Clinical Trials/NCT06639997

NCT06639997

Completed

Phase 1

A Phase I Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AZD5148 in Healthy Japanese Adults

AstraZeneca1 site in 1 country16 target enrollmentOctober 31, 2024

ConditionsClostridioides Difficile Infection

InterventionsAZD5148 Placebo

Overview

Phase: Phase 1
Intervention: AZD5148
Conditions: Clostridioides Difficile Infection
Sponsor: AstraZeneca
Enrollment: 16
Locations: 1
Primary Endpoint: Number of Japanese participants with adverse events (AEs).
Status: Completed
Last Updated: 3 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to measure safety, tolerability and PK of a single dose of AZD5148 administered via IV bolus or IM injection in healthy Japanese participants.

Detailed Description

The purpose of this study is to measure safety, tolerability and PK of a single dose of AZD5148 administered via IV bolus or IM injection in healthy Japanese participants. Study details include: • There will be 12 planned visits (including screening visit) over a period of up to 56 weeks.

Registry

clinicaltrials.gov

Start Date

October 31, 2024

End Date

December 25, 2025

Last Updated

3 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

AstraZeneca

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Participant must be Japanese male or female and aged 18-65 years inclusive at the time of signing the informed consent.
•Participants who are overtly healthy, as determined by medical evaluation, including medical history, physical examination and baseline safety laboratory studies, according to the judgement of the investigator.
•Electrocardiograms without clinically significant abnormalities at screening.
•Able to complete the Follow-up Period through Day 361 as required by the protocol.
•No medical history of symptomatic C. difficile infection within the prior 2 years.
•Participants must be medically stable, defined as disease not requiring significant change in therapy or hospitalisation or worsening disease during the 1 month prior to enrolment, with no acute change in condition at the time of study enrolment as judged by the Investigator.
•Able to understand and comply with study requirements/procedures based on the assessment of the Investigator.
•Body weight within the range of 45 to 110 kg and body mass index (BMI) within the range of 18.0 to 32.0 kg/m2 (inclusive) at screening.
•Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
•Women of no childbearing potential are defined as women who are either permanently sterilised or postmenopausal. Women will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to the planned date of randomisation without an alternative medical cause. The following age-specific requirements apply:

Exclusion Criteria

•Previous hypersensitivity, infusion-related reaction or severe adverse reaction following mAb administration.
•Abnormal vital signs after 5 minutes of supine rest, at Screening and/or admission to the study site.
•Any clinically important abnormalities in laboratory values at the Screening Visit.
•Clinically significant bleeding disorder or prior history of significant bleeding or bruising following IM injections or venipuncture
•Primary or acquired immunodeficiency, including HIV infection, or due to drugs, including any course of glucocorticoid therapy exceeding 2 weeks of prednisone or equivalent at a dose of 20 mg daily or every other day within 6 months prior to screening. Any known HIV infection at screening
•Any known hepatitis B or C virus infection at screening
•History of malignancy other than treated non-melanoma skin cancers or locally treated cervical cancer in the previous 5 years
•Any laboratory value in the screening panel that, in the opinion of the investigator, is clinically significant or might confound analysis of study results
•Absence of suitable veins for blood sampling and IMP administration
•Receipt of immunoglobulin or blood products, or expected receipt, within 6 months prior to screening or expected to receive during the study

Arms & Interventions

Cohort 1 - AZD5148 IM

Biological: AZD5148 (Cohort 1) ・Single dose of AZD5148 IM

Intervention: AZD5148

Cohort 1 - Placebo IM

Biological: Placebo (Cohort 1) Single dose of Placebo IM

Intervention: Placebo

Cohort 2 - AZD5148 IV

Biological: AZD5148 (Cohort 2) ・Single dose of AZD5148 IV

Intervention: AZD5148

Cohort 2 - Placebo IV

Biological: Placebo (Cohort 2) Single dose of Placebo IV

Intervention: Placebo

Outcomes

Primary Outcomes

Number of Japanese participants with adverse events (AEs).

Time Frame: From Randomization (Day -1 or Day 1) to Day 91

To evaluate the safety and tolerability of AZD5148 administered as a single IV or IM dose to healthy Japanese adult participants.

Number of participants with serious adverse events (SAEs)

Time Frame: From Screening (Day -28 to Day -2) to final Follow-up Visit (Day 361)

To evaluate the safety and tolerability of AZD5148 administered as a single IV or IM dose to healthy Japanese adult participants.

Number of participants with adverse events of special interest (AESIs)

Time Frame: From Randomization (Day -1 or Day 1) to final Follow-up Visit (Day 361)

To evaluate the safety and tolerability of AZD5148 administered as a single IV or IM dose to healthy Japanese adult participants.

Secondary Outcomes

Maximum observed drug concentration (Cmax)(From Day 1 until last Follow up visit (Day 361))
Time to reach maximum observed concentration (tmax)(From Day 1 until last Follow up visit (Day 361 days))
Time of last quantifiable concentration (tlast)(From Day 1 until last Follow up visit (Day 361 days))
Terminal elimination half-life, estimated as (ln2)/λz (t1/2λz)(From Day 1 until last Follow up visit (Day 361 days))
Area under concentration-curve from time 0 to the time of last quantifiable concentration (AUClast)(From Day 1 until last Follow up visit (Day 361 days))
Area under concentration-time curve from time 0 extrapolated to infinity (AUCinf)(From Day 1 until last Follow up visit (Day 361 days))
Volume of distribution at steady state (IV administration only) (Vss)(From Day 1 until last Follow up visit (Day 361 days))
Volume of distribution at terminal phase (IV administration only) (Vz)(From Day 1 until last Follow up visit (Day 361 days))
Systematic clearance (IV administration only) (CL)(From Day 1 until last Follow up visit (Day 361 days))
Apparent total body clearance (IM administration only) (CL/F)(From Day 1 until last Follow up visit (Day 361 days))
Apparent volume of distribution based on the terminal phase (IM administration only) (Vz/F)(From Day 1 until last Follow up visit (Day 361 days))
Bioavailability for extravascular administration (IM administration only) (F)(From Day 1 until last Follow up visit (Day 361 days))
Incidence of positive ADAs against AZD5148 in serum(Day 1 (pre-dose), Day 29, Day 91, Day 181 and Day 361)