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

Antidote Therapeutics, Inc

Status and phase: Enrolling; Phase 1

Conditions: Thromboangiitis Obliterans (Buerger's Disease)

Treatments: Other: Placebo; Biological: ATI-1013 (0.8 g); Biological: ATI-1013 (3.2 g); Biological: ATI-1013 (0.2 g)

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT07215923

5U01DA058547-03 (U.S. NIH Grant/Contract)

ATI-1013-001

Details and patient eligibility

About

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.

Enrollment: 15 estimated patients

Sex: All

Ages: 23 to 59 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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15 participants in 3 patient groups

ATI-1013 (0.2 g)

Experimental group

Description:

Single-ascending-dose Cohort 1. Participants receive a single intravenous (IV) infusion of ATI-1013 0.2 g on Day 1. Randomization within the cohort is 4:1 (ATI-1013:placebo).

Treatment:

Biological: ATI-1013 (0.2 g)

Other: Placebo

ATI-1013 (0.8 g)

Experimental group

Description:

Single-ascending-dose Cohort 2. Participants receive a single IV infusion of ATI-1013 0.8 g on Day 1. Randomization 4:1 (ATI-1013:placebo).

Treatment:

Biological: ATI-1013 (0.8 g)

Other: Placebo

ATI-1013 (3.2 g)

Experimental group

Description:

Single-ascending-dose Cohort 3. Participants receive a single IV infusion of ATI-1013 3.2 g on Day 1. Randomization 4:1 (ATI-1013:placebo).

Treatment:

Biological: ATI-1013 (3.2 g)

Other: Placebo