健常者におけるPVT401の第1相臨床試験
健康な被験者におけるPVT401のランダム化二重盲検プラセボ対照単回および反復投与後の安全性、忍容性、薬物動態、薬力学を評価する第1相ファーストインヒューマン試験
The goal of this clinical trial is to learn what happens to PVT401 when it enters the human body and how it affects the immune system. It will also provide information about the safety of PVT401 after a single dose and after multiple doses. The main questions it aims to answer are:
Will participants experience any side effects when taking PVT401? How long does it take PVT401 to leave the body after it is administered?
Healthy volunteers will participate in either the single ascending dose (SAD) or multiple ascending dose (MAD) phase.
In the SAD phase, participants will:
stay in the clinic for two nights, get one dose of PVT401 or a placebo intravenously (through a vein) on Day 1, have blood drawn periodically throughout their stay and be monitored for side effects, and return to the clinic for 3 follow up visits over the four weeks after dosing.
In the MAD phase, participants will:
stay in the clinic for one night prior to each dose of PVT401 or placebo, and get dosed twice a week for 5 weeks. They will have blood drawn periodically throughout the treatment period and be monitored for side effects, and return to the clinic for 4 follow up visits over the six months after dosing.
調査の概要
詳細な説明
SAD Phase: four cohorts are planned (n=6 per cohort; 2:1 randomization of PVT401 to placebo). This phase consists of five study visits: Screening, Treatment, and Follow-up (Day 8, Day 15, and Day 29). The Screening and Follow-up visits are outpatient; the Treatment visit includes a two-night inpatient stay from Day -1 to Day 2.
Participants will be admitted to the clinic on Day -1, the day prior to dosing. PK sampling will take place on Day 1, and the safety and tolerability of the study drug will be monitored for each participant in the clinic until Day 2 (24 hours post-dose) checkout.
The decision to advance to the subsequent SAD dose cohort will be made by a Safety Review Committee (SRC) following review of all available safety and tolerability data of participants through Day 8.
After completion of a minimum of four cohorts and with the approval of the SRC, the study will transition to the MAD phase.
MAD Phase: two cohorts are planned (n=6 per cohort; 2:1 randomization of PVT401 to placebo). This phase consists of 15 study visits: Screening: Visit 1, Treatment (Visits 2 - 11, dosing b.i.w. for 5 weeks), and Follow-up (Visits 12 - 15, up to 6 months post-dose).
All Treatment visits include a one-night inpatient stay prior to dosing; the Screening and Follow-up visits are outpatient.
The Screening visit can take place up to 42 days prior to Day 1. Participants will check in to the clinic on Day -1, the day prior to the first planned dose on Day 1. Dosing in each cohort will commence with two sentinel participants randomized such that one will receive PVT401 and the other will receive placebo (normal saline; 0.9% sodium chloride). The safety and tolerability of the study drug will be monitored for each sentinel participant through the first two doses (Week 1, Day 1 and Day 4) and will be reviewed by the Investigator prior to dosing the remainder of the participants in the cohort. Following completion of the Day 4 assessments for sentinel participants, all available safety/tolerability information will be reviewed by the Investigator prior to making the decision to dose the remaining participants in each cohort. Once safety and tolerability have been confirmed, the remaining four participants will be randomised (3:1 ratio of PVT401:placebo).
On Week 1, Day 1, all participants will remain for 8 hours after their first dose for observation and PK sampling prior to discharge. Participants will also remain for assessments and observation for a minimum of 8 hours post-dose at all other dosing visits.
The decision to advance to the next MAD dose cohort will be made by the SRC after completion of the five-week dosing cycle, following review of all available safety and tolerability data from the previous cohorts.
研究の種類
入学 (推定)
段階
- フェーズ 1
連絡先と場所
研究連絡先
- 名前：Sarah Executive Director, Clinical Operations
- 電話番号：+1 949 378 0896
- メール：sgrimberg@parvustx.com
研究場所
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Victoria
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Melbourne、Victoria、オーストラリア、3004
- 募集
- Nucleus Network Pty Ltd
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コンタクト：
- Research Coordinator
- 電話番号：61 1800 423 733
- メール：melbourne@nucleusnetwork.com
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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:
- Healthy male or female, aged between 18 and 65 years, inclusive at Screening.
- Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive.
- Carry the HLA DRB4*0101 or DRB4*0103 allele.
- Participant is medically healthy (in the opinion of the Investigator), as determined by pre-study medical history and without clinically significant (CS) abnormalities.
- Female participants must be of non-child-bearing potential, or, if of child-bearing potential, must have negative pregnancy test, agree not to become pregnant or donate ova, and must agree to use adequate contraception.
- Male participants must agree not to donate sperm and use adequate contraception.
Exclusion Criteria:
- Any active infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
- History of hypersensitivity reaction, anaphylaxis or other CS reactions or known allergy to the study drug or its ingredients including but not limited to dextran.
- History of any CS disorder which, in the opinion of the Investigator would make implementation of the protocol or interpretation of study results difficult, or that would put the participant at risk by participating in the study.
