Immunotherapy With Vacc-C5 With Adjuvant GM-CSF or Alhydrogel in HIV-1-infected Subjects on ART
Immunotherapy of HIV-infected Patients An Open, Dose-escalating Assessment of Vacc-C5 With Either GM-CSF or Alhydrogel as Adjuvant in HIV-1-infected Subjects on Antiretroviral Therapy (ART)
Background:
Despite the introduction of highly effective antiretroviral therapy (ART) regimes, which control the HIV infection and results in increases in CD4 cell counts and an undetectable viral load, many patients suffer from increased morbidity. There is evidence that presence of antibodies against the C5 region of gp120 strongly correlates with slower disease progression, and that loss of antibody responses to this region are associated with progression.
Investigational product:
Vacc-C5 is a single heterodimeric peptide-based HIV therapeutic vaccine corresponding to the C5 region on gp120 and the external domain of gp41. The vaccine is intended to create a non-neutralizing antibody against C5 region.
Study objectives:
- To evaluate safety of the vaccination regimens
- To evaluate C5-specific humoral immune responses (antibodies), T cell responses, T cell activation markers and other immune markers.
調査の概要
詳細な説明
Background:
Despite the introduction of highly effective antiretroviral therapy (ART) regimes, which control the HIV infection and results in increases in CD4 cell counts and an undetectable viral load, many patients suffer from increased morbidity. There is evidence that presence of antibodies against the C5 region of gp120 strongly correlates with slower disease progression, and that loss of antibody responses to this region are associated with progression.
Investigational product:
Vacc-C5 is a single heterodimeric peptide-based HIV therapeutic vaccine corresponding to the C5 region on gp120 and the external domain of gp41. The rationale behind the Vacc-C5 is the finding that long-term non-progressors (LTNP) subjects have more antibodies towards the C5 part of gp120 than HIV infected subjects with a more rapid disease progression.
The primary objective of Vacc-C5 immunotherapy is to induce a humoral immune response. The vaccine is intended to create a non-neutralizing antibody against the C5 region and to thereby mimic a natural process in HIV-infected long-term non-progressors (LTNP) subjects.
Use of adjuvant:
Peptide vaccines are poorly immunogenic by themselves. To induce measurable levels of T helper cell type 1 (Th1) or type 2 (Th2) immune responses against these peptides, an adjuvant is often required.
Two different adjuvants are to be used in this study:
- GM-CSF which facilitates dendritic cell maturation and migration to the lymph nodes for antigen presentation. The regimen when using this adjuvant is intradermal administration.
- Aluminum-containing adjuvants is well known. They have been administered to human beings and animals in millions of doses of vaccines. This type of vaccine is usually administered intramuscularly or subcutaneously. In this study intramuscular administration will be used.
Primary objective:
It is to evaluate the safety of Vacc-C5 at three different dose levels given intradermally with GM-CSF as adjuvant or given intramuscularly with Alhydrogel as adjuvant.
Secondary objectives:
- To evaluate C5-specific humoral immune responses (antibodies).
- To evaluate the C5-specific T cell responses by ELISPOT and T cell proliferation.
- To evaluate T cell activation markers (e.g. CD38, HLA-DR) and other immune markers.
Study design:
The study is an open, dose-escalating, single centre study in HIV-positive subjects on treatment (ART). Two different vaccine regimens will be tested:
- Arm A: Vacc-C5 with GM-CSF as adjuvant administered intradermally.
- Arm B: Vacc-C5 with Alhydrogel as adjuvant administered intramuscularly.
Three dose levels of Vacc-C5 (100, 300 and 900 microgram will be tested for each of the two vaccination regimen. A dose escalation design (3+3) will be used, and if no dose limiting toxicity (DLT) is detected 18 subjects will be included in each arm.
Subjects who have been HIV-positive and stable on ART for the last 6 months with CD4 cell counts ≥400x 10 6 /L and who meet the other inclusion and exclusion criteria will be eligible for the study. The duration of the study is 26 weeks plus a screening period of up to 12 weeks.
During the Treatment Period, all subjects will remain on their ART and receive three immunizations; at Weeks 1, 2 and 4, with Vacc C5 including either GM-CSF or Alhydrogel as adjuvant.
The study is sequential, meaning that the first three subjects in each arm receive the lowest dose (three subjects) 100 µg Vacc-C5. If no dose limiting toxicity has been detected after week 4 vaccination, three more subjects will be added and the next dose level will be started.
研究の種類
入学 (実際)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究場所
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Oslo、ノルウェー、0450
- Oslo University Hospital, Ullevål
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Age between18 years and 55 years, both genders.
- HIV positive at least one year.
- Clinically stable on ART for the last 6 months (changes in therapy is allowed as long as the viral load is stable).
- Documented viral load (HIV-1 RNA) less than 50 copies/mL for the last six months. Single blips (up to 500 copies/mL) are allowed.
- Documented pre-study CD4 cell count ≥ 400x106/L for at least six months (if below at screening, a re-analysis is allowed).
- Nadir (lowest ever) CD4 cell count ≥ 200x106/L (nadir below 200x106/L requires two consecutive analyses).
- Signed informed consent.
Exclusion Criteria:
- Reported pre-study AIDS-defining illness within the previous year
- Malignant disease.
- On chronic treatment with immunosuppressive therapy.
- Unacceptable values of the hematologic and clinical chemistry parameters, as judged by the Principle Investigator (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.
- Pregnant or breastfeeding women.
- Women of childbearing potential not using reliable and adequate contraceptive methods (defined as: use of oral, implanted, injectable, mechanical or barrier products for the prevention of pregnancy; practicing abstinence; sterile) during the study, or sexually active male subjects with partners of childbearing potential unwilling to practice effective contraception during the study.
- Current participation in other clinical therapeutic studies.
- Incapability of compliance to the treatment protocol, in the opinion of the Investigator.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:非ランダム化
- 介入モデル:並列代入
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
---|---|
実験的:Arm 1= Arm A: Vacc-C5 /GM-CSF.
Arm 1=Arm A: Vacc-C5 with GM-CSF as adjuvant administered intradermally.
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Arm 1=Arm A: Vacc-C5 with GM-CSF as adjuvant administered intradermally.
他の名前:
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実験的:Arm 2=Arm B: Vacc-C5/Alhydrogel
Arm 2=Arm B: Vacc-C5 with Alhydrogel as adjuvant administered intramuscularly.
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Arm 2=Arm B: Vacc-C5 with Alhydrogel as adjuvant administered intramuscularly.
他の名前:
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Safety measured as change of AE records, clinical chemistry (incl. CD4, CD8, HIV-1 RNA)and hematology laboratory elevations
時間枠:From screening and week 1 to weeks 2, 4, 6, 12, 13, 15, 21, 22 and 26
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From screening and week 1 to weeks 2, 4, 6, 12, 13, 15, 21, 22 and 26
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Change in Humoral and T cell responses
時間枠:From screening and week 1 to weeks 4, 6, 12, 13, 15, 21, 22 and 26
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From screening and week 1 to weeks 4, 6, 12, 13, 15, 21, 22 and 26
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協力者と研究者
スポンサー
捜査官
- スタディディレクター:Vidar Wendel-Hansen, MD PhD、Bionor Pharma AS
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
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