A Study to Investigate Safety, Tolerability, and Pharmacokinetics of AZD7503 in Participants With Suspected NASH.
Study Details
Study Description
Brief Summary
The purpose of this study is to measure the safety, tolerability, and PK (measurement of drug activity in the body over time) of AZD7503 injected subcutaneously, and compared to placebo, in participants with suspected NASH, a type of liver disease.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This is a Phase I, randomised, single-blind (in which the study centre staff including the Principal Investigator, remain blinded during the clinical conduct of a given cohort) placebo controlled, multiple ascending dose (MAD) study in male and female participants conducted at multiple centres.
Each participant is expected to be in the study for approximately 24 weeks, including a screening period of up to 4 weeks, a 12-week study intervention period, and a follow-up visit at week 18 (10 weeks following the final dose). Participants will be randomly assigned in a 3:1 ratio to receive AZD7503 or placebo. Study intervention will be administered via subcutaneous injection.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Cohort 1 Dose A cohort: 20 participants; n=15 on AZD7503 dose A, n=5 on Placebo |
Drug: AZD7503
Each participant is expected to be in the study for approximately 24 weeks, including a screening period of up to 28 days, a 12-week study intervention period, and a follow-up visit at week 18 (10 weeks following the final dose). Participants will be randomly assigned in a 3:1 ratio to receive AZD7503 or placebo. Study intervention will be administered via subcutaneous injection.
|
| Other: Cohort 2 Dose B cohort: 20 participants; n=15 on AZD7503 dose B, n=5 on Placebo. |
Drug: AZD7503
Each participant is expected to be in the study for approximately 24 weeks, including a screening period of up to 28 days, a 12-week study intervention period, and a follow-up visit at week 18 (10 weeks following the final dose). Participants will be randomly assigned in a 3:1 ratio to receive AZD7503 or placebo. Study intervention will be administered via subcutaneous injection.
|
| Other: Cohort 3 Dose C cohort: 20 participants n=15 on AZD7503 dose C, n=5 on Placebo. |
Drug: AZD7503
Each participant is expected to be in the study for approximately 24 weeks, including a screening period of up to 28 days, a 12-week study intervention period, and a follow-up visit at week 18 (10 weeks following the final dose). Participants will be randomly assigned in a 3:1 ratio to receive AZD7503 or placebo. Study intervention will be administered via subcutaneous injection.
|
Outcome Measures
Primary Outcome Measures
- Number of subjects with adverse events (AEs) [Up to and including week 19 (from pre-screening to follow-up visit)]
AEs will be collected at all sites visits per SOA.
- Number of subjects with serious adverse events (SAEs) [Up to and including week 18 (from pre-screening to final visit).]
SAEs will be reported and collected as they occur.
Secondary Outcome Measures
- Maximum observed plasma drug concentration (Cmax) [Day 1 to Day 127]
PK parameters to be collected per the SOA.
- Area under the concentration-time curve from time 0 to infinity (AUCinf) for plasma PK [Day 1 to 127]
PK parameters to be collected per the SOA.
- Area under the concentration-time curve over the dosing interval (AUCtau) for plasma PK [Time frame: Day 1 to 127]
PK parameters to be collected per the SOA.
- Fraction of the dose excreted unchanged into the urine from time t1 to t2 (fe(t1-t2)) for urine PK [Day 1 and Day 57: Pre-dose and between 0-6 hours, 6-12 hours, 12-24 hours, 24-36 hours and 36-48 hours post-dose]
PK parameters to be collected per the SOA.
Eligibility Criteria
Criteria
Key Inclusion Criteria
-
Biopsy-confirmed NASH diagnosis with CRN score of fibrosis stage of F1 to F3 within the previous 12 months prior to screening or history of fatty liver disease by imaging plus clinical suspicion of NASH based on history of type 2 DM for at least 5 years or overweight/obesity with BMI 25 to 40 kg/m^2 with 2 additional metabolic syndrome components.
-
Males and females of non-child bearing potential.
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Willing to provide written informed consent and comply with study requirements.
Key Exclusion Criteria
-
Evidence of any clinical important condition which in the investigator opinion makes it undesirable for the participant to participate in the study
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Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention
-
History of liver transplant or presence or history of hepatic disease other than NASH or histological or imaging evidence of cirrhosis.
-
Human immunodeficiency virus (HIV) infection, seropositive for Hepatitis B (HBV)virus, seropositive for Hepatitis C virus (HCV)
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History of excessive alcohol consumption
-
Uncontrolled high blood pressure
-
Any clinically important abnormalities in ECG
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Suspected history of illicit drug abuse
-
Clinically important abnormalities in urine and blood laboratory results
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Changes in concomitant medication within 1 month of screening
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Received another investigational drug within 90 days of administration of study intervention in this study
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Has received any chemical entity or investigational drug targeting HSD17B13 (eg, ARO-HSD or ALN-HSD).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Chandler | Arizona | United States | 85224 |
| 2 | Research Site | Montclair | California | United States | 91763 |
| 3 | Research Site | Hialeah | Florida | United States | 33016 |
| 4 | Research Site | Port Orange | Florida | United States | 32127 |
| 5 | Research Site | Atlanta | Georgia | United States | 30349 |
| 6 | Research Site | Indianapolis | Indiana | United States | 46202 |
| 7 | Research Site | Morehead City | North Carolina | United States | 28557 |
| 8 | Research Site | Houston | Texas | United States | 77079 |
| 9 | Research Site | San Antonio | Texas | United States | 78215 |
| 10 | Research Site | San Antonio | Texas | United States | 78229 |
| 11 | Research Site | San Juan | Puerto Rico | 00927 |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Principal Investigator: Eric Lawitz, MD, American Research Corporation
- Principal Investigator: William Sanchez, MD, Floridian Clinical Research
- Principal Investigator: Linda Martinez, MD, Oracle Clinical Research
- Principal Investigator: Niharika Samala, MD, Indiana University
- Principal Investigator: Kathryn Lucas, MD, Lucas Research, Inc.
- Principal Investigator: Anita Kohli, MD, The Institute for Liver Health dba Arizona Liver Health
- Principal Investigator: Mazen Noureddin, MD, Houston Research Institute
- Principal Investigator: Madhavi Rudraraju, MD, Pinnacle Clinical Research
- Principal Investigator: Richard Mohammed, MD, Progressive Medical Research
- Principal Investigator: Grisell Ortiz-Lasanta, MD, FDI Clinical Research
- Principal Investigator: Rizwana Mohseni, MD, Catalina Research Institute, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D9230C00002