Phase III, placebo-controlled, randomized, double-blind trial of tableted, therapeutic TB vaccine (V7) containing heat-killed M. vaccae administered daily for one month.

ABSTRACT

OBJECTIVE: Immunotherapy of tuberculosis (TB) to shorten treatment duration represents an unmet medical need. Orally delivered, tableted TB vaccine (V7) containing heat-killed Mycobacterium vaccae (NCTC 11659) has been demonstrated in prior clinical studies to be safe and fast-acting immune adjunct. METHODS: The outcome of Phase III trial of V7 containing 10 µg of hydrolyzed M. vaccae was evaluated in 152 patients randomized at 21 ratio V7 (N = 100), placebo (N = 52). Both arms received conventional 1st or 2nd line TB drugs co-administered with daily pill of V7 or placebo. RESULTS: After one month mycobacterial clearance was observed in 68% (P < 0.0001) and 23.1% (P = 0.04) of patients on V7 and placebo. Stratified conversion rates in V7 recipients with drug-sensitive and multidrug-resistant TB were 86.7% and 55.6% vs 27.2% and 15% in placebo. Patients on V7 gained on average 2.4 kg (P < 0.0001) vs 0.3 kg (P = 0.18) in placebo. Improvements in hemoglobin levels, erythrocyte sedimentation rate and leukocyte counts were significantly better than in controls. Liver function tests revealed that V7 can prevent chemotherapy-induced hepatic damage. CONCLUSION: Oral M. vaccae is safe, can overcome TB-associated weight loss and inflammation, reduce hepatotoxicity of TB drugs, improve sputum conversion three-fold OR 3.15; 95%CI (2.3,4.6), and cut treatment length by at least six-fold. Longer follow-up studies might be needed to further substantiate our findings (Clinicaltrials.gov NCT01977768).