- History of surgery or hospitalisation within 4 weeks prior to Screening, or surgery planned during the study.
- Participant has donated blood or blood products or experienced significant blood loss within 2 months prior to the first dose of study drug.
- Use of any vaccinations within 4 weeks prior to the first dose of study drug.
- Laboratory results at Screening that indicate inadequate renal function, with estimated creatinine clearance of < 60 mL/min/1.73m2.
- Use of any prescription medication within 14 days prior to the first dose of study drug and/or over-the-counter medication/vitamins/supplements/herbal/ plant-derived medications within 7 days prior to the first dose of study drug.
- Concurrent enrolment in another clinical study, or participation in another clinical study within 30 days or 5 half-lives, whichever is longer, prior to Screening.
- Regular consumption of > 10 standard alcoholic drinks/week. Participant is unwilling to abstain from alcohol while confined to the study clinic.
- Positive alcohol breath test at Screening, upon admission to the clinic on Day -1.
- Positive urine drugs of abuse test at Screening, upon admission to the clinic on Day -1.
- Participant is a heavy smoker, define as more than 2 cigarettes per day or 10 per week.
- Participant is unwilling to abstain from smoking while confined to the study clinic.
- Participant is breastfeeding/lactating or pregnant, or planning to breastfeed or become pregnant during the study.
- Positive Hepatitis B surface antigen (HBsAg), Hepatitis C (HepC) virus antibody, or human immunodeficiency (HIV) antibody tests.
- Positive for tuberculosis (TB) disease or latent TB infection.
- Ingestion of poppy seed-containing foods or beverages within 48 hours prior to first dose of study drug.
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 |
|---|---|
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実験的：single dose PVT401
PVT401 will be administered as a single intravenous dose to healthy volunteers. There are a minimum of four cohorts planned, with the dose escalating in each subsequent cohort. |
Parvus pMHC nanomedicines are being developed for the treatment of autoimmune diseases. They consist of an iron oxide core surrounded by dextran that has been linked to multiple copies of a major histocompatibility complex Class II molecule and peptide. The peptide representing a disease-associated autoantigen and its paired MHC II molecule are specific to each autoimmune disease, and will be recognized by the T-cell antigen receptor. PVT401 is a nanomedicine that will be used to target effector T-cells in patients with inflammatory bowel disease (IBD), converting them to Type 1 regulatory cells. IV delivery in nonclinical models of IBD induced immune tolerance and attenuation of disease pathology without impairing normal immunity to vaccines or viral and bacterial infections. PVT401 will be administered intravenously to healthy volunteers, first as a single dose and then as a multiple dose treatment regimen.
他の名前：
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プラセボコンパレーター：single dose, normal saline
Participants receiving placebo will be administered a single intravenous dose of normal saline at an equivalent volume to a single IV PVT401 dose (mg/kg). |
All cohorts will be administered either PVT401 or placebo in a ratio of 2:1 PVT401:placebo. Participants receiving placebo will be administered an equivalent volume of normal saline as either a single IV dose or as a multiple dose treatment regimen.
他の名前：
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実験的：multiple doses, PVT401
Following completion of single-dose cohorts, PVT401 will be administered as a multiple intravenous dose treatment regimen to healthy volunteers. There are two cohorts planned, with the dose escalating in each subsequent cohort. |
Parvus pMHC nanomedicines are being developed for the treatment of autoimmune diseases. They consist of an iron oxide core surrounded by dextran that has been linked to multiple copies of a major histocompatibility complex Class II molecule and peptide. The peptide representing a disease-associated autoantigen and its paired MHC II molecule are specific to each autoimmune disease, and will be recognized by the T-cell antigen receptor. PVT401 is a nanomedicine that will be used to target effector T-cells in patients with inflammatory bowel disease (IBD), converting them to Type 1 regulatory cells. IV delivery in nonclinical models of IBD induced immune tolerance and attenuation of disease pathology without impairing normal immunity to vaccines or viral and bacterial infections. PVT401 will be administered intravenously to healthy volunteers, first as a single dose and then as a multiple dose treatment regimen.
他の名前：
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プラセボコンパレーター：multiple doses, normal saline
Participants receiving placebo will be administered multiple intravenous doses of normal saline at an equivalent volume to the IV PVT401 dose (mg/kg). |
All cohorts will be administered either PVT401 or placebo in a ratio of 2:1 PVT401:placebo. Participants receiving placebo will be administered an equivalent volume of normal saline as either a single IV dose or as a multiple dose treatment regimen.
