| Eligibility |
Inclusion Criteria:
1. Written informed consent must be obtained prior to any screening procedures.
2. Age =18 years and =75 years;
3. PLCO risk >2,5% in 6 years to undergo CT screening;
4. Annual risk of lung cancer =3% ( 6% at 2 years or 12% at 4 years) after the baseline
CT using a second risk model which includes the presence of lung nodules such as the
Brock University model;
5. CRP levels above 3 mg/L;
6. Former smokers or current smokers participating in smoking-cessation-programs or
subjects with incidental diagnosis of undetermined nodules;
7. Subjects must have normal organ and bone marrow function:
1. Haemoglobin = 10.0 g/dL.
2. Absolute neutrophil count (ANC) = 1.5 x 109/L.
3. Platelet count = 100 x 109/L.
4. Total bilirubin = 1.5 x institutional upper limit of normal (ULN).
5. Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT))
and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) =
2.5 x ULN.
Exclusion Criteria:
1. Active infection;
2. Subjects with previous diagnosis of invasive cancer in the 5 years before enrolment;
3. History or evidence of tuberculosis (TB) (active or latent) infection or one of the
risk factors for tuberculosis such as but not limited or exclusive to:
1. History of any of the following: residence in a congregate setting (e.g. jail or
prison, homeless shelter, or chronic care facility), substance abuse (e.g.
injection or noninjection) health-care workers with unprotected exposure to
subjects who are at high risk of TB or subjects with TB disease before the
identification and correct airborne precautions of the subject
2. Close contact (i.e. share the same air space in a household or other enclosed
environment for a prolonged period (days or weeks, not minutes or hours)) with a
person with active pulmonary TB disease within the last 12 months.
3. Evidence of TB infection (active or latent), at Visit 1, determined by purified
protein derivative (PPD) skin test and/or QuantiFERON®-TB Gold (QFT-g) assay as
defined by country guidelines (refer to Determination of Tuberculosis Status,
p.39).
i. If presence of TB (active or latent) is established then treatment (according to
country guidelines for TB treatment or TB treatment with immunomodulating drugs) must
have been initiated or completed prior to randomization per country guidelines.
ii. In the absence of country TB (active or latent) guidelines, the following has been
demonstrated: TB has been treated adequately with antibiotics, cure can be
demonstrated, and risk factors resulting in TB exposure and contracting TB have been
removed (e.g. the subject does not live anymore in high TB exposure setting).
4. Subjects with suspected or proven immunocompromised state, including (a) those with
evidence of Human Immunodeficiency Virus (HIV) infection; subjects on anti-retroviral
therapy are excluded (b) those with any other medical condition which in the opinion
of the investigator places the subject at unacceptable risk for participation in
immunomodulatory therapy; or (c) those requiring systemic or local treatment with any
immune modulating agent in doses with systemic effects e.g. high dose oral or
intravenous steroids (> 20 mg prednisone orally daily for > 30 days, > 5 mg prednisone
orally daily or equivalent dose of intravenous steroid) or high dose methotrexate (>
15 mg weekly). Topical, inhaled, local steroid use in doses that are not considered to
cause systemic effects are permitted.
5. History or current diagnosis of cardiac disease, including any of the following:
- recent myocardial infarction or coronary artery bypass graft (CABG) surgery
within last 6 months,
- uncontrolled congestive heart failure,
- unstable angina (within last 6 months),
- clinically significant (symptomatic) cardiac arrhythmias.
6. Known active or recurrent hepatic disorder including cirrhosis, hepatitis B and C
(positive or indeterminate central laboratory results).
7. Prior treatment with canakinumab or drugs of a similar mechanism of action (IL-1ß
inhibitor).
8. Subjects who received any biologic drugs targeting the immune system at any time.
9. All conditions contraindicating canakinumab according to summary of product
characteristics according to EMA
10. History of hypersensitivity to drugs of similar chemical classes or to canakinumab or
its excipients that contraindicates the subject's participation.
11. Any life-threatening condition with life expectancy < 5 years that might prevent the
subject from completing the study
12. Pregnant or nursing women, where pregnancy is defined as the state of a female after
conception and until the termination of gestation, confirmed by a positive hCG
laboratory test
13. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using basic methods of contraception during dosing
of study treatment and for up to 3 months after last dose of study drug. Basic
contraception methods include:
1. Total abstinence (when this is in line with the preferred and usual lifestyle of
the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception
2. Male sterilization (at least 6 months prior to screening).
3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps).
4. Use of oral, injected or implanted hormonal methods of contraception or other
forms of hormonal contraception that have comparable efficacy (failure rate <1%),
for example hormone vaginal ring or transdermal hormone contraception or
placement of an intrauterine device (IUD) or intrauterine system (IUS). In case
of use of oral contraception women should have been stable on the same pill for a
minimum of 3 months before taking study treatment.
14. Subject with nodules larger than 8 mm with Positron emission tomography (PET) SUV >2,5
for which surgical evaluation is indicated.
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