A Phase 1 Single-blind, Placebo-controlled, Dose Escalation Study to Evaluate the Safety of AD-NP1, a Humanized Monoclonal Antibody Targeting Human ENPP1
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Safety and tolerability of escalating doses of a single IV dose of AD-NP1
研究概览
简要总结
This is a Phase 1 single-blind, placebo-controlled, dose-escalation study designed to evaluate the safety of AD-NP1, a humanized monoclonal antibody targeting human ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1). The study aims to assess the maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of AD-NP1 in healthy volunteers. Participants will be randomized to receive either AD-NP1 or placebo, with safety and efficacy monitored in accordance with Good Clinical Practice (GCP) guidelines. The study also seeks to explore changes in health-related quality of life (HRQOL) during the trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Body weight ≤ 90kg
- •Ability to understand and the willingness to sign a written informed consent document
- •Study subject must have read, understood, and provided written informed consent and HIPAA authorization after the nature of the study has been fully explained
- •Be in general good health without history of any of the conditions listed in
排除标准
- •No use of any tobacco products for at least 6 months
- •Woman/women of childbearing potential (WOCBP) must agree not to become pregnant from the time of study enrollment until at least 6 months after the completion of the monoclonal antibody infusion. If a WOCBP is sexually active and has no history of hysterectomy or tubal ligation, she must agree to use hormonal or barrier birth control with spermicidal gel
- •Sexually active male subjects must use a barrier method of contraception during the study
- •Screening laboratory values must meet the following criteria:
- •WBC (>3,000 - <11,000/mm^3)
- •Platelets (>100,000/mm^3)
- •Hemoglobin (>10.5 gm/dl)
- •Creatinine (<1.1 x upper limit of normal [ULN])
- •BUN (<1.25 x ULN)
- •AST (<1.1 x ULN)
- •ALT (<1.1 x ULN)
- •Alkaline Phosphatase (<1.1 x ULN)
- •Bilirubin (<1.1 x ULN)
- •Glucose-non-fasting (> 60 mg/dl and < 115 mg/dl)
- •Human immunodeficiency virus (HIV)-infected individuals on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial
- •For subjects with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- •Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured. For individuals with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
- •Exclusion Criteria:
- •Previous exposure to humanized or human monoclonal antibodies whether FDA approved or investigational
- •Weight > 90 kg
- •History of any of the following illnesses or conditions:
- •a. Respiratory condition (such as asthma requiring daily medication)
- •b. Clinically immunocompromised due to any primary immune or autoimmune deficiency, as a result of chronic disease, cancer or medication used to treat these diseases
- •c. Blood dyscrasias
- •d. Psychiatric disorder that precludes compliance with the clinical protocol
- •e. Hepatitis
- •Any chronic condition requiring daily prescription or over-the-counter medicine except for vitamins and birth control products
- •History of drug or alcohol abuse within previous 12 months or a positive urine toxicology screen within 24 hours of initial screening
- •History of a previous severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis
- •Physical finding on examination considered clinically significant such as heart murmur (other than functional), hepatosplenomegaly, lymphadenopathy, or focal neurological deficit
- •Urinalysis positive for > trace protein, >5 RBC/HPF or >5 WBC/HPF
- •Positive serology for HIV antibody, HCV antibody or Hepatitis B surface antigen
- •Positive serum pregnancy test during screening or positive urine pregnancy test within 24 hours of monoclonal antibody administration, or an unwillingness to undergo pregnancy testing
- •Currently breast-feeding
- •Receipt of an FDA approved vaccine or any investigational study agent within previous 30 days
- •Any other condition that in the opinion of the investigator would jeopardize the safety or rights of the subject participating in the study
研究组 & 干预措施
Cohort 1 - Placebo
Subjects receive a single intravenous dose of placebo matched in volume to the 30 mg/kg dose of AD-NP1
干预措施: Placebo (Drug)
Cohort 1 - AD-NP1 (30mg/kg)
Subjects receive a single intravenous dose of AD-NP1 at 30 mg/kg
干预措施: AD-NP1 (Drug)
Cohort 2 - AD-NP1 (40 mg/kg)
Subjects receive a single intravenous dose of AD-NP1 at 40 mg/kg
干预措施: AD-NP1 (Drug)
Cohort 2 - Placebo
Subjects receive a single intravenous dose of placebo matched in volume to the 40 mg/kg dose of AD-NP1
干预措施: Placebo (Drug)
Cohort 3 - AD-NP1 (60 mg/kg)
Subjects receive a single intravenous dose of AD-NP1 at 60 mg/kg
干预措施: AD-NP1 (Drug)
Cohort 3 - Placebo
Subjects receive a single intravenous dose of placebo matched in volume to the 60 mg/kg dose of AD-NP1
干预措施: Placebo (Drug)
Cohort 4 - AD-NP1 (100 mg/kg)
Subjects receive a single intravenous dose of AD-NP1 at 100 mg/kg
干预措施: AD-NP1 (Drug)
Cohort 4 - Placebo
Subjects receive a single intravenous dose of placebo matched in volume to the 100 mg/kg dose of AD-NP1
干预措施: Placebo (Drug)
结局指标
主要结局
Safety and tolerability of escalating doses of a single IV dose of AD-NP1
时间窗: Day of infusion (Day 0) to 28 days post-dose
Assessed by the incidence of treatment-related Adverse Events (AEs) using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
次要结局
- Maximum Tolerated Dose of AD-NP1(Day of infusion (Day 0) to 28 days post-dose)
- Maximum Plasma Concentration (Cmax) as a pharmacokinetics (PK) parameter(Baseline (pre-dose) up to Day 60 post-dose)
- Time to Maximum Plasma Concentration (Tmax) as a pharmacokinetics (PK) parameter(Baseline (pre-dose) up to Day 60 post-dose)
- Area Under the Plasma Concentration-Time Curve (AUC) as a pharmacokinetics (PK) parameter(Baseline (Pre-dose), 30 minutes, 1, 2, 4, 6 hours, and Days 1, 3, 7, 14, 28, 60 post-dose.)
- Terminal Elimination Half-life (T(1/2)) as a pharmacokinetics (PK) parameter(Baseline (pre-dose) up to Day 60 post-dose)
- Total Body Clearance (CL) as a pharmacokinetics (PK) parameter(Baseline (pre-dose) up to Day 60 post-dose)
- Plasma Uridine Concentration(Baseline (pre-dose), and Days 1, 3, 7, 14, and 28 post-dose.)
- Plasma Cytidine Concentration(Baseline (pre-dose), and Days 1, 3, 7, 14, and 28 post-dose.)
- Plasma Orotidine Concentration(Baseline (pre-dose), and Days 1, 3, 7, 14, and 28 post-dose.)
- Plasma Adenine Concentration(Baseline (pre-dose), and Days 1, 3, 7, 14, and 28 post-dose.)
- Plasma Carbamoyl Aspartate Concentration(Baseline (pre-dose), and Days 1, 3, 7, 14, and 28 post-dose.)
- Immunogenicity of a single IV dose of AD-NP1(Baseline (pre-dose) and Days 1, 7, 14, 28, 90, and 180 post-dose)
- Apparent Volume of Distribution (Vd) as a pharmacokinetics (PK) parameter(Baseline (pre-dose) up to Day 60 post-dose)
研究者
Arjun Deb, MD
Professor of Medicine (Cardiology) and Molecular, Cell & Developmental Biology
University of California, Los Angeles