Clinical trial NCT05872958: Dose Exploration Intramuscular/Intravenous Prophylaxis Pharmacokinetic Exposure Response Study
Official title: A Phase I, Randomized, Safety and Pharmacokinetics Study of AZD3152 in Healthy Adults (Little DIPPER)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: COVID-19
Keywords: Coronavirus disease 2019 (COVID-19)
Prophylaxis setting
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-05-24
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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).

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 1.
* 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 1.
* Receipt of an EVUSHELD monoclonal antibody (mAb) against SARS-CoV-2 within last 15 months before Day 1.
* Receipt of a COVID-19 vaccine within 14 days prior to Visit 1.
* 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.
* History of alcohol or substance abuse that in the opinion of the Investigator might interfere with the trial conduct or completion.
* Known hypersensitivity to AZD3152.
* Previous hypersensitivity or severe adverse reaction following administration of a mAb.

Primary outcomes:
measure: Number of participants with adverse event
timeFrame: Until Day 91
measure: Number of participants with serious adverse event
timeFrame: Until Day 365 or early discontinuation visit (EDV [approximately 19 months])
measure: Number of participants with adverse event of special interest
timeFrame: Until Day 365 or EDV (approximately 19 months)
measure: Serum concentration of AZD3152
timeFrame: Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
measure: Maximum observed concentration (Cmax) of AZD3152
timeFrame: Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
measure: Time to reach maximum observed concentration (tmax) of AZD3152
timeFrame: Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
measure: Terminal elimination half-life (t1/2) of AZD3152
timeFrame: Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
measure: Area under the serum concentration-curve from 0 to the last quantifiable concentration (AUClast) of AZD3152
timeFrame: Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
measure: Area under concentration-time curve from 0 to infinity (AUCinf) of AZD3152
timeFrame: Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
measure: Apparent total body clearance (CL/F) of AZD3152 (IM administration only)
timeFrame: Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
measure: Apparent volume of distribution based on terminal phase (Vz/F) of AZD3152 (IM administration only)
timeFrame: Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
measure: Total body clearance (CL) of AZD3152 (IV administration only)
timeFrame: Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
measure: Volume of distribution based on terminal phase (Vz) of AZD3152 (IV administration only)
timeFrame: Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
measure: Volume of distribution at steady state (Vss) of AZD3152 (IV administration only)
timeFrame: Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
Secondary outcomes:
measure: Number of participants with anti-drug antibody (ADA) to AZD3152
timeFrame: Pre-dose, Days 15, 31, 91, 181, and Day 365
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Research Site
state: Alabama
city: Cullman
country: United States
facility: Research Site
state: Alabama
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Orlando
country: United States
facility: Research Site
state: Florida
Study officials:
References: