First-in-human single ascending dose test of ATI-1013 in healthy smokers

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

This study will test a single intravenous dose of the anti-nicotine antibody ATI-1013 versus placebo in healthy adult cigarette smokers to check safety, how long the drug stays in the body, whether it triggers an immune response, and its effects on nicotine levels.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 23 Years to 59 Years
• Sex: All
• Sponsor: Antidote Therapeutics, Inc (industry)
• Locations: 1 site (Overland Park, Kansas)
• Trial ID: NCT07215923 on ClinicalTrials.gov

What this trial studies

This is a first-in-human, single ascending dose, placebo-controlled interventional study in healthy adult smokers. Participants will be admitted to clinic, receive one IV infusion of ATI-1013 or placebo, remain in clinic for at least 48 hours, and then return for scheduled follow-up visits and phone check-ins through Day 84. The study will collect safety data, pharmacokinetics (how long the drug remains in the body), immunogenicity (antibody responses to ATI-1013), and measurements of nicotine levels, alongside participant smoking diaries. Doses tested include 0.2 g, 0.8 g, and 3.2 g of ATI-1013 compared with placebo in sequential cohorts.

Who should consider this trial

Good fit: Ideal participants are healthy adult smokers aged 23–59 who currently smoke at least 10 cigarettes per day for two or more years, meet the BMI and weight requirements, and agree to the contraception and visit requirements.

Not a fit: People who are non-smokers, have significant medical conditions, are outside the 23–59 age range, pregnant or unwilling to use required contraception, or who have recently abstained from smoking are unlikely to benefit from participating.

Why it matters

Potential benefit: If successful, ATI-1013 could lower circulating nicotine after smoking and potentially reduce nicotine delivery to the brain, supporting new approaches to help people quit smoking.

How similar studies have performed: Passive anti-nicotine antibody approaches have shown promise in preclinical and early-phase work, but no monoclonal anti-nicotine antibody has yet demonstrated clear clinical success for smoking cessation in large trials.

Eligibility criteria

Inclusion Criteria

1. Provides written informed consent before any study procedures
2. Age 23 to 59 years, inclusive
3. Body weight ≥50 kg at Screening
4. Body mass index (BMI) 18.5-29.9 kg/m² at Screening
5. In good health with no medically significant conditions, in the opinion of the Investigator
6. Current smoker, ≥10 cigarettes per day for ≥2 years, with no abstinence \>6 months
7. Female participants must agree not to donate ova during the study and for 90 days after dosing
8. 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
9. Female participants of non-childbearing potential must be surgically sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or tubal ligation) or postmenopausal (≥1 year without menses)
10. Male participants must agree to use contraception and not donate sperm for 90 days after dosing
11. Willing to abstain from all other tobacco products from Day -2 through Day 84
12. Willing to abstain from all other nicotine products from Day -2 through Day 84
13. Willing to abstain from smoking regular cigarettes:

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

Exclusion Criteria

1. Pregnant, breastfeeding, or planning pregnancy
2. Positive serum pregnancy test at Screening or urine pregnancy test on Day -2 (women only)
3. Prior exposure to any anti-nicotine vaccine or antibody
4. Use of mentholated tobacco products within 30 days before Screening, unwilling to refrain during the study
5. History of severe allergic reaction to antibodies or vaccines (including Guillain-Barré syndrome)
6. Received any vaccination within 90 days prior to Screening
7. Clinically significant allergic adverse reaction (seasonal allergies allowed)
8. Use of systemic steroids or immunomodulating drugs within 90 days (inhaled steroids allowed)
9. History of cancer (except treated basal/squamous cell skin cancer), HIV, other immunodeficiency, or autoimmune disease
10. History of drug (excluding nicotine) or alcohol use disorder (DSM-5 criteria)
11. Clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, or psychiatric disorder, as determined by the Investigator
12. Clinically significant abnormal clinical chemistry, hematology, or urinalysis at Screening or Day -2, in the opinion of the Investigator
13. COVID-19 within the past 6 months or ongoing symptoms likely attributable to COVID-19
14. 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
15. Received an investigational product within 30 days (90 days for biologics) or 5 half-lives (whichever is longer) prior to Screening
16. Exhaled carbon monoxide (CO) \<8 ppm at Screening
17. Positive test for hepatitis B surface antigen, hepatitis C antibody, or HIV antibody at Screening
18. Positive urine alcohol test at Screening and/or Day -2
19. Positive urine drug test (e.g., cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids) at Screening and/or Day -2
20. Unwilling to abstain from xanthine-containing products (coffee, tea, cola, chocolate, energy drinks) within 24 hours prior to admission until discharge
21. Unwilling to abstain from alcohol or alcohol-containing products within 24 hours prior to admission until discharge
22. Significant blood donation or blood loss \>500 mL within 56 days before Screening
23. Plasma donation or loss within 30 days prior to Screening through Day 84
24. Hypersensitivity to the study drug, its excipients, or similar products
25. Unable or unwilling to comply with protocol requirements, restrictions, or instructions
26. Currently enrolled in another clinical study

Where this trial is running

Overland Park, Kansas

• Dr. Vince Clinical Research — Overland Park, Kansas, United States (RECRUITING)

Study contacts

• Study coordinator: Leslie OToole

Conditions: Thromboangiitis Obliterans, ATI-1013, Anti-nicotine monoclonal antibody, Nicotine dependence, Tobacco use disorder, Smoking cessation, Smoking reduction, Vascular disease