Nicotine Dependence
Conditions
Brief summary
The purpose of this study is to find out how vaccine-induced antibodies change the way the body processes nicotine from cigarettes. These antibodies absorb nicotine and can reduce nicotine levels in the brain. In this way, the vaccination may help to quit smoking. The central hypothesis is that anti-nicotine antibodies change kinetics of brain nicotine accumulation and distribution of nicotine between the brain and other body tissues. This vaccine is investigational which means that it is still being tested in research studies and is not approved by the U.S. Food and Drug Administration (FDA) to help people quit smoking.
Interventions
BIOLOGICALNIC002 in Aluminum hydroxide (Alum)
Fifty-five subjects will receive 4 subcutaneous injections of 0.1 mg Nicotine-QB (NIC002) in Alum vaccine with a 4-week interval between injections.
BIOLOGICALPlacebo Vaccine - Aluminum hydroxide
Ten subjects will receive 4 subcutaneous injections of indistinguishable placebo (Alum alone) with a 4-week interval between injections.
Sponsors
Wake Forest University Health Sciences
Novartis Pharmaceuticals
Alexey Mukhin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* 18-55 years old * Smoked an average of at least 10 cigarettes per day for the past year * Have an expired air Carbon Monoxide (CO) reading of at least 15 ppm * Express a desire to quit smoking in the next three to four months. * Potential subjects must agree to use acceptable contraception during their participation in this study. * Potential subjects must agree to avoid the following during their participation in this study: * participation in any other nicotine-related modification strategy outside of this protocol * use of tobacco products other than cigarettes, including pipe tobacco, cigars, snuff, and chewing tobacco * use of experimental (investigational) drugs or devices; * use of illegal drugs; * use of psychiatric medications; * use of opiate medications; * use of systemic steroids or other immunosuppressive agents.
Exclusion criteria
1. Hypertension (systolic \>140 mm Hg, diastolic \>100 mm Hg, coupled with a history of hypertension); subjects with no previous diagnosis of hypertension may have a screening blood pressure up to 160/100. 2. Hypotension with symptoms (systolic \<90 mm Hg, diastolic \<60 mm Hg). 3. Participants with a history of hypertension may, however, be allowed to participate in the study if the study physician or physician assistant determines that the condition is stable, controlled by medication, and in no way jeopardizes the individual's safety. 4. Coronary heart disease or other cardiovascular disorder; 5. Lifetime history of heart attack; 6. Cardiac rhythm disorder (irregular heart rhythm); 7. Chest pains (unless history, exam, and Electrocardiogram (ECG) clearly indicate a non-cardiac source); 8. Cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure); 9. Liver or kidney disorder (except kidney stones, gallstones); 10. Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn; 11. Active ulcers in the past 30 days; 12. Lung disorder (including but not limited to chronic obstructive pulmonary disease (COPD), emphysema, and asthma); 13. Brain abnormality or other neurological disorder (including but not limited to stroke, brain tumor, and seizure disorder); 14. Recent, unexplained fainting spells; 15. Problems giving blood samples; 16. Diabetes treated with insulin; non-insulin treated diabetes (unless glucose is less than 180mg/dcl and HbA1c is less than 7%); 17. Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer); 18. Skin disorder; 19. Autoimmune disease; 20. Human immunodeficiency virus (HIV) or HIV risk behavior; 21. Severe allergies; 22. Other major medical condition; 23. Current psychiatric disease including major depressive episode, panic attack, psychosis, bipolar disorder or eating disorder; 24. Pregnant or nursing mothers; 25. Use (within the past 30 days) of: * Illegal drugs (or if the urine drug screen is positive), * Experimental (investigational) drugs; * Psychiatric medications including antidepressants, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine); * Opiate medications for pain or sleep (non-opiate medication for pain or sleep will be allowed) * Smokeless tobacco (chewing tobacco, snuff), cigars, pipes or e-cigarettes; * Nicotine replacement therapy or any other smoking cessation aid. 26. Alcohol abuse - The AUDIT (Alcohol Use Disorders Identification Test) questionnaire will be used to assess alcohol abuse. 