Cocaine dependence, which affects 2.5 million Americans annually, has no FDA approved pharmacotherapy.
To evaluate the immunogenicity, safety, and efficacy of a novel cocaine vaccine to treat cocaine dependence.
24 week Phase IIb randomized double-blind placebo-controlled trial with efficacy assessed during weeks 8 to 20 and follow-up to week 24.
Cocaine and opioid dependent persons recruited from 2003–2005 from greater New Haven, CT.
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%).
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.
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.
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.