose (NTD) Dose level 1(start): 5 mg Lenalidomide (CC-5013) Dose level 2: 10 mg Lenalidomide (CC-5013) Dose level 3: 25 mg Lenalidomide (CC-5013) |
In Part A a dose escalation design is used (2,5; 5; 10; 25 mg).
Part B will use the dose confirmed by Part A
다른 이름들:
Vacc-4x is a peptide-based HIV immunotherapy administered intradermally.
Vacc-4x peptides are reconstituted in sterile water.
다른 이름들:
Granulocyte macrophage colony stimulating factor as a local adjuvant
다른 이름들:
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실험적: Part B: lenalidomide
Intradermal Vacc-4x (1.2 mg) given with Leukine® (rhu-GM-CSF) (0.06 mg) and oral lenalidomide for 6 immunizations (visit 2, 3, 4, 5, 6 and 7) & lenalidomide (dose determined in Part A) two days prior to and at the day of immunization.
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In Part A a dose escalation design is used (2,5; 5; 10; 25 mg).
Part B will use the dose confirmed by Part A
다른 이름들:
Vacc-4x is a peptide-based HIV immunotherapy administered intradermally.
Vacc-4x peptides are reconstituted in sterile water.
다른 이름들:
Granulocyte macrophage colony stimulating factor as a local adjuvant
다른 이름들:
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위약 비교기: Part B: lenalidomide placebo
Intradermal Vacc-4x (1.2 mg) given with Leukine® (rhu-GM-CSF) (0.06 mg) and oral lenalidomide for 6 immunizations (visit 2, 3, 4, 5, 6 and 7) & lenalidomide placebo two days prior to and at the day of immunization.
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Vacc-4x is a peptide-based HIV immunotherapy administered intradermally.
Vacc-4x peptides are reconstituted in sterile water.
다른 이름들:
Granulocyte macrophage colony stimulating factor as a local adjuvant
다른 이름들:
Capsules are identical to the active Lenalidomide capsules used.
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Part A: To Establish Highest Tolerated Dose of Lenalidomide, Dose-Limiting Toxicity
기간: 31 days
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Number of participants in each of the three groups that experienced any dose-limiting toxicity.
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31 days
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Part A: To Establish Highest Tolerated Dose of Lenalidomide, CD4 Counts Over Time
기간: 31 days
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31 days
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Part B: Change in CD4 Count
기간: Week 26
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Change in CD4 count from baseline to Week 26.
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Week 26
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Part B: Change in CD8 Count
기간: 26 weeks
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Change in CD8 count from baseline to week 26.
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26 weeks
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Part B: Evaluate the Effect on HIV Viral Load
기간: 26 weeks
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Results BLQ (<20 HIV copies/mL) have been replaced with BLQ/2 = 10 HIV copies/mL while 'not detected' results have been replaced with 0 HIV copies/mL.
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26 weeks
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Part B: Incidents of Delayed-type Hypersensitivity
기간: 26 weeks
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Delayed-type hypersensitivity measured by induration and erythema.
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26 weeks
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Part A and B: Safety and Tolerability
기간: Part A: 31 days and Part B: 26 weeks
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Part A: 31 days and Part B: 26 weeks
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공동 작업자 및 조사자
스폰서
수사관
- 연구 책임자: Kim Krogsgaard, Bionor Pharma ASA, Kronprinsesse Märthas Plass 1, P.O. Box 1477 Vika, NO-0116 Oslo, Norway
간행물 및 유용한 링크
일반 간행물
- Asjo B, Stavang H, Sorensen B, Baksaas I, Nyhus J, Langeland N. Phase I trial of a therapeutic HIV type 1 vaccine, Vacc-4x, in HIV type 1-infected individuals with or without antiretroviral therapy. AIDS Res Hum Retroviruses. 2002 Dec 10;18(18):1357-65. doi: 10.1089/088922202320935438.
- Kran AM, Sorensen B, Nyhus J, Sommerfelt MA, Baksaas I, Bruun JN, Kvale D. HLA- and dose-dependent immunogenicity of a peptide-based HIV-1 immunotherapy candidate (Vacc-4x). AIDS. 2004 Sep 24;18(14):1875-83. doi: 10.1097/00002030-200409240-00003.
- Kvale D, Kran AM, Sommerfelt MA, Nyhus J, Baksaas I, Bruun JN, Sorensen B. Divergent in vitro and in vivo correlates of HIV-specific T-cell responses during onset of HIV viraemia. AIDS. 2005 Mar 24;19(6):563-7. doi: 10.1097/01.aids.0000163932.76531.c6.
- Sommerfelt MA, Nyhus J, Sorensen B. Novel peptide-based HIV-1 immunotherapy. Expert Opin Biol Ther. 2004 Mar;4(3):349-61. doi: 10.1517/14712598.4.3.349.
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
기타 연구 ID 번호
- CT-BI Vacc-4x/IMiD-2010/1
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
HIV-1 감염에 대한 임상 시험
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Janssen Pharmaceutica N.V., Belgium완전한
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Merck Sharp & Dohme LLC완전한
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Janssen Research & Development, LLC완전한
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Janssen-Cilag Ltd.완전한
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Fundacion para la Investigacion Biomedica del Hospital...Pfizer완전한
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PfizerViiV Healthcare완전한
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Gilead Sciences완전한HIV-1오스트리아, 독일, 이탈리아, 스페인
Lenalidomide에 대한 임상 시험
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Johns Hopkins All Children's Hospital종료됨
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Mingzhi Zhang알려지지 않은
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Assistance Publique - Hôpitaux de Paris모집하지 않고 적극적으로
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The First Affiliated Hospital of Soochow UniversityThe First Affiliated Hospital with Nanjing Medical University; Jiangsu Province Hospital... 그리고 다른 협력자들모병
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Celgene Corporation완전한새로 진단된 다발성 골수종스페인, 네덜란드, 오스트리아, 호주, 이탈리아, 러시아 연방, 영국, 이스라엘, 벨기에, 그리스, 독일, 폴란드, 칠면조, 프랑스, 덴마크, 체코 공화국, 벨라루스, 그루지야, 아일랜드, 스웨덴, 스위스, 우크라이나
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University of LeedsMerck Sharp & Dohme LLC; Celgene; Amgen알려지지 않은