27. Previous history of negative experiences with flu vaccine or any other vaccine. 28. High chronic exposure to aluminum (occupational or medical); 29. Pulmonary function test results \< 60% of predicted value for FEV1 and FVC; 30. Body Mass Index \> 38kg/m2; 31. History of psychosis or bipolar disorder; 32. Prior exposure to CTY002- NicQ or any other nicotine vaccine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vaccine-Induced Percent Change in Brain Nicotine Area Under Curve (AUC) After Single or Multiple (7) Puffs | measured at week 1 and week 16 | There was a 2 hour washout period between the single puff and multiple puffs assessments. |
| Vaccine-Induced Percent Change in Brain Nicotine Maximum Concentration After Single or Multiple (7) Puffs | measured at week 1 and week 16 | There was a 2 hour washout period between the single puff and multiple puffs assessments. |
| Vaccination-Induced Percent Change in T1/2 of Brain Nicotine Accumulation After Single or Multiple (7) Puffs | measured at week 1 and week 16 | There was a 2 hour washout period between the single puff and multiple puffs assessments. |
| Vaccination-Induced Percent Change in Initial Slope of Brain Nicotine Accumulation After a Single Puff | measured at week 1 and week 16 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NIC002 Vaccine in Aluminum Hydroxide 4 subcutaneous vaccinations were performed over the course of 3 months, with 4 weeks between each vaccination. The administered volume of 0.65 mL of sterile water contained 100 μg of NIC002 and 0.46 mg aluminum hydroxide. | 45 |
| Placebo Vaccine - Aluminum Hydroxide 4 placebo injections were administered subcutaneously over the course of 3 months, with 4 weeks between each vaccination. The administered volume of 0.65 mL of sterile water contained 0.46 mg aluminum hydroxide. | 7 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Anxiety | 2 | 0 |
| Overall Study | Commuting Problems | 2 | 0 |
| Overall Study | Lost to Follow-up | 8 | 2 |
| Overall Study | Pre-existing Neurological Condition | 1 | 0 |
| Overall Study | Scheduling Conflicts | 1 | 1 |
| Overall Study | Unable to Follow Experimental Protocol | 2 | 0 |
| Overall Study | Unable to Smoke in Supine Position | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo Vaccine - Aluminum Hydroxide | Total | NIC002 Vaccine in Aluminum Hydroxide |
|---|---|---|---|
| Age, Customized | 44 years | 43 years | 43 years |
| Cigarettes Per Day | 21 cigarettes per day | 19 cigarettes per day | 19 cigarettes per day |
| Pack-Years | 25 pack-years | 22 pack-years | 22 pack-years |
| Region of Enrollment United States | 7 participants | 52 participants | 45 participants |
| Sex: Female, Male Female | 4 Participants | 26 Participants | 22 Participants |
| Sex: Female, Male Male | 3 Participants | 26 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 36 | 3 / 5 |
| serious Total, serious adverse events | 0 / 36 | 0 / 5 |
Outcome results
Primary
Vaccination-Induced Percent Change in Initial Slope of Brain Nicotine Accumulation After a Single Puff
Time frame: measured at week 1 and week 16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NIC002 Vaccine in Aluminum Hydroxide, All Vaccinated Subjects | Vaccination-Induced Percent Change in Initial Slope of Brain Nicotine Accumulation After a Single Puff | 22.5 percentage of change | Standard Error 12.7 |
| NIC002, Tertile With Highest Antibody Binding Capacity | Vaccination-Induced Percent Change in Initial Slope of Brain Nicotine Accumulation After a Single Puff | 9 percentage of change | Standard Error 30 |
| Placebo Vaccine - Aluminum Hydroxide | Vaccination-Induced Percent Change in Initial Slope of Brain Nicotine Accumulation After a Single Puff | 2.4 percentage of change | Standard Error 5.9 |
Primary
Vaccination-Induced Percent Change in T1/2 of Brain Nicotine Accumulation After Single or Multiple (7) Puffs
There was a 2 hour washout period between the single puff and multiple puffs assessments.
