A Phase 1, Open-label Positron Emission Tomography Trial to Assess Changes in Liver Uptake of [68Ga]Ga-FAPI-46 Following Oral Administration of Single Doses of AZD2389 to Patients With Advanced Liver Fibrosis (PECHORA).
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 8
- 试验地点
- 2
- 主要终点
- Occupancy, %: percent change from baseline in uptake of FAP PET radioligand [68Ga]Ga-FAPI-46 in the liver after a single dose of AZD2389.
研究概览
简要总结
This is a phase 1, open-label, PET trial. The study is designed to investigate the effect of AZD2389 on FAP occupancy in the liver in participants with advanced liver fibrosis.
详细描述
This is a phase 1, open-label, PET trial in male and female patients with advanced liver fibrosis. The trial will consist of up to 3 sequential panels: Part A (Pilot panel), Part B (Main panel - 3 dose levels of AZD2389, 2 participants per dose level.), and Part C (optional panel). The design of the trial is adaptive and adjustments in time points and/or number of assessments and samples can be made during the course of the trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is an open-label trial.
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female (of non-childbearing potential) participant aged ≥ 20 years and willing and able to give written informed consent for participation in the trial.
- •History confirming compensated liver cirrhosis.
- •Females must have a negative pregnancy test.
- •Barrier contraceptives use by males.
排除标准
- •A condition that would interfere with evaluation of the trial intervention, put the participant at risk, influence the participant's ability to participate or affect the interpretation of the results of the trial.
- •Any clinically significant illness, medical or major surgical procedure or trauma prior randomization.
- •Hepatitis B , hepatitis C and/or HIV infection.
- •Significant elevations in liver blood test, MELD score >12 and platelets <100 x109/L g).
- •eGFR) < 60 ml/min/1.73m
- •History of decompensated liver cirrhosis.
- •Any participants with an aetiology of liver cirrhosis where the Investigator considers that PET signal uptake may be impacted.
- •History of bleeding disorders and major bleeding risk.
- •History of severe dermatological disorders or wound healing.
- •Positive screening result for drugs of abuse or alcohol.
研究组 & 干预措施
Part B1
In Part B1, eligible participants who completed the first PET scan at the screening visit and/or Part A will return to the trial site for blood sampling for FAP concentration analysis and the second PET examination on Day 1 (Visit 3) using the radioligand [68Ga]Ga-FAPI-46. At Visit 4, on Day 7 (±2 days), participants will receive a single oral dose of AZD2389. After AZD2389 administration, the third PET examination will be performed at the PET Centre followed by blood sampling for PK analysis and FAP activity, after which the participants will return to the trial site for further follow-up and safety monitoring. The participants will then be discharged from the trial site. Two follow up visits will occur after administration of AZD2389. Visit 5 (7 days [±2 days]) and Visit 6 (30 days[+7 days]) will monitor for safety and follow-up of AEs.
干预措施: PET scan and radioligand (Diagnostic Test)
Part B2
In Part B2, eligible participants who completed the first PET scan at the screening visit and/or Part A will return to the trial site for blood sampling for FAP concentration analysis and the second PET examination on Day 1 (Visit 3) using the radioligand [68Ga]Ga-FAPI-46. At Visit 4, on Day 7 (±2 days), participants will receive a single oral dose of AZD2389. After AZD2389 administration, the third PET examination will be performed at the PET Centre followed by blood sampling for PK analysis and FAP activity, after which the participants will return to the trial site for further follow-up and safety monitoring. The participants will then be discharged from the trial site. Two follow up visits will occur after administration of AZD2389. Visit 5 (7 days [±2 days]) and Visit 6 (30 days[+7 days]) will monitor for safety and follow-up of AEs.
干预措施: PET scan and radioligand (Diagnostic Test)
Part B3
In Part B3, eligible participants who completed the first PET scan at the screening visit and/or Part A will return to the trial site for blood sampling for FAP concentration analysis and the second PET examination on Day 1 (Visit 3) using the radioligand [68Ga]Ga-FAPI-46. At Visit 4, on Day 7 (±2 days), participants will receive a single oral dose of AZD2389. After AZD2389 administration, the third PET examination will be performed at the PET Centre followed by blood sampling for PK analysis and FAP activity, after which the participants will return to the trial site for further follow-up and safety monitoring. The participants will then be discharged from the trial site. Two follow up visits will occur after administration of AZD2389. Visit 5 (7 days [±2 days]) and Visit 6 (30 days[+7 days]) will monitor for safety and follow-up of AEs.
干预措施: PET scan and radioligand (Diagnostic Test)
Part B2
In Part B2, eligible participants who completed the first PET scan at the screening visit and/or Part A will return to the trial site for blood sampling for FAP concentration analysis and the second PET examination on Day 1 (Visit 3) using the radioligand [68Ga]Ga-FAPI-46. At Visit 4, on Day 7 (±2 days), participants will receive a single oral dose of AZD2389. After AZD2389 administration, the third PET examination will be performed at the PET Centre followed by blood sampling for PK analysis and FAP activity, after which the participants will return to the trial site for further follow-up and safety monitoring. The participants will then be discharged from the trial site. Two follow up visits will occur after administration of AZD2389. Visit 5 (7 days [±2 days]) and Visit 6 (30 days[+7 days]) will monitor for safety and follow-up of AEs.
