Study Assessing Efficacy and Safety of NFL-101 as a Tobacco Cessation Therapy (CESTO2)

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.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation; Nicotine Dependence
• Intervention / Treatment: Drug: NFL-101 dose 1; Drug: NFL-101 dose 2; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 318
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • Centre d'Investigation Clinique de Clermont-Ferrand
  • Dijon, France, 21079
    • CHU de Dijon
  • Gières, France, 38610
    • Eurofins Optimed
  • Lorient, France, 56322
    • Groupe Hospitalier Bretagne Sud
  • Marseille, France, 13015
    • Centre d'Investigation Clinique de Marseille Nord
  • Montpellier, France, 34295
    • Centre d'Investigation Clinique de Montpellier
  • Pessac, France, 33604
    • Centre d'Investigation Clinique de Bordeaux
  • Poitiers, France, 86021
    • Centre d'Investigation Clinique de Poitiers (CIC 1402)
  • Rennes, France, 35000
    • Centre d'Investigation Clinique de Rennes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NFL-101 Dose 1; 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; Subcutaneous injections; Other Names: Tobacco leaf extract
Experimental: NFL-101 Dose 2; 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; Subcutaneous injections; Other Names: Tobacco leaf extract
Placebo Comparator: Placebo; 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; Subcutaneous injections; Other Names: WFI

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: NFL Biosciences SAS
• Investigators: Principal Investigator: Yves Donazzolo, MD, Optimed Eurofins

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2021
• Primary Completion (Actual): April 12, 2024
• Study Completion (Actual): April 12, 2024

Study Registration Dates

• First Submitted: September 15, 2020
• First Submitted That Met QC Criteria: September 24, 2020
• First Posted (Actual): September 30, 2020

Study Record Updates

• Last Update Posted (Actual): June 19, 2025
• Last Update Submitted That Met QC Criteria: June 16, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Tobacco Use Disorder
• Other Study ID Numbers: V10.1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No