Study Assessing Efficacy and Safety of NFL-101 as a Tobacco Cessation Therapy

Study Overview
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Brief Summary
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CESTO 2 is a 318 participants, 3-arm, multicentric, randomized, double-blind, placebo-controlled Phase II clinical trial. The main objectives are to select the most efficient dose and to assess long-term efficacy of NFL-101 compared to placebo, for abrupt cessation and for reduction before cessation.

Detailed Description
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Long-term smoking cessation or reduction had been observed in thousands of patients when 1 or 2 subcutaneous injections of a desensitization treatment against tobacco allergy were taking place concomitantly with Target Quit Date (TQD). NFL Biosciences SAS developed a tobacco cessation drug candidate (NFL-101) consisting of a nicotine-free extract of tobacco proteins. According to the observations made during CESTO, a Phase I study on 24 smokers, NFL-101 appears to work by reducing cigarette appetence immediately and over a week after each injection.

Official Title
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Study Assessing Efficacy and Safety of NFL-101 as a Tobacco Cessation Therapy

Conditions
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Smoking Cessation, Nicotine Dependence

Intervention / Treatment
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* Drug: NFL-101 dose 1
* Drug: NFL-101 dose 2
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject ≥ 18 and ≤ 70-year-old; With ECOG/WHO performance status 0-1 (Appendix 1); Subject currently smoking at least 11 cigarettes per day and with a dependency level ≥ 3 according to Fagerström Test for Nicotine Dependence scoring (see Appendix 2) [1]; Subject willing to quit smoking; Good general health (i.e. no uncontrolled medical condition, or no medical condition that could interfere with the conduct and the outcomes of the study, according to the investigator); Good mental health (i.e. no alcohol or drug abuse in the past year, no psychiatric history- adequately treated depression is accepted); For women of childbearing potential: commitment to consistently and correctly use of a highly effective contraceptive measure: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner or sexual abstinence for the duration of the trial; (Females of non-childbearing potential: either surgically sterilized or at least 1 year postmenopausal (amenorrhoea duration at least 12 months)) ; Negative pregnancy test at screening visit; Laboratory parameters within the normal range of the laboratory (hematological, blood chemistry tests). Individual values out of the normal range can be accepted if judged clinically non relevant by the Investigator; Normal ECG recording on a 12-lead ECG at the screening visit: 120 < PR < 210 ms, QRS < 120 ms, QTcf ≤ 430 ms for male and < 450 ms for female, No sign of any trouble of sinusal automatism, Or considered NCs by investigators; Negative prick test at screening visit for the whole study product (extract of Tobacco leaf and NaCL), and positive for histamine; French speaking subject; Covered by Health Insurance System and / or in compliance with the recommendations of National Law in force relating to biomedical research. Subject having signed the informed consent agreement. Exclusion Criteria: Pregnancy and breastfeeding; Concomitant participation to another clinical trial; Concomitant active infectious diseases; Concomitant use of treatment known to interfere with immune response (not including desensitization therapies); Uncontrolled diabetes; Prior exposure to a nicotine vaccine or to any other vaccine within 30 days before study product administration; Concomitant use (and within previous 60 days) of any smoking cessation therapy (including electronic cigarettes and alternative methods such as hypnosis or acupuncture); Legal incapacity or physical, psychological or mental status interfering with the subject's ability to sign the informed consent or to terminate the study. Subject who would receive more than 4500 euros as indemnities for his participation in biomedical research within the 12 last months, including the indemnities for the present study Subject who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NFL-101 Dose 1<br>50 µg per injection (in each arm), two injections at day 1, two injections at day 8, optional injections later on | Drug: NFL-101 dose 1<br>* Subcutaneous injections<br>* Other names: Tobacco leaf extract;|
| Experimental: NFL-101 Dose 2<br>100 µg per injection (in each arm), two injections at day 1, two injections at day 8, optional injections later on | Drug: NFL-101 dose 2<br>* Subcutaneous injections<br>* Other names: Tobacco leaf extract;|
| Placebo Comparator: Placebo<br>The placebo will consist of two syringes containing 1 mL of dilution solution, two injections at day 1, two injections at day 8, optional injections later on | Drug: Placebo<br>* Subcutaneous injections<br>* Other names: WFI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of participants achieving 4-week continuous abstinence | 4-weekcontinuous abstinence measured from D15 to D43 | 4-week | 
| Rate of participants achieving 6-month continuous abstinence | 6-month continuous abstinence measured from D15 to M6 | 6-month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of participants achieving 12-month continuous abstinence | 12-month continuous abstinence measured from D15 to M12 | 12-month | 
| Rate of participants achieving 3-month continuous abstinence | 3-month continuous abstinence measured from D15 to M3 | 3-month | 
| Rate of participants achieving 3-month continuous abstinence End of Treatment | continuous abstinence measured during 3-month after end of treatment | 3-month | 
| Rate of participants achieving 6-month continuous abstinence End of Treatment | continuous abstinence measured during 6-month after end of treatment | 6-month | 
| Rate of participants achieving 3-month continuous abstinence End of Study | continuous abstinence measured from M9 to M12 | 3-month |