Randomized, placebo-controlled phase II trial of heat-killed Mycobacterium vaccae (Longcom batch) formulated as an oral pill (V7)

Abstract

One-month Phase II trial was conducted in 43 sputum smear-positive patients with pulmonary tuberculosis randomized into treatment (n = 22) and placebo (n = 21) arms to investigate the safety and efficacy of an orally-administered therapeutic TB vaccine (V7) containing 10 μg of heat-killed Mycobacterium vaccae provided by Longcom company. Immunotherapy and control groups comprised 8 newly diagnosed (1stDx TB; 18.6%), 6 re-treated (RTB; 14%), and 29 multidrug-resistant (MDR-TB; 67.4%) cases distributed at 5:4:13 and 3:2:16 ratios, respectively. Both arms received conventional TB drugs administered under directly observed therapy. The average weight gain in V7 arm was modest, but statistically significant (0.6 kg; p = 0.004), while placebo patients lost 0.1 kg (p = 0.77). Except defervescence and increased lymphocyte percentage, other secondary endpoints such as erythrocyte sedimentation rate (ESR), leukocyte counts and hemoglobin content were not significantly affected. In control patients only one secondary endpoint, ESR, has improved. After one month mycobacterial clearance in sputum smears was observed in 31.8% (p = 0.03) and 9.5% (p = 0.83) of patients on V7 and placebo. However, the difference between outcomes in two arms was below significance threshold (p = 0.07). Thus, larger population of patients with prolonged follow-up is required to support these preliminary findings.

Keywords: :

• inflammation
• mycobacterium tuberculosis
• drug-resistant TB
• therapeutic vaccine
• immunomodulator
• mucosa
• DOT
• imm02
• NCT01380119

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed

Acknowledgments

We thank all volunteers who participated in this study. The wholehearted support of clinicians, nurses and lab personnel who contributed their effort made this study possible. Our gratitude is expressed to many experts in TB and immunology fields who kindly shared with us their opinions and critiques prior to and after this study was completed. We are greatly indebted to Jiang Pu, Feng-li Tao, Shilong Yang, Haiming Wei, Chuanyou Li, Vika Borisova, Alan Reid and Allen Bain for their generosity and tireless assistance in procuring a sample of Vaccae^®, which has been used for making the batch of V7 used in this trial.