Table 1.
Active and passive immunization in SUDs.
| Anti-nicotine immunotherapy | |||||
|---|---|---|---|---|---|
| Nr. | CT identifier | I.P. | CT phase | Methods | POM and results |
| 1. | NCT00996034 (18) | NicVAX (3′AmNic-rEPA) | II | Occupancy of β2-nAChR by nicotine at baseline and following the administration of NicVAX 4–400 μg, using [123I]-5-IA-85380 SPECT; N = 11 healthy smokers; open-label | POM: mean of the average nicotine binding at scan 1 and 2 (baseline and 3 months) Results: Nicotine binding to β2-nAChR correlated positively with nicotine injected before but not after vaccination. The daily number of cigarettes and desire for a cigarette decreased after vaccination. |
| 2. | NCT00598325 NCT00318383 (19) | NicVAX | II | Efficacy of NicVAX 200 and 400 μg 4–5 times over 6 months vs. placebo, N = 301 healthy smokers, DBRCT | POM: Anti-nicotine antibody concentration between screening and week 20, and from week 19 to 26, respectively Results: Vaccine recipients with the highest serum antinicotine antibodies level (top 30% AUC) were significantly more likely to attain 8 weeks of continuous abstinence (weeks 19–26) vs. placebo |
| 3. | NCT00369616 (20) | NIC002 | II | Efficacy and tolerability of NIC002 5 i.m injections vs. placebo, N = 341 smokers, DBRCT | POM: Abstinence rate (self-reported and measured by CO in exhaled air), immunogenicity (IgG antibodies measured by ELISA), safety and tolerability Results: The vaccine was safe, well-tolerated, and highly immunogenic after the first injection. The abstinence rate at month 2 was significant in favor of the vaccine., but continuous abstinence between months 2 and 6 was not significantly different. At 12 months, the difference in continuous abstinence rate between I.P. and placebo favored the I.P. only in those with high antibody response. |
| 4. | NCT01304810 (21) | NicVAX | III | N = 300 participants who received 6 injections of NicVAX in previous trials, phase III, DBRCT, follow-up study, observational | POM: nicotine antibody levels 24 months after injection Results: undisclosed |
| 5. | NCT01318668, EudraCT Number: 2010-019381-90 (22) | NicVAX | I/II | Effects of NicVAX 400 μg vs. placebo over CNS activation and behavior following a nicotine challenge, using fMRI, N = 48 participants, smokers of ≥10 cigarettes per day, DBRCT | POM: fMRI at 18 and 20 weeks post-vaccination, and reaction time in a battery of psychomotor tests Results: No difference in brain activity to smoking cues between treatment groups; no effects of acute nicotine challenge were observed, either. |
| 6. | NCT01102114 (23) | NicVAX | III | Efficacy, immunogenicity, and safety of NicVAX as an aid to smoking cessation, N = 1,000 healthy smokers, 6 doses over 6 months, DBRCT | POM: Efficacy of NicVAX in reaching abstinence (by self-report and CO confirmation) during 12 months Results: undisclosed |
| 7. | NCT01178346 (24) | NicVAX | III | Pharmacoeconomic of NicVAX vs. placebo, N = 500, non-randomized | POM: Health-related QoL changes during NicVAX administration – one-year monitoring Results: undisclosed |
| 8. | NCT01672645 (25) | NIC7-001, NIC7-003 | I | Safety and tolerability of NIC7-001/003 vs. placebo, N = 277 healthy smokers, DBRCT | POM: Adverse events (local and systemic) Results: undisclosed |
| 9. | NCT01478893 (26) | SEL-068 | I | Safety and pharmacodynamics of SEL-068 vs. placebo, DBRCT, N = 82 healthy smokers | POM: Frequency and severity of adverse events during 36 weeks Results: undisclosed |
| 10. | NCT00836199 (27) | NicVAX | III | Efficacy, immunogenicity, and safety of NicVAX vs. placebo, N = 1,000, 6 doses over 6 months, DBRCT | POM: One-year abstinence rate under NicVAX as an aid to smoking cessation Results: undisclosed |
| 11. | NCT00218413 (28) | NicVAX | II | Safety and immunogenicity NicVAX 100, 200, 300, or 400 μg, N = 51 smokers, open-label | POM: Antinicotineantibody concentrations from baseline to day 365 Results: undisclosed |
| 12. | NCT00995033, EudraCT Number: 2008-005894-36 (29) | NicVAX, varenicline | IIb | Efficacy and safety of NicVAX/placebo + varenicline, N = 558 healthy smokers | POM: Long term abstinence (1 year) Results: undisclosed |
| 13. | NCT01280968 (30) | NIC002 (NicQBeta) + Aluminum hydroxide vs. placebo | II | Efficacy of NIC002 100 μg 4 injections over 3 months vs. placebo, N = 52 smokers, DBRCT | POM: Vaccine induces percent change in brain nicotine AUC/Cmax/T1/2/initial slope of brain nicotine accumulation after a single/multiple puffs Results: submitted, but yet unpublished |
