A double blind, placebo-controlled, multi-centre study to evaluate the efficacy, safety, tolerability and immunogenicity of repeated s.c administrations of 100µg NIC002 vaccine in cigarette smokers who are motivated to quit smoking

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-006741-40-DE
• Date of registration: 10/04/2008
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A double blind, placebo-controlled, multi-centre study to evaluate the efficacy, safety, tolerability and immunogenicity of repeated s.c administrations of 100µg NIC002 vaccine in cigarette smokers who are motivated to quit smoking
• Scientific title: A double blind, placebo-controlled, multi-centre study to evaluate the efficacy, safety, tolerability and immunogenicity of repeated s.c administrations of 100µg NIC002 vaccine in cigarette smokers who are motivated to quit smoking
• Date of first enrolment: 14/07/2008
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-006741-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
1.Healthy male and female smoking subjects age 18 to 65 years of age included, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, spirometry and laboratory tests at screening. Subjects with medically managed hypertension or hypercholesterolemia may be included in the study.
2.Subjects must be smoking 10 or more cigarettes per day during the past 12 month prior to the week 0, with no period of abstinence longer than 7 days in the last 3 months prior to week 0.
3.The exhaled breath carbon monoxide (CO) concentration must be 10 ppm or more at screening.
4.The Fagerström Test for Nicotine Dependence (FTND) should indicate at least a moderate level of nicotine dependence which is a score of 5 or above at screening.
5.Subjects must agree to quit smoking by TQD.
6.At screening vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the subject has rested for at least three (3) minutes, Investigators can be guided by the following ranges:
systolic blood pressure, 90-140 mm Hg
diastolic blood pressure, 50-90 mm Hg
pulse rate, 45 - 100 bpm
7.Female subjects must be postmenopausal with no regular menstrual bleeding for at least one (1) year prior to initial dosing. Menopause will be confirmed by a plasma FSH level of >40 IU/L at screening.
OR
Female subjects must have been surgically sterilized at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the CRF. If female subjects have male partners who have undergone vasectomy, the vasectomy must have occurred more than six (6) months prior to first dosing.
8.Male subjects must be using two acceptable methods of contraception (e.g., spermicidal gel plus condom) for the entire duration of the study, up to the Study Completion visit, and refrain from fathering a child in the three (3) months following the last study drug administration. Periodic abstinence and withdrawal are not acceptable methods of contraception.
9.Subjects must have a body mass index (BMI) within the range of 18 to 35 kg/m2. See Appendix 3 of this protocol for BMI ranges.
10.Subjects must be able to communicate well with the investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Attempted to quit smoking in the three (3) months prior to week 0.
2.Use of smoking cessation aid, i.e. nicotine replacement therapy (NRT), bupropion, clonidine, nortryptiline or varenicline in the previous 3 months. Use of any other nicotine vaccine prior to the study. Use of NRT products during the study which are available OTC must be discouraged. Subjects using NRT can stay in the study. Use of NRT will be specifically checked by the investigator and documented on the NRT eCRF page.
3.Use of any other vaccine based on the Qbeta virus like particle.
4.Any surgical or medical condition which may jeopardize the subject in case of participation in the study. The Investigator should make this determination in consideration of the subject’s medical history and/or clinical or laboratory evidence of any of the following:
•History of autoimmune or immunological disorders, immune deficiency. ANA at screening with a titer in the abnormal range for the lab (generally > 1:40).
•History of multiple and recurring allergies or allergy to the investigational compound/compound class being used in this study.
•Significant cardiovascular disease including but not limited to angina pectoris, congestive heart failure, uncontrolled arterial hypertension, clinically significant heart murmurs, clinical significant arrhythmia or previous angioplasty or coronary artery bypass surgery
•Significant hepatic disease.
•Significant renal disease, i.e. history or laboratory findings indicating renal impairment.
•Significant hematological disorder.
•Significant pulmonary disease.
•History of malignancy (excluding non-melanoma skin cancer and cured cervical cancer).
•Organic neurological disorder or significant psychiatric disorder, especially presence of symptoms of depression or history of clinically significant depressive episodes during the last 10 years, and only if medical treatment for more than one month was required.
•Women who are of child bearing potential, pregnant or breast feeding.
•Individuals with high occupational aluminium exposure for example during aluminium manufacturing.
•Donation or loss of 400 ml or more of blood within four (4) weeks prior to initial dosing, or longer if required by local regulation.
•Significant acute illness or surgery within two (2) weeks prior to initial dosing.
5.Concomitant medications for acute conditions at the time of screening are excluded – the inclusion of a subject into the study must be deferred until the condition is resolved and the acute medication terminated. Use of any concomitant medication which contains aluminium for example antacids, some aspirin preparations are not permitted. Any other medication that has been received in a stable manner will be allowed and must be documented in the CRF (e.g. anti-hypertensives and cholesterol lowering medication).
6.Use of psychoactive drug (excluding sleeping pills) within one month before enrolment
7.Any planned surgical intervention during the study period (excluding surgical intervention for minor procedures and only if ambulatory).
8.Participation in any clinical investigation within eight (8) weeks prior to initial dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations.
9.History of a positive HIV (ELISA and Western blot) Hepatitis B surface antigen (HBsAg) or Hepatitis C test result at screening.
10.History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of s

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Smokers

Intervention(s)

Product Code: NIC002
Pharmaceutical Form: Powder for suspension for injection
Current Sponsor code: NIC002
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0,3-
Pharmaceutical form of the placebo: Suspension for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: To test the hypothesis that treatment with NIC002 increases the 4-week rate of continuous abstinence from smoking between weeks 8 and 12 inclusive compared with placebo

Secondary Objective: •To further evaluate clinical efficacy of NIC002 in smokers willing to quit, as determined by:
-the rate of continuous abstinence from smoking for weeks 8 through 26, weeks 26 though 52 and weeks 8 through 52
-the point-prevalence of abstinence assessed at week 12, 26, 39 and 52, based on self-reported smoking status
•To evaluate safety and tolerability (local and systemic) of s.c. NIC002 in healthy smokers by monitoring of clinical signs and symptoms
•To determine immunogenicity of s.c. NIC002 by determination of titers and titer profiles of specific anti-nicotine antibodies (Ab) in serum
•To investigate the relationship between specific anti-nicotine antibodies titers in serum and clinical efficacy

Primary end point(s): 4-week rate of continuous abstinence between weeks 8 and 12

Secondary ID(s)

CNIC002A2201