Smoking CessationPhase 2CESTO2NCT04571216
Study Assessing Efficacy and Safety of NFL-101 as a Tobacco Cessation Therapy
A Phase 2 study testing NFL-101 dose 1 and NFL-101 dose 2 in people with Smoking Cessation and Nicotine Dependence, run by NFL Biosciences SAS at 9 sites in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Smoking Cessation, Nicotine Dependence
- What is being tested?
- NFL-101 dose 1 and NFL-101 dose 2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 318 participants
- Where
- 9 sitesFrance
- Study dates
- 12 Apr 2021to 12 Apr 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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);
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- 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.
Who cannot join
- 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;
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- 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
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
France9 sites
Centre d'Investigation Clinique de Clermont-Ferrand
Clermont-Ferrand, 63003
CHU de Dijon
Dijon, 21079
Eurofins Optimed
Gières, 38610
Groupe Hospitalier Bretagne Sud
Lorient, 56322
Centre d'Investigation Clinique de Marseille Nord
Marseille, 13015
Centre d'Investigation Clinique de Montpellier
Montpellier, 34295
Centre d'Investigation Clinique de Bordeaux
Pessac, 33604
Centre d'Investigation Clinique de Poitiers (CIC 1402)
Poitiers, 86021
Centre d'Investigation Clinique de Rennes
Rennes, 35000
About this study
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.
Read the 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.
- Conditions
- Smoking Cessation, Nicotine Dependence
- Being tested
- NFL-101 dose 1, NFL-101 dose 2, Placebo
- Medical subject headings
- Smoking Cessation, Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NFL-101 dose 1Drug
Also called Tobacco leaf extract
Subcutaneous injections
NFL-101 dose 2Drug
Also called Tobacco leaf extract
Subcutaneous injections
PlaceboDrug
Also called WFI
Subcutaneous injections
| Study group | Role | What they receive |
|---|---|---|
| NFL-101 Dose 1 | Experimental | 50 µg per injection (in each arm), two injections at day 1, two injections at day 8, optional injections later on Receives: Drug: NFL-101 dose 1 |
| NFL-101 Dose 2 | Experimental | 100 µg per injection (in each arm), two injections at day 1, two injections at day 8, optional injections later on Receives: Drug: NFL-101 dose 2 |
| Placebo | Placebo comparator | 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 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of participants achieving 4-week continuous abstinence
4-weekcontinuous abstinence measured from D15 to D43
Measured: 4-week
Rate of participants achieving 6-month continuous abstinence
6-month continuous abstinence measured from D15 to M6
Measured: 6-month
Secondary outcomes (5)
Rate of participants achieving 12-month continuous abstinence
12-month continuous abstinence measured from D15 to M12
Measured: 12-month
Rate of participants achieving 3-month continuous abstinence
3-month continuous abstinence measured from D15 to M3
Measured: 3-month
Rate of participants achieving 3-month continuous abstinence End of Treatment
continuous abstinence measured during 3-month after end of treatment
Measured: 3-month
Rate of participants achieving 6-month continuous abstinence End of Treatment
continuous abstinence measured during 6-month after end of treatment
Measured: 6-month
Rate of participants achieving 3-month continuous abstinence End of Study
continuous abstinence measured from M9 to M12
Measured: 3-month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2020
- Study start12 Apr 2021
- Primary completion12 Apr 2024
- Study completion12 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Smoking CessationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 318 participants (actual)
Sponsor and investigators
- Lead sponsor
- NFL Biosciences SAS
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Principal investigator, Yves Donazzolo, NFL Biosciences SAS
- Investigators
- Yves Donazzolo, MD, Principal investigator, Optimed Eurofins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04571216
- Sponsor's protocol ID
- V10.1
- Acronym
- CESTO2
- Status last verified
- Jun 2025
- First submitted
- 15 Sep 2020
- Last updated
- 19 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study Assessing Efficacy and Safety of NFL-101 as a Tobacco Cessation Therapy
- ClinicalTrials.gov ID
- NCT04571216
- Acronym / sponsor ID
- CESTO2 / V10.1
- Conditions
- Smoking Cessation, Nicotine Dependence
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 318 participants (actual)
- Lead sponsor
- NFL Biosciences SASIndustry (pharma, biotech, devices)
- Study start
- 12 Apr 2021 (actual)
- Primary completion
- 12 Apr 2024 (actual)
- Study completion
- 12 Apr 2024 (actual)
- First posted
- 30 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| NFL-101 Dose 1 | Experimental | Drug: NFL-101 dose 150 µg per injection (in each arm), two injections at day 1, two injections at day 8, optional injections later on |
| NFL-101 Dose 2 | Experimental | Drug: NFL-101 dose 2100 µg per injection (in each arm), two injections at day 1, two injections at day 8, optional injections later on |
| Placebo | Placebo comparator | Drug: PlaceboThe 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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);
Key exclusion criteria (9 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NFL-101 dose 1Also: Tobacco leaf extractSubcutaneous injections | Drug | NFL-101 Dose 1 |
| NFL-101 dose 2Also: Tobacco leaf extractSubcutaneous injections | Drug | NFL-101 Dose 2 |
| PlaceboAlso: WFISubcutaneous injections | Drug | Placebo |
Primary outcome
Rate of participants achieving 4-week continuous abstinence
Time frame: 4-week
4-weekcontinuous abstinence measured from D15 to D43
Rate of participants achieving 6-month continuous abstinence
Time frame: 6-month
6-month continuous abstinence measured from D15 to M6
5 secondary outcomes
Rate of participants achieving 12-month continuous abstinence
Time frame: 12-month
Rate of participants achieving 3-month continuous abstinence
Time frame: 3-month
Rate of participants achieving 3-month continuous abstinence End of Treatment
Time frame: 3-month
Rate of participants achieving 6-month continuous abstinence End of Treatment
Time frame: 6-month
Rate of participants achieving 3-month continuous abstinence End of Study
Time frame: 3-month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yves Donazzolo, MD principal investigator
Optimed Eurofins
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NFL-101 dose 1 and NFL-101 dose 2 in people with Smoking Cessation and Nicotine Dependence, run by NFL Biosciences SAS at 9 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of participants achieving 4-week continuous abstinence (time frame: 4-week). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2025.