A First in Human Single Ascending Dose (SAD) Study of ATI-1013 in Healthy Smokers

Официальное название

A First in Human, Double-Blind, Placebo-Controlled, Randomized Evaluation of Single Ascending Doses of ATI-1013, a Human Monoclonal Antibody to Nicotine in Healthy Smokers

Обзор

This study is a first-in-human clinical trial of drug ATI-1013, in healthy adult cigarette smokers. The main questions it aims to answer are to learn about the safety of drug ATI-1013, how long drug ATI-1013 remains within the body, does drug ATI-1013 trigger an immune response, and the effects of drug ATI-1013 on nicotine levels within the body. The clinical trial will compare drug ATI-1013 to a placebo (a look-alike substance that contains no drug) to see if drug ATI-1013 has comparable safety. Participants will have a Screening visit (Day -28 to -3) and will be admitted on Day -2. Each participant will receive one intravenous (IV) infusion of ATI-1013 or placebo (Day 1). Participants will remain in-clinic for at least 48 hours post-dose and return for follow-up visits on Days 7, 21, 42, 56, and 84, with telephone check-ins on Days 5, 14, 28, and 70. Participants will keep a diary of their cigarette use and smoking behaviors.

Вмешательства

• Биопрепарат ATI-1013 (0.2 g)
  Single intravenous (IV) infusion of ATI-1013, 0.2 g total dose.
• Биопрепарат ATI-1013 (0.8 g)
  Single IV infusion of ATI-1013, 0.8 g total dose.
• Биопрепарат ATI-1013 (3.2 g)
  Single IV infusion of ATI-1013, 3.2 g total dose.
• Другое Placebo
  Matching placebo (vehicle) IV infusion.

Первичные конечные точки

• Incidence of all adverse events (AEs) [Срок оценки: Day 1 through Day 84]
• Development of Anti-Drug Antibodies [Срок оценки: Baseline (Day -1) through Day 84]

Вторичные конечные точки (12)

• Pharmacokinetics of ATI-1013 Maximum Concentration (Cmax) [Срок оценки: Day 1 through Day 84]
• Pharmacokinetics of ATI-1013 Time to Maximum Concentration (Tmax) [Срок оценки: Day 1 through Day 84]
• Pharmacokinetics of ATI-1013 Area Under the Curve (AUC) [Срок оценки: Day 1 through Day 84]
• Pharmacokinetics of ATI-1013 Half-life (t1/2) [Срок оценки: Day 1 through Day 84]
• Physiologic Responses to Nicotine (Skin Temperature) [Срок оценки: Day -1 and Day 2]
• Physiologic Responses to Nicotine (Heart Rate) [Срок оценки: Day -1 and Day 2]
• Physiologic Responses to Nicotine (Plasma Epinephrine) [Срок оценки: Day -1 and Day 2]
• Physiologic Responses to Nicotine (Blood Pressure) [Срок оценки: Day -1 and Day 2]
• Withdrawal Symptoms Minnesota Tobacco Withdrawal Scale (MTWS) [Срок оценки: Day -1 and Day 2]
• Subjective/Psychological Effects of Nicotine Drug Effect Questionnaire (DEQ) [Срок оценки: Day -1 and Day 2]
• Subjective/Psychological Effects of Nicotine Modified Cigarette Evaluation Questionnaire (mCEQ) [Срок оценки: Day -1 and Day 2]
• Total Nicotine Levels [Срок оценки: Baseline through Day 84]

Критерии участия

Критерии включения

• Provides written informed consent before any study procedures
• Age 23 to 59 years, inclusive
• Body weight ≥50 kg at Screening
• Body mass index (BMI) 18.5-29.9 kg/m² at Screening
• In good health with no medically significant conditions, in the opinion of the Investigator
• Current smoker, ≥10 cigarettes per day for ≥2 years, with no abstinence >6 months
• Female participants must agree not to donate ova during the study and for 90 days after dosing
• Female participants of childbearing potential must use an acceptable, effective method of birth control from 30 days prior to Screening through 90 days after dosing
• Female participants of non-childbearing potential must be surgically sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or tubal ligation) or postmenopausal (≥1 year without menses)
• Male participants must agree to use contraception and not donate sperm for 90 days after dosing
• Willing to abstain from all other tobacco products from Day -2 through Day 84
• Willing to abstain from all other nicotine products from Day -2 through Day 84
• Willing to abstain from smoking regular cigarettes:

• Approximately 18 hours from evening of Day -2
• Approximately 42 hours from evening of Day -1

Критерии исключения

• Pregnant, breastfeeding, or planning pregnancy
• Positive serum pregnancy test at Screening or urine pregnancy test on Day -2 (women only)
• Prior exposure to any anti-nicotine vaccine or antibody
• Use of mentholated tobacco products within 30 days before Screening, unwilling to refrain during the study
• History of severe allergic reaction to antibodies or vaccines (including Guillain-Barré syndrome)
• Received any vaccination within 90 days prior to Screening
• Clinically significant allergic adverse reaction (seasonal allergies allowed)
• Use of systemic steroids or immunomodulating drugs within 90 days (inhaled steroids allowed)
• History of cancer (except treated basal/squamous cell skin cancer), HIV, other immunodeficiency, or autoimmune disease
• History of drug (excluding nicotine) or alcohol use disorder (DSM-5 criteria)
• Clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, or psychiatric disorder, as determined by the Investigator
• Clinically significant abnormal clinical chemistry, hematology, or urinalysis at Screening or Day -2, in the opinion of the Investigator
• COVID-19 within the past 6 months or ongoing symptoms likely attributable to COVID-19
• Use of varenicline, bupropion, nicotine replacement therapy (NRT), or other anti-smoking pharmacologic treatments (including off-label nortriptyline, clonidine, or cytisinicline) within 90 days prior to Screening
• Received an investigational product within 30 days (90 days for biologics) or 5 half-lives (whichever is longer) prior to Screening
• Exhaled carbon monoxide (CO) <8 ppm at Screening
• Positive test for hepatitis B surface antigen, hepatitis C antibody, or HIV antibody at Screening
• Positive urine alcohol test at Screening and/or Day -2
• Positive urine drug test (e.g., cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids) at Screening and/or Day -2
• Unwilling to abstain from xanthine-containing products (coffee, tea, cola, chocolate, energy drinks) within 24 hours prior to admission until discharge
• Unwilling to abstain from alcohol or alcohol-containing products within 24 hours prior to admission until discharge
• Significant blood donation or blood loss >500 mL within 56 days before Screening
• Plasma donation or loss within 30 days prior to Screening through Day 84
• Hypersensitivity to the study drug, its excipients, or similar products
• Unable or unwilling to comply with protocol requirements, restrictions, or instructions
• Currently enrolled in another clinical study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Dr. Vince Clinical Research — Overland Park

Идентификаторы

NCT: NCT07215923 · ATI-1013-001 · 5U01DA058547-03

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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