Dose Exploration Intramuscular/Intravenous Prophylaxis Pharmacokinetic Exposure Response Study

A Phase I, Randomized, Safety and Pharmacokinetics Study of AZD3152 in Healthy Adults (Little DIPPER)

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).

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: AZD3152; Other: Placebo

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).

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Research Site
    • Cullman, Alabama, United States, 35055
      • Research Site
  • Arizona
    • Scottsdale, Arizona, United States, 85260
      • Research Site
  • Florida
    • Orlando, Florida, United States, 32819
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / 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.
Experimental: AZD3152 Dose Z (IV); Participants will receive dose Z 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse event	Evaluation of the safety of IM or IV administration of AZD3152 will be done.	Until Day 91
Number of participants with serious adverse event	Evaluation of the safety of IM or IV administration of AZD3152 will be done.	Until Day 365 or early discontinuation visit (EDV [approximately 19 months])
Number of participants with adverse event of special interest	Evaluation of the safety of IM or IV administration of AZD3152 will be done.	Until Day 365 or EDV (approximately 19 months)
Serum concentration of AZD3152	Pharmacokinetics (PK) characterization of AZD3152 in serum after a single IM or IV dose.	Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
Maximum observed concentration (Cmax) of AZD3152	PK (Cmax) characterization of AZD3152 in serum after a single IM or IV dose.	Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
Time to reach maximum observed concentration (tmax) of AZD3152	PK (tmax) characterization of AZD3152 in serum after a single IM or IV dose.	Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
Terminal elimination half-life (t1/2) of AZD3152	PK (t1/2) characterization of AZD3152 in serum after a single IM or IV dose.	Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
Area under the serum concentration-curve from 0 to the last quantifiable concentration (AUClast) of AZD3152	PK (AUClast) characterization of AZD3152 in serum after a single IM or IV dose.	Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
Area under concentration-time curve from 0 to infinity (AUCinf) of AZD3152	PK (AUCinf) characterization of AZD3152 in serum after a single IM or IV dose.	Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
Apparent total body clearance (CL/F) of AZD3152 (IM administration only)	PK (CL/F) characterization of AZD3152 in serum after a single IM.	Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
Apparent volume of distribution based on terminal phase (Vz/F) of AZD3152 (IM administration only)	PK (Vz/F) characterization of AZD3152 in serum after a single IM.	Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
Total body clearance (CL) of AZD3152 (IV administration only)	PK (CL) characterization of AZD3152 in serum after a single IV.	Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
Volume of distribution based on terminal phase (Vz) of AZD3152 (IV administration only)	PK (Vz) characterization of AZD3152 in serum after a single IV.	Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)
Volume of distribution at steady state (Vss) of AZD3152 (IV administration only)	PK (Vss) characterization of AZD3152 in serum after a single IV.	Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with anti-drug antibody (ADA) to AZD3152	Evaluation of ADA responses to AZD3152.	Pre-dose, Days 15, 31, 91, 181, and Day 365

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2023
• Primary Completion (Estimated): August 9, 2024
• Study Completion (Estimated): August 9, 2024

Study Registration Dates

• First Submitted: May 15, 2023
• First Submitted That Met QC Criteria: May 15, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Coronavirus disease 2019 (COVID-19); Prophylaxis setting
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: D7000C00004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests 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.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No