Cocaine Vaccine for the Treatment of Cocaine Dependence in Methadone-Maintained Patients

Abstract

Context Cocaine dependence, which affects 2.5 million Americans annually, has no FDA approved pharmacotherapy. Objective To evaluate the immunogenicity, safety, and efficacy of a novel cocaine vaccine to treat cocaine dependence. Design 24 week Phase IIb randomized double-blind placebo-controlled trial with efficacy assessed during weeks 8 to 20 and follow-up to week 24. Setting Cocaine and opioid dependent persons recruited from 2003–2005 from greater New Haven, CT. Participants 115 methadone maintained subjects (67% male, 87% Caucasian, aged 18–46) were randomized to vaccine or placebo and 82% completed the trial. Most smoked crack cocaine along with using marijuana (18%), alcohol (10%), and non-prescription opioids (44%). Intervention Over 12 weeks 109/115 subjects received five vaccinations of placebo or succinylnorcocaine linked to cholera B protein. Main Outcome Measure Semi-quantitative urinary cocaine metabolite levels measured thrice weekly with positive cutoff of 300 ng/ml. Results The 38% of vaccinated subjects who attained serum IgG anti-cocaine levels ≥ 43 µg/mL (high IgG) had significantly more cocaine-free urines than those with < 43 µg/mL (low IgG) and the placebo subjects during weeks 9 to 16 (45% vs 35%). The proportion of subjects having a 50% reduction in cocaine use was significantly greater in the high IgG than low IgG subjects (0.53 vs. 0.23) (P<0.04). The most common side effects were injection site induration and tenderness. There were no treatment related serious adverse events, withdrawals, or deaths. Conclusions Attaining high (≥ 43 µg/mL) IgG anti-cocaine antibody levels was associated with significantly reduced cocaine use, but only 38% of the vaccinated attained these IgG levels and they had only 2 months of adequate cocaine blockade. Thus, we need improved vaccines and boosters.

Opioid Dose- and Route-Dependent Efficacy of Oxycodone and Heroin Vaccines in Rats

“…These concentrations are higher than have generally been reported with nicotine or cocaine vaccines using similar linkers and carrier proteins, suggesting that opioid-based haptens are particularly immunogenic, perhaps due to their larger size (Kantak et al, 2000;Keyler et al, 2008;Roiko et al, 2008;Pravetoni et al, 2012a). In clinical trials of nicotine or cocaine vaccines, serum antibody concentrations have been considerably lower than those elicited in animals and this likely contributed to their limited efficacy in reducing smoking or cocaine use (Martell et al, 2009;Hatsukami et al, 2011;Esterlis et al, 2013). If opioid vaccines prove more immunogenic than nicotine or cocaine vaccines in humans this could substantially improve their chances of showing clinical efficacy against opioid abuse, but this has to be addressed in humans.…”

Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo

“…The assay sensitivity limit was 150 RNA copies per mL. order of 10 μg/mL, which other studies suggest should be readily achievable by vaccination (24). However, the SHIV/macaque model uses a high-dose challenge (300 TCID 50 ), whereas the viral inoculum found in most human exposures has been estimated to be at least 100-fold less (lower than 3 TCID 50 ) (14,17).…”

BAP updated guidelines: evidence-based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity: recommendations from BAP

“…There is a published 24-week phase RCT of a cocaine vaccine in methadone maintenance patients (Martell et al, 2009) (Ib). Five vaccinations were given over 12 weeks; 38% of patients achieved high IgG levels with significant reduction in cocaine use, although this treatment would be expected to remain effective for 2 months only.…”