| 14. | NCT00736047, EudraCT Number: 2007-006741-40 (31) | NIC002 | II | Efficacy, safety, tolerability, and immunogenicity of NIC002 vs. placebo, N = 200 smokers, DBRCT | POM: Smoking status, exhaled CO (12 months) Results: disclosed, but unpublished |
| 15. | NCT00633321, EudraCT Number: 2005-000922-22 (32) | TA-NIC | II | Efficacy and safety of TA-NIC 100 or 250 μg vs. placebo, N = 522 smokers, DBRCT | POM: Smoking quit rate of minimum 4 weeks determined at week 26 (self-report and CO breath test data) Results: submitted, but yet unpublished |
| Immunotherapy for cocaine use disorder | |||||
| 16. | NCT00965263 (33) | TA-CD | II | Evaluation of the relation between antibody titers and the effects of smoked cocaine on rates of intoxication, craving, and cardiovascular effects, TA-CD 82 or 360 μg administered 4 times, N = 10, DBRCT | POM: Cocaine intoxication during 13 weeks (effect evaluated by VAS) Results: Peak plasma antibody levels significantly predicted cocaine's effects. Patients with higher titers of antibodies had an immediate and robust reduction in ratings of VAS, while those in the inferior half showed only non-significant attenuation. Self-reported use of cocaine tended to decrease as a function of antibody titer. Higher antibody titer predicted significantly greater cocaine-induced tachycardia. |
| 17. | NCT00969878, EudraCT Number: 2008-002183-34 (34) | TA-CD | II | Efficacy of TA-CD 82 or 360 μg administered 4 times vs. placebo, N = 300 patients with CUD, DBRCT | POM: Rate of at least 2 weeks cocaine abstinence during weeks 9 to 16 (cocaine-free urines) Results: Almost 3-times fewer high-level anti-cocaine IgG subjects dropped out compared to low-titers subjects. No difference between the three study groups was detected by the POM for the full 16 weeks of the trial. After week 8 more vaccinated than placebo subjects attained abstinence for ≥2 weeks, but not significant. No treatment-related SAE withdrawal was reported. |
| 18. | NCT00142857 (35) | TA-CD | IIb | Efficacy of TA-CD 360 μg administered 5 times vs. placebo, N = 115 CUD patients maintained on methadone, DBRCT | POM: At least 2 weeks cocaine abstinence during weeks 9 to 16 after vaccination Results: Subjects reaching high levels of serum IgG anti-cocaine antibodies (≥43 μg/ml) had significantly more cocaine-free urine samples than those with low levels and those receiving placebo, during weeks 9 to 16. Subjects with a 50% reduction in cocaine use were significantly more in the high IgG titers group vs. low IgG levels. No SAE related to treatment was reported. |
| 19. | NCT02455479 (36) | dAd5GNE | I | Safety and preliminary efficacy of the vaccine vs. placebo, N = 30 (estimated) CUD patients, DBRCT | POM: General and specific safety parameters Results: the trial is ongoing as of February 2022 |
| Immunotherapy for methamphetamine use disorder | |||||
| 20. | NCT01603147 (37) | ch-mAb7F9 | I | Safety of the I.P. vs. placebo, N = 42 healthy volunteers, DBRCT | POM: Adverse events, vital signs, ECG, clinical laboratory testing over 21 weeks Results: undisclosed |
| 21. | NCT05027451 (38) | IXT-m200 | I | Safety, tolerability, and pharmacokinetics of a 3 g single-dose i.v.- administered I.P. vs. placebo, N = 9 healthy subjects, DBRCT | POM: Treatment-related AE assessed by physical examination, ECG, laboratory testing, and vital signs during 127 days Results: undisclosed |
| 22. | NCT03336866 (39) | IXT-m200 | I/II | Efficacy of I.P (6 or 20 mg/kg i.v. dose) to change methamphetamine concentrations in blood and to alter methamphetamine feels vs. placebo, N = 56 MUD, DBRCT | POM: Change in plasma methamphetamine AUC or Cmax after challenges following single i.v doses of I.P. (29 days) Results: submitted, not yet published |
CT, clinical trial; I.P., investigational product; POM, primary outcome measures; DBRCT, double blind randomized clinical trial; β2-nAChR, β2-containing nicotinic acetylcholine receptors; SPECT, single photon emission computed tomography; CNS, central nervous system; AUC, area under curve; QoL, quality of life; i.m, intramuscular; i.v, intravenous; VAS, Visual Analog Scale; CUD, cocaine use disorder; SAE, serious adverse event; ECG, electrocardiogram; AUC, area under the curve; MUD, methamphetamine use disorder.