含热灭活菌的片剂形式治疗性结核病疫苗（V7）的III期、安慰剂对照、随机、双盲试验，每日给药，持续一个月。
Phase III, placebo-controlled, randomized, double-blind trial of tableted, therapeutic TB vaccine (V7) containing heat-killed administered daily for one month.
作者信息
Bourinbaiar Aldar S, Batbold Uyanga, Efremenko Yuri, Sanjagdorj Munkhburam, Butov Dmytro, Damdinpurev Narantsetseg, Grinishina Elena, Mijiddorj Otgonbayar, Kovolev Mikola, Baasanjav Khaliunaa, Butova Tetyana, Prihoda Natalia, Batbold Ochirbat, Yurchenko Larisa, Tseveendorj Ariungerel, Arzhanova Olga, Chunt Erkhemtsetseg, Stepanenko Hanna, Sokolenko Nina, Makeeva Natalia, Tarakanovskaya Marina, Borisova Vika, Reid Alan, Kalashnikov Valeryi, Nyasulu Peter, Prabowo Satria A, Jirathitikal Vichai, Bain Allen I, Stanford Cynthia, Stanford John
机构信息
Immunitor LLC., Peace Avenue 25, Ulaanbaatar, Mongolia.
Misheel Clinic of Lung Surgery, Sonsgolyn Street, Ulaanbaatar, Mongolia.
出版信息
J Clin Tuberc Other Mycobact Dis. 2019 Dec 12;18:100141. doi: 10.1016/j.jctube.2019.100141. eCollection 2020 Feb.
OBJECTIVE
Immunotherapy of tuberculosis (TB) to shorten treatment duration represents an unmet medical need. Orally delivered, tableted TB vaccine (V7) containing heat-killed (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 was evaluated in 152 patients randomized at 2:1 ratio: V7 ( = 100), placebo ( = 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% ( < 0.0001) and 23.1% ( = 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 ( < 0.0001) vs 0.3 kg ( = 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 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).
目的
结核病免疫疗法以缩短治疗时间是一项尚未满足的医疗需求。口服的含热灭活（NCTC 11659）的片剂结核疫苗（V7）在先前的临床研究中已被证明是安全且起效迅速的免疫辅助剂。
方法
对含10μg水解产物的V7进行的III期试验结果在152例患者中进行评估，这些患者按2:1比例随机分组：V7组（n = 100），安慰剂组（n = 52）。两组均接受常规一线或二线抗结核药物，并与每日服用的V7或安慰剂同时给药。
结果
1个月后，V7组和安慰剂组分别有68%（P < 0.0001）和23.1%（P = 0.04）的患者实现分枝杆菌清除。V7组中对药物敏感和耐多药结核病患者的分层转化率分别为86.7%和55.6%，而安慰剂组分别为27.2%和15%。V7组患者平均体重增加2.4kg（P < 0.0001），而安慰剂组平均增加0.3kg（P = 0.18）。血红蛋白水平、红细胞沉降率和白细胞计数的改善明显优于对照组。肝功能测试表明，V7可预防化疗引起的肝损伤。
结论
口服V7安全，可克服与结核病相关的体重减轻和炎症，降低抗结核药物的肝毒性，使痰菌转阴率提高三倍（OR 3.15；95%CI（2.3,4.6）），并将治疗时间缩短至少六倍。可能需要更长时间的随访研究来进一步证实我们的发现（Clinicaltrials.gov：NCT01977768）。
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