Non-alcoholic Fatty Liver DiseasePhase 1NCT05560607
Knockdown of HSD17B13 mRNA, Pharmacokinetics, Safety, and Tolerability, of AZD7503 in Non-Alcoholic Fatty Liver Disease
A Phase 1 study testing AZD7503 Intervention in people with Non-alcoholic Fatty Liver Disease and Fatty Liver, Nonalcoholic, run by AstraZeneca at 1 site in United States.
Trial summary
This is a two-part study. In Part A, eligible participants will undergo a baseline diagnostic liver biopsy to determine non-alcoholic fatty liver disease (NAFLD) Activity Score (NAS) and fibrosis stage, but will not receive study intervention. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease, Fatty Liver, Nonalcoholic, NAFLD
- What is being tested?
- AZD7503 Intervention
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Aug 2022to 27 Feb 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant must be ≥ 18 to ≤ 70 years of age at the time of signing the informed consent.
- Participants with suspected or confirmed NAFLD or NASH including laboratory values with any of the following deviations at screening
- ALT > ULN,
- Imaging demonstrating hepatic steatosis including controlled attenuation parameter (CAP) >290 dB/m, OR Liver stiffness of >7.1 kPa as measured by Fibroscan.
- Body mass index (BMI) ≥20 kg/m2.
- Male and /or female of non-child bearing potential.
- Histologic evidence of NAFLD or NASH with a NAS ≥3 following baseline liver biopsy.
Who cannot join
- History or presence of hepatic disease (with the exception of hepatic steatosis, NASH) or evidence of other known forms of known chronic liver
- History of liver transplant, evidence of cirrhosis, or current placement on a liver transplant
- Positive results for HIV antigen and hepatitis B surface antigen If a participant has a positive result at the screening visit for hepatitis C antibody, the investigator will document that the participant has hepatitis C RNA below the limit of detection and has not received curative treatment in the last 3 years.
- History of alcohol abuse or excessive intake of alcohol as judged by the investigator.
- Uncontrolled blood pressure, defined as any of the following during pre-screening and/or Day -1 (mean of 3 measurements):
- Systolic blood pressure >160 mmHg.
Show all 22Show fewer
- Diastolic blood pressure >100 mmHg.
- Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG.
- Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis results,
- Known or suspected history of drug abuse as judged by the investigator.
- Positive screen for drugs of abuse at screening or admission to the study site prior to the administration of the study intervention.
- Changes to any concomitant medication (initiation, dose change, or cessation) within one month prior to the screening visit.
- Any laboratory values with following deviations at screening (one re-test allowed):
- (a) ALT >3X ULN
- (b) AST >3X ULN
- (c) TBL >ULN or INR ≥1.3
- (d) ALP >1.5X ULN
- (e) eGFR <60 mL/min/1.73 m2 (calculated using CKD Epidemiology Collaboration
- [CKD-EPI] formula) and applying the standard correction factor for African
- American to the (CKD-EPI) by multiplying the GFR estimate by 1.159 and
- confirmed.
- (f) Platelets <150 × 109/L
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Non-randomized, Multiple-dose Study to Assess the Knockdown of Hepatic HSD17B13 mRNA Expression, Pharmacokinetics, Safety, and Tolerability Following Administration of AZD7503 in Participants With Non-alcoholic Fatty Liver Disease
This is a two-part study. In Part A, eligible participants will undergo a baseline diagnostic liver biopsy to determine non-alcoholic fatty liver disease (NAFLD) Activity Score (NAS) and fibrosis stage, but will not receive study intervention. In Part B, participants with histologically confirmed NAFLD or non-alcoholic steatohepatitis (NASH) will receive study intervention.
Read the detailed description
This is a single center, open-label Phase I study to assess knockdown of hepatic HSD17B13 mRNA pharmacokinetics (PK), safety, and tolerability following multiple doses of AZD7503 in male and/or female participants of non-childbearing status with NAFLD or NASH.
