AZD7798 Safety, Tolerability, and Pharmacokinetics After a Single Dose Administration to Healthy Subjects
Study Details
Study Description
Brief Summary
This study will assess the safety, tolerability, immunogenicity, and pharmacokinetics (PK), and explore the pharmacodynamics (PD) of single ascending doses of AZD7798 in healthy subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This is a Phase I, First In Human (FIH), randomised, double-blind, placebo controlled, single ascending dose (SAD), sequential group study in healthy male and female subjects performed at a single study centre.
This study will consist of seven cohorts.
Fifty-six healthy subjects (with potential to include up to approximately 64) are planned to participate. Eight subjects will participate in each cohort.
Within each cohort, 6 subjects will be randomised to receive AZD7798 and 2 subjects will be randomised to receive placebo. Dosing for each ascending dose cohort will proceed with 2 subjects in a sentinel cohort such that 1 subject will be randomised to receive placebo and 1 subject will be randomised to receive AZD7798. Each subject will be involved in the study for up to approximately 17 weeks.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1: AZD7798 dose 1 A total of 6 subjects will receive single ascending doses of AZD7798. |
Biological: AZD7798
Subjects will receive AZD7798 as a single or multiple ascending dose.
|
| Experimental: Cohort 2: AZD7798 dose 2 A total of 6 subjects will receive single ascending doses of AZD7798. |
Biological: AZD7798
Subjects will receive AZD7798 as a single or multiple ascending dose.
|
| Experimental: Cohort 3: AZD7798 dose 3 A total of 6 subjects will receive single ascending doses of AZD7798. |
Biological: AZD7798
Subjects will receive AZD7798 as a single or multiple ascending dose.
|
| Experimental: Cohort 4: AZD7798 dose 4 A total of 6 subjects will receive single ascending doses of AZD7798. |
Biological: AZD7798
Subjects will receive AZD7798 as a single or multiple ascending dose.
|
| Experimental: Cohort 5: AZD7798 dose 5 A total of 6 subjects will receive single ascending doses of AZD7798. |
Biological: AZD7798
Subjects will receive AZD7798 as a single or multiple ascending dose.
|
| Experimental: Cohort 6: AZD7798 dose 6 A total of 6 subjects will receive single ascending doses of AZD7798. |
Biological: AZD7798
Subjects will receive AZD7798 as a single or multiple ascending dose.
|
| Experimental: Cohort 7: AZD7798 dose 7 A total of 6 subjects will receive single ascending doses of AZD7798. |
Biological: AZD7798
Subjects will receive AZD7798 as a single or multiple ascending dose.
|
| Experimental: Placebo A total of 2 subjects per cohort will receive placebo. |
Biological: Placebo
Subjects will receive placebo matching the AZD7798 dose as a single or multiple ascending dose.
|
Outcome Measures
Primary Outcome Measures
- Number of participants with Adverse Events (AEs) [Until follow-up (Day 85) or Early termination (ET)]
The safety and tolerability of AZD7798 following administration of single ascending doses will be assessed.
Secondary Outcome Measures
- Area under plasma concentration time curve from zero to infinity (AUCinf) [Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85]
The AUCinf of AZD7798 following administration of single ascending doses will be assessed.
- AUClast [Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85]
The AUClast of AZD7798 following administration of single ascending doses will be assessed.
- Maximum serum concentration (Cmax) [Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85]
The Cmax of AZD7798 following administration of single ascending doses will be assessed.
- Time to reach maximum serum concentration (tmax) [Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85]
The tmax of AZD7798 following administration of single ascending doses will be assessed.
- Time to last measurable concentration (tlast) [Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85]
The tlast of AZD7798 following administration of single ascending doses will be assessed.
- Terminal elimination half-life (t½λz) [Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85]
The t½λz of AZD7798 following administration of single ascending doses will be assessed.
- Systemic clearance (CL) [Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85]
The CL of AZD7798 following administration of single ascending doses will be assessed.
- Apparent total clearance (CL/F) [Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85]
The CL/F of AZD7798 following administration of single ascending doses will be assessed.
- Volume of distribution based on the terminal phase (Vz) [Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85]
The Vz of AZD7798 following administration of single ascending doses will be assessed.
- Apparent volume of distribution based on terminal phase (Vz/F) [Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85]
The Vz/F of AZD7798 following administration of single ascending doses will be assessed.
- Bioavailability (F) [Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85]
The F of AZD7798 following administration of single ascending doses will be assessed.
- Volume of distribution at steady state (Vss) [Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85]
The Vss of AZD7798 following administration of single ascending doses will be assessed.
- AUClast/D [Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85]
The AUClast/D of AZD7798 following administration of single ascending doses will be assessed.
- AUCinf/D [Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85]
The AUCinf/D of AZD7798 following administration of single ascending doses will be assessed.
- Cmax/D [Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85]
The Cmax/D of AZD7798 following administration of single ascending doses will be assessed.
- Percentage of patients with antidrug antibodies (ADAs) [Day 1 to Day 8, and Days 15, 22, 29, 43, 57, and 85]
The immunogenicity of AZD7798 following administration of single ascending doses will be assessed.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Provision of signed and dated, written informed consent prior to any study specific procedures.
-
Healthy male and female (of childbearing and non childbearing potential) subjects aged 18 to 50 years inclusive.
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Have a BMI between 18 and 30 kg/m2 inclusive and weigh at least 45 kg and no more than 100 kg inclusive.
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Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating.
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Evidence of completion of an appropriate vaccination regimen to SARS-CoV-2 at least 14 days prior to screening as appropriate and recommended in contemporaneous local, regional, or national guidelines.
Exclusion Criteria:
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History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study, ie, history of any clinically significant disease suggesting immunodeficiency or abnormal immune function or history or presence of clinically significant gastrointestinal (GI), hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of monoclonal antibodies.
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Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of Investigational Medicinal Product (IMP).
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Selected laboratory values with deviations.
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Any clinically important abnormalities in clinical chemistry, haematology, or urinalysis results.
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Any positive result on Screening for Hepatitis B surface antigen (HBsAg), anti-Hepatitis B core (HBc) antibody, anti-Hepatitis C virus (HCV) antibody, and human immunodeficiency virus (HIV).
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Abnormal vital signs after 5 minutes supine rest at screening and admission.
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Any clinically important abnormalities in rhythm, conduction or morphology of the electrocardiogram (ECG) after 10 minutes resting and any clinically important abnormalities in the 12 lead ECG that may interfere with the interpretation of Corrected QT interval (QTc) interval changes, including abnormal ST T wave morphology, particularly primary lead or left ventricular hypertrophy.
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Known or suspected history of drug abuse in the last 2 years.
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History of alcohol abuse or excessive intake of alcohol within the last 2 years.
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Positive screen for drugs of abuse at Screening or admission to the Clinical Unit or positive screen for alcohol on admission to the Clinical Unit prior to the first administration of the IMP.
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History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or, history of hypersensitivity to drugs with a similar chemical structure or class to AZD7798.
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Excessive intake of caffeine containing drinks or food.
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Plasma donation within 1 month of the Screening Visit or any blood donation/blood loss
500 mL during the 3 months prior to the Screening Visit.
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Has received another new chemical entity within 30 days/5 half-lives of the first administration of IMP in this study.
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Has received another new chemical entity within 3 months of the first administration of IMP in this study.
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Any ongoing or recent minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and, requirements.
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Subjects who cannot communicate reliably with the Investigator.
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Vulnerable subjects.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Harrow | United Kingdom | HA1 3UJ |
Sponsors and Collaborators
- AstraZeneca
- Parexel
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D9690C00001
- 2022-001438-12