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 |
|---|---|---|
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To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: adverse and serious adverse events
時間枠：From enrollment through 4-weeks post last dose of study drug
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Safety endpoints include incidence, severity, and relationship of adverse events (AEs) and serious adverse events (SAEs) (including withdrawals due to AEs) |
From enrollment through 4-weeks post last dose of study drug
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To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: vital signs (temperature)
時間枠：From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
Safety endpoints include change from baseline in vital signs (temperature measured in degrees Celsius) |
From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
|
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: vital signs (heart rate)
時間枠：From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
Safety endpoints include change from baseline in vital signs (heart rate measured in beats per minute) |
From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
|
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: vital signs (blood pressure)
時間枠：From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
Safety endpoints include change from baseline in vital signs (blood pressure measured in mmHg) |
From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
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To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: clinical laboratory parameters (hematology panel)
時間枠：From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
Safety endpoints include change from baseline in clinical laboratory parameters (hematology) |
From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
|
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants.: clinical laboratory parameters (serum chemistry panel)
時間枠：From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
Safety endpoints include change from baseline in clinical laboratory parameters (serum chemistry including liver function tests). |
From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
|
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: clinical laboratory parameters (coagulation panel)
時間枠：From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
Safety endpoints include change from baseline in clinical laboratory parameters (coagulation parameters). |
From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
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To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: clinical laboratory parameters (urinalysis)
時間枠：From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
Safety endpoints include change from baseline in clinical laboratory parameters (urinalysis). |
From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
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To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: clinical laboratory parameters (serum iron panel)
時間枠：From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
Safety endpoints include change from baseline in clinical laboratory parameters (serum iron panel) |
From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
|
To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: ECG (PR interval)
時間枠：From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
Safety endpoints include change from baseline in electrocardiogram (ECG) parameters: PR Interval (milliseconds) |
From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
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To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: ECG (QRS duration)
時間枠：From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
Safety endpoints include change from baseline in electrocardiogram (ECG) parameters: QRS Duration (milliseconds) |
From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
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To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: ECG (QT interval)
時間枠：From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
Safety endpoints include change from baseline in electrocardiogram (ECG) parameters: QT Interval (milliseconds) |
From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
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To evaluate the safety and tolerability of a single and multiple IV doses of PVT401 in healthy participants: ECG (QTcF)
時間枠：From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
Safety endpoints include change from baseline in electrocardiogram (ECG) parameters: QTcF (milliseconds) |
From enrollment through 4 weeks after dosing (single dose cohorts) or 6 months after the final dose (multiple dose cohorts)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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To measure the PK of PVT401 in plasma following single and multiple IV doses in healthy volunteers.
時間枠：Single Dose Cohorts: multiple timepoints pre-dose to 24 hours post-dose Multiple Dose Cohorts: *First and Last Dose: multiple timepoints from pre-dose to 4 hours post-dose
|
PK parameters to be evaluated include area under the concentration-time curve from 0 to time of last quantifiable concentration (AUClast) |
Single Dose Cohorts: multiple timepoints pre-dose to 24 hours post-dose Multiple Dose Cohorts: *First and Last Dose: multiple timepoints from pre-dose to 4 hours post-dose
|
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To measure the PK of PVT401 in plasma following single and multiple IV doses in healthy volunteers.
時間枠：Single Dose Cohorts: multiple timepoints pre-dose to 24 hours post-dose Multiple Dose Cohorts: *First and Last Dose: multiple timepoints from pre-dose to 4 hours post-dose
|
PK parameters to be evaluated include area under the concentration-time curve from 0 to infinity (AUCinf) |
Single Dose Cohorts: multiple timepoints pre-dose to 24 hours post-dose Multiple Dose Cohorts: *First and Last Dose: multiple timepoints from pre-dose to 4 hours post-dose
|
|
To measure the PK of PVT401 in plasma following single and multiple IV doses in healthy volunteers.
時間枠：Single Dose Cohorts: multiple timepoints pre-dose to 24 hours post-dose Multiple Dose Cohorts: *First and Last Dose: multiple timepoints from pre-dose to 4 hours post-dose
|
PK parameters to be evaluated include maximum concentrations (Cmax); |
Single Dose Cohorts: multiple timepoints pre-dose to 24 hours post-dose Multiple Dose Cohorts: *First and Last Dose: multiple timepoints from pre-dose to 4 hours post-dose
|
|
To measure the PK of PVT401 in plasma following single and multiple IV doses in healthy volunteers.
時間枠：Single Dose Cohorts: multiple timepoints pre-dose to 24 hours post-dose Multiple Dose Cohorts: *First and Last Dose: multiple timepoints from pre-dose to 4 hours post-dose
|
PK parameters to be evaluated include time at which the maximum concentration is observed (tmax); |
Single Dose Cohorts: multiple timepoints pre-dose to 24 hours post-dose Multiple Dose Cohorts: *First and Last Dose: multiple timepoints from pre-dose to 4 hours post-dose
|
|
To measure the PK of PVT401 in plasma following single and multiple IV doses in healthy volunteers.
時間枠：Single Dose Cohorts: multiple timepoints pre-dose to 24 hours post-dose Multiple Dose Cohorts: *First and Last Dose: multiple timepoints from pre-dose to 4 hours post-dose
|
PK parameters to be evaluated include apparent terminal elimination half-life (t1/2) |
Single Dose Cohorts: multiple timepoints pre-dose to 24 hours post-dose Multiple Dose Cohorts: *First and Last Dose: multiple timepoints from pre-dose to 4 hours post-dose
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
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
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