A Phase I, Randomized, Safety and Pharmacokinetics Study of AZD3152 in Healthy Adults (Little DIPPER)
Overview
- Phase
- Phase 1
- Intervention
- AZD3152
- Conditions
- COVID-19
- Sponsor
- AstraZeneca
- Enrollment
- 98
- Locations
- 1
- Primary Endpoint
- Terminal elimination half-life (t1/2) of AZD3152
- Status
- Completed
- Last Updated
- 11 months ago
Overview
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).
Detailed Description
The study will be conducted in the United States of America. Eligible healthy participants will be randomized to receive either AZD3152 or placebo administered IM or IV, across 5 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 Cohort 5: Dose Z of AZD3152 or placebo, administered IV The study will comprise of: * A Screening Period of maximum 28 days. * A Treatment Period of one Day. * A Follow-up Period of 12 months after study intervention (Day 365).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy male or female participants.
- •Participants have suitable veins for cannulation or repeated venipuncture.
- •Negative SARS-CoV-2 RT-PCR or SARS-CoV-2 rapid antigen test result at Visit
- •Body weight ≥ 45 kg and ≤ 110 kg and body mass index ≥ 18 and \<32 kg/m2 at Screening.
- •Able to complete the Follow-up Period up to Day 365 as required by the protocol.
Exclusion Criteria
- •History of any clinically important disease or disorder.
- •Receipt of any immunoglobulin (either COVID-19 or non-COVID related) or blood products within 6 months prior to Day
- •Receipt of an EVUSHELD monoclonal antibody (mAb) against SARS-CoV-2 within last 15 months before Day
- •Receipt of a COVID-19 vaccine within 14 days prior to Visit
- •SARS-CoV-2 infection within one month prior to Visit 1 (confirmed either by laboratory testing or a rapid test \[including at-home testing\]).
- •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.
- •Known or suspected congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy,
- •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.
- •Any abnormal laboratory values as described in protocol.
- •Any known HIV or hepatitis B or C infection at Screening.
Arms & Interventions
AZD3152 Dose X (IV)
Participants will receive dose X of AZD3152 on Day 1 as an IV infusion.
Intervention: AZD3152
AZD3152 Dose Y (IM)
Participants will receive dose Y of AZD3152 on Day 1 as 2 sequential IM injections.
Intervention: AZD3152
AZD3152 Dose X (IM)
Participants will receive dose X of AZD3152 on Day 1 as a single IM injection.
Intervention: AZD3152
AZD3152 Dose Y (IV)
Participants will receive dose Y of AZD3152 on Day 1 as an IV infusion.
Intervention: AZD3152
AZD3152 Dose Z (IV)
Participants will receive dose Z of AZD3152 on Day 1 as an IV infusion.
Intervention: AZD3152
Pooled placebo
Participant will receive placebo on Day 1 either via IM injection or IV infusion.
Intervention: Placebo
Outcomes
Primary Outcomes
Terminal elimination half-life (t1/2) of AZD3152
Time Frame: 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.
Apparent volume of distribution based on terminal phase (Vz/F) of AZD3152 (IM administration only)
Time Frame: 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.
Number of participants with serious adverse event
Time Frame: 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.
Area under concentration-time curve from 0 to infinity (AUCinf) of AZD3152
Time Frame: 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.
Number of participants with adverse event
Time Frame: Until Day 91
Evaluation of the safety of IM or IV administration of AZD3152 will be done.
Time to reach maximum observed concentration (tmax) of AZD3152
Time Frame: 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.
Area under the serum concentration-curve from 0 to the last quantifiable concentration (AUClast) of AZD3152
Time Frame: 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.
Apparent total body clearance (CL/F) of AZD3152 (IM administration only)
Time Frame: 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.
Total body clearance (CL) of AZD3152 (IV administration only)
Time Frame: 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 at steady state (Vss) of AZD3152 (IV administration only)
Time Frame: Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
PK (Vss) characterization of AZD3152 in serum after a single IV.
Number of participants with adverse event of special interest
Time Frame: 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
Time Frame: 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
Time Frame: 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.
Volume of distribution based on terminal phase (Vz) of AZD3152 (IV administration only)
Time Frame: Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
PK (Vz) characterization of AZD3152 in serum after a single IV.
Secondary Outcomes
- Number of participants with anti-drug antibody (ADA) to AZD3152(Pre-dose, Days 15, 31, 91, 181, and Day 365)