成人参加者におけるプラセボと比較した VXX-401 の安全性、忍容性、免疫原性、および薬力学を調査する研究
健康な成人におけるVXX-401の安全性、忍容性、免疫原性、および薬力学を評価するためのフェーズ1、ファーストインヒューマン、無作為化、二重盲検、プラセボ対照、用量漸増試験
This first-in-human (FIH) study of VXX-401, an anti-PCSK9 peptide-based immunotherapeutic candidate, is designed to assess the safety, tolerability, immunogenicity, and pharmacodynamics (PD) of VXX-401 and to determine an optimal dose regimen for LDL-C lowering in subsequent clinical trials.
調査の概要
詳細な説明
This is multisite, multidose regimen, phase 1, first-in-human study of VXX-401, a synthetic peptide-based active immunotherapy candidate for preventing and treating hypercholesterolemia. The study will include Screening, Treatment, and Follow-up Periods. This study will enroll participants who are naïve to statin use. Each cohort from A to D is planned to randomize approximately 12 participants to receive doses of VXX-401 or placebo in a 3:1 ratio. Cohorts E and F will dose approximately 8 participants in each cohort to receive doses of VXX-401. No participants will be administered placebo in Cohorts E and F. It is planned to test up to 6 dose regimens of VXX-401, administered by IM injection into the deltoid muscle (and additionally in the thigh for the first dose in Cohorts E-F.). All eligible participants will receive a priming regimen at Week 0 (Baseline, Day 1), Week 4, and Week 12, in Cohorts A, C, E and F, and additionally at Week 8 in Cohorts B and D. The last dose administration will be at Week 12.
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
-
-
New South Wales
-
Brookvale、New South Wales、オーストラリア
- Northern Beaches Clinical Research
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Miranda、New South Wales、オーストラリア
- Sutherland Shire Clinical Research
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Sydney、New South Wales、オーストラリア
- Emeritus Research
-
-
Queensland
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Morayfield、Queensland、オーストラリア
- University of the Sunshine Coast (USC)
-
-
Victoria
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Melbourne、Victoria、オーストラリア
- Emeritus Research
-
-
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:
- Male or female participants aged 18 to 75 years old, inclusive, at time of informed consent.
- LDL-C level = 2.59 mmol/L - 4.89mmol/L
- Body mass index between 18 and 35 kg/m2, inclusive at Screening, and with a minimum weight of 50 kg.
- Male participants and their partners of childbearing potential must commit to the use of highly effective contraceptives for the study duration and for at least 12 weeks after the last dose. Men must refrain from donating sperm during this same period.
- Female participants must be of nonchildbearing potential, or, for women of childbearing potential, must be willing to practice at least one form of highly effective contraception throughout the duration of the study and for at least 24 weeks following the last dose. Female participants must refrain from donating reproductive tissue during this same period.
Exclusion Criteria:
- Subjects considered high risk or very high risk for ASCVD and requiring immediate treatment with LLT according to the clinical judgement of the investigator.
- History of confirmed anergy (i.e., not able to mount an immunological response) or history of immunization failure in the 5 years prior to the Screening Visit.
- Presence of fever >38°C or other signs or symptoms of acute disease within 1 week before the Screening and/or Visit 1; Screening and/or Visit 1 may be rescheduled at the discretion of the Investigator but must occur within the 4-week window.
- Known disturbance of coagulation or medication (see prohibited medications criterion below); bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture.
- Triglycerides > 5.65 mmol/L
- Has a history of clinically significant medical disorder or psychiatric conditions, which in the opinion of the investigator may compromise the participant's safety and ability to comply with study procedures or abide by study restrictions.
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：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：VXX-401 Cohort A
VXX-401 100mcg administered by intramuscular (IM) injection at Week 0, Week 4, and Week 12 |
A synthetic PCSK9 peptide-based immunotherapy |
|
実験的：VXX-401 Cohort B
VXX-401 100mcg administered by intramuscular (IM) injection at Week 0, Week 4, Week 8 and Week 12 |
A synthetic PCSK9 peptide-based immunotherapy |
|
実験的：VXX-401 Cohort C
VXX-401 300mcg administered by intramuscular (IM) injection at Week 0, Week 4, and Week 12 |
A synthetic PCSK9 peptide-based immunotherapy |
|
実験的：VXX-401 Cohort D
VXX-401 300mcg administered by intramuscular (IM) injection at Week 0, Week 4, Week 8 and Week 12 |
A synthetic PCSK9 peptide-based immunotherapy |
|
プラセボコンパレーター：Placebo Cohort A and C
Placebo administered by intramuscular (IM) injection at Week 0, Week 4, and Week 12 |
Normal saline |
|
プラセボコンパレーター：Placebo Cohort B and D
Placebo administered by intramuscular (IM) injection at Week 0, Week 4, Week 8 and Week 12 |
Normal saline |
|
実験的：VXX-401 Cohort E
VXX-401 900mcg administered by intramuscular (IM) injection at Week 0. VXX-401 100 mcg administered by intramuscular (IM) injection at Week 4 and Week 12. |
A synthetic PCSK9 peptide-based immunotherapy |
|
実験的：VXX-401 Cohort F
VXX-401 900mcg administered by intramuscular (IM) injection at Week 0. VXX-401 300 mcg administered by intramuscular (IM) injection at Week 4 and Week 12. |
A synthetic PCSK9 peptide-based immunotherapy |
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 |
|---|---|---|
|
Frequency of adverse events
時間枠：30 weeks
|
Safety and tolerability: rates of adverse events (AEs), medically attended adverse events (MAAEs), local (injection site) and systemic (generalized) reactions (i.e., reactogenicity), clinical laboratory assessments (e.g., chemistry, hematology, urinalysis, lipid profile), serum cytokine release, vital signs, physical examinations, and electrocardiograms (ECGs) through the end of the study. |
30 weeks
|
|
Immunogenicity
時間枠：Baseline to Week 16, 20, 24, and 30
|
Immunogenicity will be measured by serum anti-PCSK9 antibody titers |
Baseline to Week 16, 20, 24, and 30
|
|
Immunogenicity
時間枠：Baseline to Week 16, 20, 24, and 30
|
Seroconversion two-fold and four-fold from baseline |
Baseline to Week 16, 20, 24, and 30
|
|
Determine optimal VXX-401 dose regimen
時間枠：Baseline to Week 16, 20, 24, and 30
|
Measured by serum anti-PCSK9 antibody titers |
Baseline to Week 16, 20, 24, and 30
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Evaluation of low-density lipoprotein-cholesterol (LDL-C) reduction
時間枠：Baseline to Week 16, 20, 24, and 30
|
Percent change from baseline in serum LDL-C concentration |
Baseline to Week 16, 20, 24, and 30
|
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：Sasha Rumyantsev、Vaxxinity, Inc.
研究記録日
主要日程の研究
研究開始 (実際)
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 (実際)
学習記録の更新
投稿された最後の更新 (実際)
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。