干预措施: AZD2389 (Drug)
Part B3
In Part B3, eligible participants who completed the first PET scan at the screening visit and/or Part A will return to the trial site for blood sampling for FAP concentration analysis and the second PET examination on Day 1 (Visit 3) using the radioligand [68Ga]Ga-FAPI-46. At Visit 4, on Day 7 (±2 days), participants will receive a single oral dose of AZD2389. After AZD2389 administration, the third PET examination will be performed at the PET Centre followed by blood sampling for PK analysis and FAP activity, after which the participants will return to the trial site for further follow-up and safety monitoring. The participants will then be discharged from the trial site. Two follow up visits will occur after administration of AZD2389. Visit 5 (7 days [±2 days]) and Visit 6 (30 days[+7 days]) will monitor for safety and follow-up of AEs.
干预措施: AZD2389 (Drug)
Part B1
In Part B1, eligible participants who completed the first PET scan at the screening visit and/or Part A will return to the trial site for blood sampling for FAP concentration analysis and the second PET examination on Day 1 (Visit 3) using the radioligand [68Ga]Ga-FAPI-46. At Visit 4, on Day 7 (±2 days), participants will receive a single oral dose of AZD2389. After AZD2389 administration, the third PET examination will be performed at the PET Centre followed by blood sampling for PK analysis and FAP activity, after which the participants will return to the trial site for further follow-up and safety monitoring. The participants will then be discharged from the trial site. Two follow up visits will occur after administration of AZD2389. Visit 5 (7 days [±2 days]) and Visit 6 (30 days[+7 days]) will monitor for safety and follow-up of AEs.
干预措施: AZD2389 (Drug)
Part A
In Part A, eligible participants (screening Visit 1) will return to the trial site for pre-assessments, confirmation of eligibility criteria, blood sampling for FAP concentration analysis (at the trial site), and the first PET examination (screening Visit 2). The participants will perform the PET examination at the PET Centre using the radioligand [68Ga]Ga-FAPI-46. Depending on the results of the initial PET examination, participants of Part A may be invited to continue the trial in Part B. In such a case they will participate in a total of 3 PET examinations, not exceeding predefined radiation exposure limits. If they do not participate further, they will complete the trial with a follow-up visit (Visit 3, telephone call) 7 days (±2 days) after the PET examination.
干预措施: PET scan and radioligand (Diagnostic Test)
Part C
In Part C (optional), participants attend the trial site during Visit 1 (screening, Day-35 to Day-14) to undergo an eligibility check. At Visit 2, the first PET examination with radioligand will be performed at least 5 days before IMP administration. At Visit 3 (Day 1), participants receive a single dose AZD2389, then undergo a second PET examination using the radioligand on Day 2, along with blood sampling for PK analysis and FAP activity. At Visit 4 (Day 8 ±2 days), participants will be admitted to the trial site for a second single dose, then undergo a third PET examination using the radioligand on Day 9, along with blood sampling. At Visit 5 (7 days ±2 days after the PET examination on Visit 4) and Visit 6 (30 days [+7 days]) after the drug administration on Visit 4), follow-up visits at the trial site take place for safety monitoring and follow-up of any AEs.
干预措施: AZD2389 (Drug)
Part C
In Part C (optional), participants attend the trial site during Visit 1 (screening, Day-35 to Day-14) to undergo an eligibility check. At Visit 2, the first PET examination with radioligand will be performed at least 5 days before IMP administration. At Visit 3 (Day 1), participants receive a single dose AZD2389, then undergo a second PET examination using the radioligand on Day 2, along with blood sampling for PK analysis and FAP activity. At Visit 4 (Day 8 ±2 days), participants will be admitted to the trial site for a second single dose, then undergo a third PET examination using the radioligand on Day 9, along with blood sampling. At Visit 5 (7 days ±2 days after the PET examination on Visit 4) and Visit 6 (30 days [+7 days]) after the drug administration on Visit 4), follow-up visits at the trial site take place for safety monitoring and follow-up of any AEs.
干预措施: PET scan and radioligand (Diagnostic Test)
结局指标
主要结局
Occupancy, %: percent change from baseline in uptake of FAP PET radioligand [68Ga]Ga-FAPI-46 in the liver after a single dose of AZD2389.
时间窗: PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days)
To examine target FAP occupancy in the liver by AZD2389 as measured with \[68Ga\]Ga-FAPI-46 PET.
次要结局
- Plasma concentrations of AZD2389.(PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days))
- AZD2389 PK parameters calculated by: the plasma concentration vs. time curve (AUC) from 0 to infinity (AUCinf) and maximum observed concentration (Cmax)(PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days))
- % FAP inhibition compared to baseline in plasma.(PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days))
- % aTRV (for radioligand uptake).(PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days))
- ICC (for radioligand uptake).(PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days))
- Maximum possible target occupancy (Occmax).(PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days))
- The IC50 confidence interval(PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days))