Time frame: measured at week 1 and week 16
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NIC002 Vaccine in Aluminum Hydroxide, All Vaccinated Subjects | Vaccination-Induced Percent Change in T1/2 of Brain Nicotine Accumulation After Single or Multiple (7) Puffs | single cigarette puff | 0 percentage of change | Standard Error 11 |
| NIC002 Vaccine in Aluminum Hydroxide, All Vaccinated Subjects | Vaccination-Induced Percent Change in T1/2 of Brain Nicotine Accumulation After Single or Multiple (7) Puffs | multiple cigarette puffs | -2 percentage of change | Standard Error 4 |
| NIC002, Tertile With Highest Antibody Binding Capacity | Vaccination-Induced Percent Change in T1/2 of Brain Nicotine Accumulation After Single or Multiple (7) Puffs | single cigarette puff | 15 percentage of change | Standard Error 30 |
| NIC002, Tertile With Highest Antibody Binding Capacity | Vaccination-Induced Percent Change in T1/2 of Brain Nicotine Accumulation After Single or Multiple (7) Puffs | multiple cigarette puffs | 0 percentage of change | Standard Error 7 |
| Placebo Vaccine - Aluminum Hydroxide | Vaccination-Induced Percent Change in T1/2 of Brain Nicotine Accumulation After Single or Multiple (7) Puffs | single cigarette puff | -4.4 percentage of change | Standard Error 9.6 |
| Placebo Vaccine - Aluminum Hydroxide | Vaccination-Induced Percent Change in T1/2 of Brain Nicotine Accumulation After Single or Multiple (7) Puffs | multiple cigarette puffs | 3.8 percentage of change | Standard Error 11.6 |
Primary
Vaccine-Induced Percent Change in Brain Nicotine Area Under Curve (AUC) After Single or Multiple (7) Puffs
There was a 2 hour washout period between the single puff and multiple puffs assessments.
Time frame: measured at week 1 and week 16
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NIC002 Vaccine in Aluminum Hydroxide, All Vaccinated Subjects | Vaccine-Induced Percent Change in Brain Nicotine Area Under Curve (AUC) After Single or Multiple (7) Puffs | single cigarette puff | 1 percentage of change | Standard Error 5 |
| NIC002 Vaccine in Aluminum Hydroxide, All Vaccinated Subjects | Vaccine-Induced Percent Change in Brain Nicotine Area Under Curve (AUC) After Single or Multiple (7) Puffs | multiple cigarette puffs | 0.1 percentage of change | Standard Error 5.7 |
| NIC002, Tertile With Highest Antibody Binding Capacity | Vaccine-Induced Percent Change in Brain Nicotine Area Under Curve (AUC) After Single or Multiple (7) Puffs | single cigarette puff | -15 percentage of change | Standard Error 7 |
| NIC002, Tertile With Highest Antibody Binding Capacity | Vaccine-Induced Percent Change in Brain Nicotine Area Under Curve (AUC) After Single or Multiple (7) Puffs | multiple cigarette puffs | -9 percentage of change | Standard Error 8 |
| Placebo Vaccine - Aluminum Hydroxide | Vaccine-Induced Percent Change in Brain Nicotine Area Under Curve (AUC) After Single or Multiple (7) Puffs | single cigarette puff | -0.2 percentage of change | Standard Error 7.1 |
| Placebo Vaccine - Aluminum Hydroxide | Vaccine-Induced Percent Change in Brain Nicotine Area Under Curve (AUC) After Single or Multiple (7) Puffs | multiple cigarette puffs | -1.1 percentage of change | Standard Error 9.6 |
Primary
Vaccine-Induced Percent Change in Brain Nicotine Maximum Concentration After Single or Multiple (7) Puffs
There was a 2 hour washout period between the single puff and multiple puffs assessments.
Time frame: measured at week 1 and week 16
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NIC002 Vaccine in Aluminum Hydroxide, All Vaccinated Subjects | Vaccine-Induced Percent Change in Brain Nicotine Maximum Concentration After Single or Multiple (7) Puffs | single cigarette puff | 1 percentage of change | Standard Error 4 |
| NIC002 Vaccine in Aluminum Hydroxide, All Vaccinated Subjects | Vaccine-Induced Percent Change in Brain Nicotine Maximum Concentration After Single or Multiple (7) Puffs | multiple cigarette puffs | -0.7 percentage of change | Standard Error 5.1 |
| NIC002, Tertile With Highest Antibody Binding Capacity | Vaccine-Induced Percent Change in Brain Nicotine Maximum Concentration After Single or Multiple (7) Puffs | single cigarette puff | -15 percentage of change | Standard Error 6 |
| NIC002, Tertile With Highest Antibody Binding Capacity | Vaccine-Induced Percent Change in Brain Nicotine Maximum Concentration After Single or Multiple (7) Puffs | multiple cigarette puffs | -6 percentage of change | Standard Error 9 |
| Placebo Vaccine - Aluminum Hydroxide | Vaccine-Induced Percent Change in Brain Nicotine Maximum Concentration After Single or Multiple (7) Puffs | single cigarette puff | 0 percentage of change | Standard Error 7.8 |
| Placebo Vaccine - Aluminum Hydroxide | Vaccine-Induced Percent Change in Brain Nicotine Maximum Concentration After Single or Multiple (7) Puffs | multiple cigarette puffs | -1.3 percentage of change | Standard Error 9.8 |