In Part A, participants at high risk for NAFLD/NASH meeting inclusion criteria for Part A (Section 5.1) and none of the exclusion criteria noted in Section 5.2 will undergo a diagnostic, baseline liver biopsy per standard clinical care. Participants will be consented for the liver biopsy as a first step to determine eligibility for Part B. In Part B, participants will be consented for study intervention administration and repeat liver biopsy at the end-of-treatment (EOT). Eligible participants will be assigned to 1 study intervention cohort. Two additional cohorts may be added based on data from the FiH study (D9230C00001) and emerging data from this study.
Participants who are selected for Part B based on histopathology evaluation (NAFLD or NASH with NAS of ≥3) will have an assessment of the hepatic HSD17B13 mRNA expression from both the liver biopsy obtained in Part A and the liver biopsy obtained at the end of study intervention administration in Part B. The assessments for hepatic HSD17B13 mRNA expression will be performed after each dose cohort is treated and before moving to the next dose cohort.
- Conditions
- Non-alcoholic Fatty Liver Disease, Fatty Liver, Nonalcoholic, NAFLD, Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, NASH
- Being tested
- AZD7503 Intervention
- Keywords
- NASH, NAFLD
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD7503 InterventionDrug
Part A: Participants will be screened for histologic evidence of NAFLD or NASH and all eligibility criteria in part A prior to enrollment in part B.
Part B: Participants consented to part B will be administered the study drug over the course of 31 days. At the end of the study a liver biopsy will be collected to measure for endpoints.
| Study group | Role | What they receive |
|---|---|---|
| Intervention/ Drug | Experimental | Investigation of the knockdown of hepatic HSD17B13 mRNA expression, PK, safety, and tolerability following multiple dose administration of AZD7503 in male participants and female participants of non-childbearing potential with NAFLD or NASH Receives: Drug: AZD7503 Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with Adverse Events (AEs).
To assess adverse events as a variable of safety and tolerability of AZD7503.
Measured: 99 days
Secondary outcomes (16)
Change in HSD17B13 mRNA Expression
HSD17B13 mRNA expression from baseline to Day 31 will be assessed
Measured: 31 days
Number of participants with positive anti-drug antibodies to AZD7503
To explore the formation of ADAs.
Measured: 99 days
Area under plasma concentration time-curve from zero to infinity (AUCinf) of AZD7503
To characterise the PK (AUCinf) of AZD7503 following SC administration of AZD7503
Measured: 99 days
Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast) of AZD7503
To characterize the PK (AUClast) of AZD7503 following SC administration of AZD7503.
Measured: 99 days
Maximum observed plasma (peak) drug concentration (Cmax) of AZD7503
To characterise the PK (Cmax) of AZD7503 following SC administration of AZD7503.
Measured: 99 days
Time to reach peak or maximum observed concentration or responsefollowing drug administration (tmax) of AZD7503
To characterise the PK (tmax) of AZD7503 following SC administration of AZD7503.
Measured: 99 days
Half-life associated with terminal slope (λz) of a semi logarithmic concentration time curve (t½λz) of AZD7503
To characterise the PK (t½λz) of AZD7503 following SC administration of AZD7503.
Measured: 99 days
Mean residence time of the unchanged drug in the systemic circulation (MRTinf) of AZD7503
To characterise the PK (MRTinf) of AZD7503 following SC administration of AZD7503.
Measured: 99 days
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of AZD7503
To characterise the PK (CL/F) of AZD7503 following SC administration of AZD7503.
Measured: 99 days
Apparent volume of distribution at steady state following extravascular administration based on terminal phase(Vz/F) of AZD7503
To characterise the PK (Vz/F) of AZD7503 following SC administration of AZD7503.
Measured: 99 days
Time of last observed (quantifiable) concentration (tlast) of AZD7503
To characterise the PK (tlast) of AZD7503 following SC administration of AZD7503.
Measured: 99 days
Lowest observed drug concentration (Ctrough) before next dose of AZD7503
To characterise the PK (Ctrough) of AZD7503 following SC administration of AZD7503.
