Clinical trial NCT00969878: Multisite Controlled Trial of Cocaine Vaccine
Official title: A Double-Blind, Randomized, Placebo-Controlled, Multi-Center Study to Assess the Clinical Efficacy, Safety, and Immunogenicity of a Human Cocaine Vaccine (TA-CD) in the Treatment of Cocaine Dependence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cocaine Dependence
Keywords: Cocaine Vaccine, TA-CD 09
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
name: US Department of Veterans Affairs Cooperative Studies Program
name: VA Maryland Health Care System
name: Columbia University
name: VA New York Harbor Healthcare System
name: University of Pennsylvania
name: Johns Hopkins University
name: University of Cincinnati
name: Celtic Pharma Development Services
First posted: 2009-09-01
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test the efficacy of a newly developed active vaccine against cocaine (TA-CD).

Detailed description: This 18-week, placebo-controlled randomized clinical trial among 300 cocaine dependent patients is designed to test the efficacy of a newly developed active vaccine against cocaine (TA-CD). TA-CD vaccine consists of succinylnorcocaine (SNC) coupled to a recombinant cholera toxin B subunit (rCTB) and is designed to raise anti-cocaine antibodies in the circulation to bind to cocaine entering the bloodstream, following administration by intravenous or intranasal routes or by smoking. The antigen-antibody complexes will be too large to cross the blood-brain barrier, preventing high concentrations of cocaine reaching the brain's nucleus accumbens thereby blocking the pleasurable response to cocaine and reducing rates of drug use. The effectiveness of the vaccine is dependent on inducing sufficient levels of anti-cocaine antibodies to match the challenge from a subsequent dose of cocaine.

Because TA-CD takes several weeks to generate an antibody response, we plan to use contingency management in this interval to sustain treatment engagement. Furthermore, since TA-CD may prove most effective in patients where the antibodies can prevent a cocaine slip from turning into a binge (or return to regular use) by attenuating the priming effect, we are complementing the vaccine by using cognitive behavioral therapy (CBT) to teach patients how to cope with this priming effect and prevent a full relapse.

Eligibility criteria: INCLUSION CRITERIA:

1. Male or female. Females either must be of non-child bearing potential (i.e., surgically sterilized or postmenopausal) or must be using adequate contraception, have a negative pregnancy test, and must agree to continue to use such precautions for 3 months after the last vaccination;
2. Meets DSM-IV-TR criteria for a principal diagnosis of cocaine dependence as confirmed by the MINI;
3. Motivated to discontinue or reduce cocaine use during the period of the study as evidenced both by the judgment of the Investigator or designee and by the subject providing at least 2 urine samples in each of the 2 baseline weeks;
4. In good general health as determined by medical history, general clinical examination, laboratory tests;
5. Has provided written informed consent. Subjects should be cooperative, willing and able to participate and adhere to the Protocol requirements.

EXCLUSION CRITERIA:

1. Subject is cocaine-free (i.e., negative urine results \[BE level\]) during the 2-week screening period;
2. Subject has known immunodeficiency or has a history of autoimmune disease or hypersensitivity to other vaccines. A human immunodeficiency virus (HIV) test must be performed at Screening and reported as negative for HIV-1 and HIV-2;
3. Currently taking medication known to have significant immunosuppressive effects such as systemic glucocorticoids (topical and inhaled formulations are permitted) or oral systemic corticosteroids, within 30 days prior to randomization;
4. Currently taking a dopaminergic, dopamine-blocking, dopamine-modulating, or other central dopamine-altering drug (e.g., antipsychotic drugs); a monoamine oxidase inhibitor (MAOI); or an opiate antagonist;
5. Subject has an unstable medical, neurologic, or psychiatric illness that would interfere with the subject's safety, ability to participate in the study, or the interpretability of data. Subjects who meet the DSM-IV-TR criteria for psychosis, schizophrenia, bipolar disorder or clinically significant suicidal ideation;
6. Subject had dependence on benzodiazepines, barbiturates, opiates or amphetamines according to DSM-IV-TR during the year prior to Screening. Opioid dependence includes methadone or buprenorphine maintenance treatment;
7. Subject requiring medical detox for alcohol dependence;
8. History of sensitivity to aluminium hydroxide gel;
9. History of severe adverse reaction to cholera vaccine;
10. Subject had previous vaccination with TA-CD;
11. Subject received other vaccines, including flu vaccine, within 14 days prior to signing consent;
12. Subject has participated in another clinical trial or received any other investigational compound within 14 days prior to signing consent;
13. Subject has received blood or blood products within the 3 months prior to signing consent;
14. Subject has liver function tests greater than 3 times the upper limit of normal at Screening;
15. Subject has systolic blood pressure higher than 140 mmHg and/or diastolic blood pressure \>90 mmHg;
16. Female subjects with a positive pregnancy test, lactating mothers, women refusing to agree to adequate contraception and pregnancy tests during the study, or women who are planning to become pregnant during the period of the trial. Acceptable contraceptive methods are oral or parenteral hormonal contraceptives, intrauterine device (IUD), or barrier and spermicide, but not abstinence;
17. Male subjects refusing to agree to adequate contraception during the study, or males who are part of a couple planning to become pregnant during the period of the trial;
18. People who are involuntarily detained in a penal institution or people who become involuntarily detained during the study;
19. Any other factor that in the opinion of the Investigator or designee would make the subject unsafe or unsuitable for the study.

Primary outcomes:
measure: Cocaine Abstinence During Weeks 9 to 16 Inclusive
timeFrame: Over 8 weeks ( Study Weeks 9 to 16 inclusive)
Secondary outcomes:
measure: •The Immunogenicity of TA-CD;
timeFrame: During the 18 weeks study period.
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: New york
country: United States
facility: NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: Substance Abuse Treatment and Research Service (Downtown)
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Addiction Research Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Thomas R Kosten, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kosten TR, Domingo CB, Shorter D, Orson F, Green C, Somoza E, Sekerka R, Levin FR, Mariani JJ, Stitzer M, Tompkins DA, Rotrosen J, Thakkar V, Smoak B, Kampman K. Vaccine for cocaine dependence: a randomized double-blind placebo-controlled efficacy trial. Drug Alcohol Depend. 2014 Jul 1;140:42-7. doi: 10.1016/j.drugalcdep.2014.04.003. Epub 2014 Apr 16.
citation: Martell BA, Orson FM, Poling J, Mitchell E, Rossen RD, Gardner T, Kosten TR. Cocaine vaccine for the treatment of cocaine dependence in methadone-maintained patients: a randomized, double-blind, placebo-controlled efficacy trial. Arch Gen Psychiatry. 2009 Oct;66(10):1116-23. doi: 10.1001/archgenpsychiatry.2009.128.