초록 ▼

IV. 연구개발결과
Q203의 임상1A상 시험(Q203-TB-PI-US001) ‘Phase 1A, randomized, placebo-controlled, double-blind, dose escalation study to evaluate safety, tolerability, and PK of single doses of Q203 in normal, healthy, male and female subjects’ 는 총 56명의 환자를 대상으로 진행 되었음. 계획된 모든 투약 농도 (10mg, 30mg, 50mg, 100mg

IV. 연구개발결과
Q203의 임상1A상 시험(Q203-TB-PI-US001) ‘Phase 1A, randomized, placebo-controlled, double-blind, dose escalation study to evaluate safety, tolerability, and PK of single doses of Q203 in normal, healthy, male and female subjects’ 는 총 56명의 환자를 대상으로 진행 되었음. 계획된 모든 투약 농도 (10mg, 30mg, 50mg, 100mg, 200mg, 400mg, 800mg)가 특별한 safety issue 와 SAE(serious adverse event) 없이 성공적으로 마무리 되었음. SAD임상 결과를 바탕으로 Q203의 임상 1B상 시험 (Q203-TB-PI-US002) ‘Phase IB, randomized, placebo-controlled, double-blind, multiple ascending dose study to evaluate the safety, tolerability, and PK of Q203 when administered orally to healthy subjects’ 디자인을 도출하였음. 14일 동안 하루 한번 20mg, 50mg, 100mg, 160mg, 250mg, 320mg 의 Q203이 투약 되었으며 특별한 safety issue 와 SAE(serious adverse event) 없이 성공적으로 마무리 되었음. 이를 바탕으로 임상 2A상 시험 protocol을 디자인 하였으며, 최종적으로 임상이 진행 될 남아프리카 공화국 Medicine Control Council 승인을 받음. 향후 개발 과정에 필요한 36개월 안정성 평가 (API, Drug Product), 특허 작성을 위한 Salt screening, 제형 최적화 등을 성공적으로 완료하였음. US FDA기준, 임상 2상 진입에 필요한 in vivo genotoxicity 시험, 여성 환자 모집에 대한 근거 자료가 될 수 있는 in vivo reproductive toxicity 시험, 그리고 28day beagle dog general toxicity시험이 계획한 대로 완료 되었음. 사업화 파트너링에 대한 시도를 지속 적으로 진행 하였으며, 그 결과 향후 개발 과정에 비용 및 학문적 지원을 받을 수 있는 EDCTP funding program에 선정 되었음.

(출처 : 요약문 5p)

Abstract ▼

Q203 is the most potent drug candidate reported (MIC₈₀ < lnM) against both wild type and multi-drug resistant Mycobacterium tuberculosis. Q203 has a novel mechanism of action (target: Cytochrome bcl complex) such that it is positioned as a ‘first-in-class’ candidate for treatment of drug

Q203 is the most potent drug candidate reported (MIC₈₀ < lnM) against both wild type and multi-drug resistant Mycobacterium tuberculosis. Q203 has a novel mechanism of action (target: Cytochrome bcl complex) such that it is positioned as a ‘first-in-class’ candidate for treatment of drug naive and drug resistant tuberculosis (TB) infection. Q203 has potent activity against multi-drug resistant (MDR) and extensively drug resistant (XDR) TB isolated from patients. In addition, Q203 shows potent in vivo efficacy in the acute and chronic mouse infection model (99.9% reduction of lung bacterial load after 4 weeks treatment at 10 mg/kg).
Q203 was tested in a first-in-human (FIH) single ascending dose (SAD) study (Q203-TB-PI-US001). This was a Phase 1A, randomized, placebo-controlled, double- blind, dose escalation study to evaluate safety, tolerability, and PK of single doses of Q203 in normal, healthy, male and female subjects. All dose levels tested (i.e., 10 mg, 30 mg, 50 mg, 100 mg, 200 mg, 400 mg, and 800 mg) were generally well tolerated with no serious adverse events (SAEs) reported during the study. Fifty-six (56) subjects were enrolled, with 8 subjects in Cohort 4 (100 mg Q203 or placebo, fasted) and returned for Cohort 8 (100 mg Q203 or placebo, fed/after a high calorie meal) for food effect assessment. All 56 subjects who received study drug completed all study procedures.
A Phase 1 multiple ascending dose (MAD) clinical study (Q203-TB-PI-US002) in healthy adult volunteers is completed to assess the safety and tolerability of Q203 when administered to subjects for 14 days once daily (QD). All dose levels tested (i.e., 20 mg, 50 mg, 100 mg, 160 mg, 250 mg, and 320 mg) were generally well tolerated with no serious adverse events (SAEs) reported during the study. This study will support 14-day early bactericidal activity (EBA) study with drug sensitive TB patients for early Phase 2 clinical study.
Qurient believes that the totality of nonclinical and clinical safety data available for Q203 support the safety of the proposed phase 2 clinical trial (Q203-TB-P2-ZA001) involving once-daily oral administration of Q203 in treatment-naive patients with sputum smear-positive pulmonary tuberculosis.

(source : Summary 6p)