Measured: 99 days
Apparent volume of distribution at steady state following extravascular administration (Vss/F) of AZD7503
To characterise the PK (Vss/F) of AZD7503 following SC administration of AZD7503.
Measured: 99 days
Accumulation ratio for AUC of AZD7503.
To characterize the PK (Rac AUC) of AZD7503 following SC administration of AZD7503
Measured: 99 days
Accumulation ratio for Cmax (Rac Cmax) of AZD7503
To characterize the PK (Rac Cmax) of AZD7503 following SC administration of AZD7503.
Measured: 99 days
Partial area under plasma concentration-time-curve from time 0 to time t (AUC(0-t)) of AZD7503
To characterise the PK (AUC(0-t)) of AZD7503 following SC administration of AZD7503
Measured: 99 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2022
- Study start12 Aug 2022
- Primary completion20 Nov 2023
- Study completion27 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05560607
- Sponsor's protocol ID
- D9230C00003
- Status last verified
- Jul 2025
- First submitted
- 9 Aug 2022
- Last updated
- 20 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request 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.
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Non-randomized, Multiple-dose Study to Assess the Knockdown of Hepatic HSD17B13 mRNA Expression, Pharmacokinetics, Safety, and Tolerability Following Administration of AZD7503 in Participants With Non-alcoholic Fatty Liver Disease
- ClinicalTrials.gov ID
- NCT05560607
- Acronym / sponsor ID
- D9230C00003
- Conditions
- Non-alcoholic Fatty Liver Disease, Fatty Liver, Nonalcoholic, NAFLD, Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, NASH
- Keywords
- NASH, NAFLD
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 12 Aug 2022 (actual)
- Primary completion
- 20 Nov 2023 (actual)
- Study completion
- 27 Feb 2024 (actual)
- First posted
- 29 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a two-part study. In Part A, eligible participants will undergo a baseline diagnostic liver biopsy to determine non-alcoholic fatty liver disease (NAFLD) Activity Score (NAS) and fibrosis stage, but will not receive study intervention. In Part B, participants with histologically confirmed NAFLD or non-alcoholic steatohepatitis (NASH) will receive study intervention.
Detailed description
This is a single center, open-label Phase I study to assess knockdown of hepatic HSD17B13 mRNA pharmacokinetics (PK), safety, and tolerability following multiple doses of AZD7503 in male and/or female participants of non-childbearing status with NAFLD or NASH.
In Part A, participants at high risk for NAFLD/NASH meeting inclusion criteria for Part A (Section 5.1) and none of the exclusion criteria noted in Section 5.2 will undergo a diagnostic, baseline liver biopsy per standard clinical care. Participants will be consented for the liver biopsy as a first step to determine eligibility for Part B. In Part B, participants will be consented for study intervention administration and repeat liver biopsy at the end-of-treatment (EOT). Eligible participants will be assigned to 1 study intervention cohort. Two additional cohorts may be added based on data from the FiH study (D9230C00001) and emerging data from this study.
Participants who are selected for Part B based on histopathology evaluation (NAFLD or NASH with NAS of ≥3) will have an assessment of the hepatic HSD17B13 mRNA expression from both the liver biopsy obtained in Part A and the liver biopsy obtained at the end of study intervention administration in Part B. The assessments for hepatic HSD17B13 mRNA expression will be performed after each dose cohort is treated and before moving to the next dose cohort.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention/ Drug | Experimental | Drug: AZD7503 InterventionInvestigation of the knockdown of hepatic HSD17B13 mRNA expression, PK, safety, and tolerability following multiple dose administration of AZD7503 in male participants and female participants of non-childbearing potential with NAFLD or NASH |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Participant must be ≥ 18 to ≤ 70 years of age at the time of signing the informed consent.
- Participants with suspected or confirmed NAFLD or NASH including laboratory values with any of the following deviations at screening
- Body mass index (BMI) ≥20 kg/m2.
