Dose Exploration Intramuscular/Intravenous Prophylaxis Pharmacokinetic Exposure Response Study
Study Details
Study Description
Brief Summary
This is a dose exploration study to evaluate the safety and pharmacokinetics (PK) of AZD3152 in healthy adult male and female participants, across different dose levels and routes of administration (ie, Intramuscular [IM] injection and Intravenous [IV] infusion).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
The study will be conducted in the United States of America.
Eligible healthy participants will be randomized in a 10:2 ratio to receive either AZD3152 or placebo administered IM or IV, across 4 fixed-dose cohorts. Participants will receive a single dose of AZD3152/placebo.
Cohort 1: Dose X of AZD3152 or placebo, as an IM injection Cohort 2: Dose X of AZD3152 or placebo, administered IV Cohort 3: Dose Y of AZD3152 or placebo, as an IM injection Cohort 4: Dose Y of AZD3152 or placebo, administered IV
The study will comprise of:
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A Screening Period of maximum 28 days.
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A Treatment Period of 1 Day.
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A Follow-up Period of 12 months after study intervention (Day 365).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: AZD3152 Dose X (IM) Participants will receive dose X of AZD3152 on Day 1 as a single IM injection. |
Drug: AZD3152
AZD3152 will be administered via IM injection or IV infusion, as per the assigned arms.
|
| Experimental: AZD3152 Dose X (IV) Participants will receive dose X of AZD3152 on Day 1 as an IV infusion. |
Drug: AZD3152
AZD3152 will be administered via IM injection or IV infusion, as per the assigned arms.
|
| Experimental: AZD3152 Dose Y (IM) Participants will receive dose Y of AZD3152 on Day 1 as 2 sequential IM injections. |
Drug: AZD3152
AZD3152 will be administered via IM injection or IV infusion, as per the assigned arms.
|
| Experimental: AZD3152 Dose Y (IV) Participants will receive dose Y of AZD3152 on Day 1 as an IV infusion. |
Drug: AZD3152
AZD3152 will be administered via IM injection or IV infusion, as per the assigned arms.
|
| Placebo Comparator: Pooled placebo Participant will receive placebo on Day 1 either via IM injection or IV infusion. |
Other: Placebo
Placebo is a matching volume of 0.9% sodium chloride, will be administered via IM injection or IV infusion, as per the assigned arms.
|
Outcome Measures
Primary Outcome Measures
- Number of participants with adverse event [Until Day 91]
Evaluation of the safety of IM or IV administration of AZD3152 will be done.
- Number of participants with serious adverse event [Until Day 365 or early discontinuation visit (EDV [approximately 19 months])]
Evaluation of the safety of IM or IV administration of AZD3152 will be done.
- Number of participants with adverse event of special interest [Until Day 365 or EDV (approximately 19 months)]
Evaluation of the safety of IM or IV administration of AZD3152 will be done.
- Serum concentration of AZD3152 [Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)]
Pharmacokinetics (PK) characterization of AZD3152 in serum after a single IM or IV dose.
- Maximum observed concentration (Cmax) of AZD3152 [Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)]
PK (Cmax) characterization of AZD3152 in serum after a single IM or IV dose.
- Time to reach maximum observed concentration (tmax) of AZD3152 [Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)]
PK (tmax) characterization of AZD3152 in serum after a single IM or IV dose.
- Terminal elimination half-life (t1/2) of AZD3152 [Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)]
PK (t1/2) characterization of AZD3152 in serum after a single IM or IV dose.
- Area under the serum concentration-curve from 0 to the last quantifiable concentration (AUClast) of AZD3152 [Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)]
PK (AUClast) characterization of AZD3152 in serum after a single IM or IV dose.
- Area under concentration-time curve from 0 to infinity (AUCinf) of AZD3152 [Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)]
PK (AUCinf) characterization of AZD3152 in serum after a single IM or IV dose.
- Apparent total body clearance (CL/F) of AZD3152 (IM administration only) [Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)]
PK (CL/F) characterization of AZD3152 in serum after a single IM.
- Apparent volume of distribution based on terminal phase (Vz/F) of AZD3152 (IM administration only) [Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)]
PK (Vz/F) characterization of AZD3152 in serum after a single IM.
- Total body clearance (CL) of AZD3152 (IV administration only) [Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)]
PK (CL) characterization of AZD3152 in serum after a single IV.
- Volume of distribution based on terminal phase (Vz) of AZD3152 (IV administration only) [Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)]
PK (Vz) characterization of AZD3152 in serum after a single IV.
- Volume of distribution at steady state (Vss) of AZD3152 (IV administration only) [Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)]
PK (Vss) characterization of AZD3152 in serum after a single IV.
Secondary Outcome Measures
- Number of participants with anti-drug antibody (ADA) to AZD3152 [Pre-dose, Days 15, 31, 91, 181, and Day 365]
Evaluation of ADA responses to AZD3152.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Healthy male or female participants with no co-morbidities.
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Participants have suitable veins for cannulation or repeated venipuncture.
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Negative SARS-CoV-2 RT-PCR or SARS-CoV-2 rapid antigen test result at Visit 1.
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Body weight ≥ 45 kg and ≤ 110 kg and body mass index ≥ 18 and <30 kg/m2 at Screening.
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Able to complete the Follow-up Period up to Day 365 as required by the protocol.
Exclusion Criteria:
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History of any clinically important disease or disorder.
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Receipt of immunoglobulin (non-COVID related) or blood products within 6 months prior to Day 1.
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Receipt of an AZD7442 monoclonal antibody (mAb) against SARS-CoV-2 within last 15 months before Day 1.
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Receipt of a COVID-19 vaccine within 14 days prior to Visit 1.
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SARS-CoV-2 infection within 1 month prior to Visit 1 (confirmed either by laboratory testing or a rapid test [including at-home testing]).
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Women who are pregnant, lactating, or of childbearing potential and not using a highly effective method of contraception or abstinence from at least 4 weeks prior to study intervention administration and until at least 6 months after study intervention administration.
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Known or suspected congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy,
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Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention. This includes any acute (time-limited) or febrile (temperature ≥ 38.0°C [100.4ºF]) illness/infection on day prior to or day of planned dosing; participants excluded for transient acute illness may be dosed if illness resolves within the Screening Period or may be rescreened once.
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Any abnormal laboratory values as described in protocol.
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Any known HIV or hepatitis B or C infection at Screening.
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History of alcohol or substance abuse that in the opinion of the Investigator might interfere with the trial conduct or completion.
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Known hypersensitivity to AZD3152.
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Previous hypersensitivity or severe adverse reaction following administration of a mAb.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Anniston | Alabama | United States | 36207 |
| 2 | Research Site | Cullman | Alabama | United States | 35055 |
| 3 | Research Site | Scottsdale | Arizona | United States | 85260 |
Sponsors and Collaborators
- AstraZeneca
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D7000C00004