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| Name | Class |
|---|---|
| CTC Clinical Trial Consultants AB | INDUSTRY |
| Karolinska Institutet | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A | Other | 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. |
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| Part B1 | Experimental | 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. |
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| Part B2 | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD2389 | Drug | Doses of AZD2389 will be administrated orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| Occupancy, %: percent change from baseline in uptake of FAP PET radioligand [68Ga]Ga-FAPI-46 in the liver after a single dose of AZD2389. | To examine target FAP occupancy in the liver by AZD2389 as measured with [68Ga]Ga-FAPI-46 PET. | PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma concentrations of AZD2389. | To evaluate plasma PK of AZD2389 after single doses. | 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) |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Stockholm | 17176 | Sweden |
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
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Groups of participants are assigned to receive interventions based on prior milestones being reached in the study, such as in some dose escalation and adaptive design studies.
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This is an open-label trial.
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| Part B3 | Experimental | 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. |
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| Part C | Experimental | 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. |
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| PET scan and radioligand | Diagnostic Test | PET scan and radioligand |
|
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Blood sampling and analysis to evaluate PK plasma of AZD2389 after single doses. |
| PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days) |
| % FAP inhibition compared to baseline in plasma. | To evaluate the plasma target engagement of AZD2389 by assessment of plasma FAP inhibition following single oral dosing. | PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days) |
| % aTRV (for radioligand uptake). | To quantify test-retest reproducibility of radioligand [68Ga]Ga-FAPI-46 uptake in the liver. | PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days) |
| ICC (for radioligand uptake). | To quantify test-retest reproducibility of radioligand [68Ga]Ga-FAPI-46 uptake in the liver. | PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days) |
| Maximum possible target occupancy (Occmax). | A theoretical relationship between average concentration of AZD2389 in plasma during the PET examination and radioligand binding will be assumed to calculate maximum target occupancy, if possible, by curve fitting. | PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days) |
| The IC50 confidence interval | A theoretical relationship between average concentration of AZD2389 in plasma during the PET examination and radioligand binding will be assumed to calculate the confidence interval associated with the IC50. | PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days) |
| ID | Term |
|---|---|
| D008103 | Liver Cirrhosis |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D049268 | Positron-Emission Tomography |
| ID | Term |
|---|---|
| D014055 | Tomography, Emission-Computed |
| D007090 | Image Interpretation, Computer-Assisted |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D007089 | Image Enhancement |
| D010781 | Photography |
| D011877 | Radionuclide Imaging |
| D014054 | Tomography |
| D003947 | Diagnostic Techniques, Radioisotope |
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