- Male and /or female of non-child bearing potential.
- Histologic evidence of NAFLD or NASH with a NAS ≥3 following baseline liver biopsy.
Key exclusion criteria (22 listed)
- History or presence of hepatic disease (with the exception of hepatic steatosis, NASH) or evidence of other known forms of known chronic liver
- History of liver transplant, evidence of cirrhosis, or current placement on a liver transplant
- Positive results for HIV antigen and hepatitis B surface antigen If a participant has a positive result at the screening visit for hepatitis C antibody, the investigator will document that the participant has hepatitis C RNA below the limit of detection and has not received curative treatment in the last 3 years.
- History of alcohol abuse or excessive intake of alcohol as judged by the investigator.
- Uncontrolled blood pressure, defined as any of the following during pre-screening and/or Day -1 (mean of 3 measurements):
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD7503 InterventionPart A: Participants will be screened for histologic evidence of NAFLD or NASH and all eligibility criteria in part A prior to enrollment in part B. Part B: Participants consented to part B will be administered the study drug over the course of 31 days. At the end of the study a liver biopsy will be collected to measure for endpoints. | Drug | Intervention/ Drug |
Primary outcome
Number of participants with Adverse Events (AEs).
Time frame: 99 days
To assess adverse events as a variable of safety and tolerability of AZD7503.
16 secondary outcomes
Change in HSD17B13 mRNA Expression
Time frame: 31 days
Number of participants with positive anti-drug antibodies to AZD7503
Time frame: 99 days
Area under plasma concentration time-curve from zero to infinity (AUCinf) of AZD7503
Time frame: 99 days
Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast) of AZD7503
Time frame: 99 days
Maximum observed plasma (peak) drug concentration (Cmax) of AZD7503
Time frame: 99 days
Time to reach peak or maximum observed concentration or responsefollowing drug administration (tmax) of AZD7503
Time frame: 99 days
Half-life associated with terminal slope (λz) of a semi logarithmic concentration time curve (t½λz) of AZD7503
Time frame: 99 days
Mean residence time of the unchanged drug in the systemic circulation (MRTinf) of AZD7503
Time frame: 99 days
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of AZD7503
Time frame: 99 days
Apparent volume of distribution at steady state following extravascular administration based on terminal phase(Vz/F) of AZD7503
Time frame: 99 days
Time of last observed (quantifiable) concentration (tlast) of AZD7503
Time frame: 99 days
Lowest observed drug concentration (Ctrough) before next dose of AZD7503
Time frame: 99 days
Apparent volume of distribution at steady state following extravascular administration (Vss/F) of AZD7503
Time frame: 99 days
Accumulation ratio for AUC of AZD7503.
Time frame: 99 days
Accumulation ratio for Cmax (Rac Cmax) of AZD7503
Time frame: 99 days
Partial area under plasma concentration-time-curve from time 0 to time t (AUC(0-t)) of AZD7503
Time frame: 99 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2025.
- d9230c00003-Redacted\_CSR synopsisLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request 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.
Related trials for Non-alcoholic Fatty Liver Disease
Not yet recruiting
Efficacy of Carnitine Complex in Improving Hepatic Steatosis in Potential Liver Donors
Hepatic Steatosis, Fatty Liver
Recruiting
NAFLD Clinical Care Pathway
NAFLD, MASLD
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
RecruitingPhase 1
A Study of Efimosfermin Alfa in Adults With Hepatic Impairment
Non-alcoholic Fatty Liver Disease
RecruitingPhase 2
A Study of Efimosfermin Alfa in Participants With Biopsy-confirmed Cirrhosis (Compensated) Due to MASH
Metabolic Dysfunction-Associated Steatohepatitis, Non-alcoholic Fatty Liver Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD7503 Intervention in people with Non-alcoholic Fatty Liver Disease and Fatty Liver, Nonalcoholic, run by AstraZeneca at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with Adverse Events (AEs). (time frame: 99 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2025.