Multisite Controlled Trial of Cocaine Vaccine

NCT ID: NCT00969878

Last Updated: 2017-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2014-07-31

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.

Conditions

Cocaine Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo injection

TA-CD placebo will be administered intra muscular. A total of 5 injections will be given over 12 weeks (i.e., at Day 1 and at the beginning of Weeks 3, 5, 9 and 13).

Group Type: PLACEBO_COMPARATOR

Placebo Injection

Intervention Type: OTHER

On Day 1, subjects will be randomized to receive placebo injection. Day 1 to Week 16 (3 visits per week) Subsequent placebo injections will be administered at the beginning of Weeks 3, 5, 9 and 13. There should be at least 10 days between injections. Three times per week visits will be scheduled during this period through Week 16. The assessments for the efficacy and safety monitor will be scheduled.Therapy sessions will be provided by a qualified professional such as a master's level counselor.

TA-CD Vaccination

TA-CD 400 μg will be administered intramuscular. A total of 5 injections will be given over 12 weeks (i.e., at Day 1 and at the beginning of Weeks 3, 5, 9 and 13).

Group Type: EXPERIMENTAL

TA-CD Vaccination

Intervention Type: DRUG

On Day 1, subjects will be randomized to receive vaccination. Day 1 to Week 16 (3 visits per week) Subsequent vaccinations will be administered at the beginning of Weeks 3, 5, 9 and 13. There should be at least 10 days between vaccinations. Three times per week visits will be scheduled during this period through Week 16. The assessments for the active phase will be scheduled. Therapy sessions will be provided by a qualified professional such as a master's level counselor.

Interventions

TA-CD Vaccination

On Day 1, subjects will be randomized to receive vaccination. Day 1 to Week 16 (3 visits per week) Subsequent vaccinations will be administered at the beginning of Weeks 3, 5, 9 and 13. There should be at least 10 days between vaccinations. Three times per week visits will be scheduled during this period through Week 16. The assessments for the active phase will be scheduled. Therapy sessions will be provided by a qualified professional such as a master's level counselor.

Intervention Type: DRUG

Placebo Injection

On Day 1, subjects will be randomized to receive placebo injection. Day 1 to Week 16 (3 visits per week) Subsequent placebo injections will be administered at the beginning of Weeks 3, 5, 9 and 13. There should be at least 10 days between injections. Three times per week visits will be scheduled during this period through Week 16. The assessments for the efficacy and safety monitor will be scheduled.Therapy sessions will be provided by a qualified professional such as a master's level counselor.

Intervention Type: OTHER

Other Intervention Names

An aluminium hydroxide gel adjuvant in a saline solution.; An aluminium hydroxide gel adjuvant in a saline solution.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

US Department of Veterans Affairs Cooperative Studies Program

NETWORK

Sponsor Role: collaborator

VA Maryland Health Care System

FED

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: collaborator

VA New York Harbor Healthcare System

FED

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: collaborator

University of Cincinnati

OTHER

Sponsor Role: collaborator

Celtic Pharma Development Services

INDUSTRY

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Thomas R. Kosten, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thomas R Kosten, M.D.

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Locations

Johns Hopkins University

Baltimore, Maryland, United States

NYU Langone Medical Center

New York, New York, United States

Substance Abuse Treatment and Research Service (Downtown)

New York, New York, United States

Cincinnati Addiction Research Center

Cincinnati, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 24793366 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 19805702 (View on PubMed)

Other Identifiers

R01DA025223

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DPMC

Identifier Type: OTHER

Identifier Source: secondary_id

R01DA025223

Identifier Type: NIH

Identifier Source: org_study_id

View Link

NCT00142857

Identifier Type: -

Identifier Source: nct_alias

NCT00218088

Identifier Type: -

Identifier Source: nct_alias