今日，科伦博泰公示最新乙型肝炎治疗临床研究方案——《KL060332胶囊在健康受试者中的安全性、耐受性及药代动力学特征的Ia期临床研究》（CTR20200985）：
KL060332胶囊是乙肝病毒核衣壳组装调节剂，拟用于慢性乙型肝炎的治疗。非临床研究数据表明KL060332胶囊可高效、广谱抑制各基因型乙肝病毒增殖，并兼具良好的药代动力学属性和安全性，单药或与已有的治疗慢性乙型肝炎的药物联用有望提升慢性乙型肝炎临床治疗理想终点达标率。目前全球尚无同机制药物获批上市。
主要目的：评价KL060332胶囊在健康受试者中多剂量、单次、多次给药的安全性和耐受性；
次要目的：评价KL060332胶囊在健康受试者中多剂量、单次、多次给药的药代动力学； 评价食物对KL060332胶囊药代动力学的影响；
探索性目的：探索KL060332胶囊在空腹单次给药剂量递增研究中可能的代谢产物；
该临床计划招募96位受试者，试验中心为吉林大学第一医院I期临床试验研究室，PI为丁艳华主任。
该临床申请于2019年05月09日；
随后2019年07月26日获得临床默示许可；
2020年04月09日获得伦理审查同意；
2020年05月27日公示临床方案。
2020年11月更新
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科伦药业在AALSD2020公布一项研究海报——《0824 - DISCOVERY OF KL060332, A POTENTIAL BEST-IN-CLASS HBV CAPSID INHIBITOR》，摘取部分内容如下：
Background: The assembly of core proteins into viral capsids containing viral genome is a critical step during the hepatitis B virus (HBV) life cycle. Targeting capsid assembly has been demonstrated as an effective approach for anti-HBV drug development. Heteroaryldihydropyrimidines (HAPs) are a class of capsid assembly modulators (CAMs) currently being evaluated in clinical trials. KL060332 is an oral and selective HAPs for the treatment of Chronic Hepatitis B.
Methods: In vitro potency of KL060332 against HBV DNA replication was evaluated with HepG2.2.15 cells and HepG2 cells with resistance mutations against nucleos(t)ide analogues or expressing various HBV genotypes. In vivo efficacy was in several mouse models with HBV replication or infection by oral administration of KL060032 at different doses BID. The pharmacokinetic properties of AB-423 were evaluated in age- and weight-matched animal species, including mice, rats, dog and monkey. Single and repeated dose toxicity studies (GLP) were performed with relevant animal species (rats and dogs) to evaluate the safety profile of KL060032.
Results: KL060332 showed potent antiviral activity (EC50 = 5.18 ± 0.88 nM) and low cytotoxicity (CC50 ≥ 150 μM) in HepG2.2.15 cells. It was equally effective against most prevalent HBV genotypes and nucleos(t)ide resistant variants in vitro. KL060332 has been evaluated in several mouse efficacy models with HBV replication or infection. In HDI-HBV mouse model, KL060332 (9 mg/kg, PO, BID) achieved 2.45 and 2.41 log10 viral DNA reduction in plasma and liver on Day 7, respectively. In combination with TAF, KL060332 exhibited better efficacy than each monotherapy. Notably, in AAV-HBV mouse model, KL060332 (6 mg/kg, PO, BID) not only reduced HBV DNA level (~3 log10 decrease, below LLOQ) but also significantly reduced HBeAg and HBsAg levels both in plasma (>1.5 log10 decrease ) and liver after a 28-day treatment. KL060332 also exhibited high potency in uPA/SCID humanized liver mouse model: a 2.3 log10 decrease in viral DNA was observed after dosing at 12.5 mg/kg BID for 28 days. KL060332 possesses favorable PK profiles in multiple animal species. It also shows a promising preclinical safety profile: low drug-drug interaction potential, no hERG inhibition and >200-fold therapeutic windows based on GLP-Tox studies.
Conclusion: KL060332 is a novel oral HBV capsid inhibitor with potent antiviral activity and promising safety profiles that support advancing this candidate to clinical development. Preclinical data suggests KL060332 has the potential to be the best-in-class. Phase 1a dose escalation study of KL060332 is ongoing, and interim results will be available by October 2020.
截至2020年5月，核衣壳抑制剂国内进展方面：
| 公司 | 产品 | 临床分期 | 备注 |
| 东阳光 | Morphothiadin | II | 国产 |
| 齐鲁 | QL-007 | II | 国产 |
| Janssen | JNJ-56136379 | II | 进口 |
| Assembly | ABI-H2158 | I | 进口 |
| 科伦博泰 | KL060332 | I | 国产 |
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