A Phase I Double-blind, Placebo-controlled Study to Evaluate theSafety, Tolerability and Pharmacokinetics of AZD5148 in HealthyJapanese Adults

JRCT ID: jRCT2071240071

Registered date:18/10/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Clostridioides difficile Infection
• Date of first enrollment: 30/10/2024
• Target sample size: 16
• Study type: Interventional
• Intervention(s): Healthy participants will be randomised in each cohort to either AZD5148 or placebo administered IM or IV, across 2 dose cohorts.

Outcome(s)

• Primary Outcome: To evaluate the safety and tolerability of AZD5148 administered as a single IV or IM dose to healthy Japanese adult participants 18 to 65 years of age

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 65age old
• Gender: Both

Include criteria

- Participant must be Japanese male or female and aged 18-65years inclusive at the time of signing the informed consent.

- Participants who are overtly healthy, as determined by medicalevaluation, including medical history, physical examination andbaseline safety laboratory studies, according to the judgement of theinvestigator.

- Electrocardiograms without clinically significant abnormalities atscreening.

- Able to complete the Follow-up Period through Day 361 as requiredby the protocol

- No medical history of symptomatic C. difficile infection within theprior 2 years.

- Participants must be medically stable, defined as disease notrequiring significant change in therapy or hospitalisation orworsening disease during the 1 month prior to enrolment, with noacute change in condition at the time of study enrolment as judgedby the Investigator.

- Able to understand and comply with studyrequirements/procedures based on the assessment of theInvestigator.

- 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 localregulations regarding the methods of contraception for thoseparticipating in clinical studies.

(a) Women of no childbearing potential are defined as women whoare either permanently sterilised or postmenopausal. Women will beconsidered postmenopausal if they have been amenorrhoeic for 12months prior to the planned date of randomisation without analternative medical cause. The following age-specific requirementsapply:

_ Women < 50 years old would be considered postmenopausal if theyhave been amenorrhoeic for 12 months or more following thecessation of exogenous hormonal treatment and follicle-stimulatinghormone levels in the postmenopausal range.

_ Women 50 years old or more would be considered postmenopausal if theyhave been amenorrhoeic for 12 months or more following thecessation of all exogenous hormonal treatment.

(b) Female participants of childbearing potential must use one highlyeffective form of birth control. A highly effective method ofcontraception is defined as one that can achieve a failure rate of lessthan 1% per year when used consistently and correctly. Women ofchildbearing potential who are sexually active with a non-sterilisedmale partner must agree to use one highly effective method of birthcontrol from 3 months prior to IMP administration and agree tocontinue through 360 days following IMP administration. Cessation ofcontraception after this point should be discussed with a responsiblephysician. Periodic abstinence, withdrawal, spermicides only andlactational amenorrhoea method are not acceptable methods ofcontraception. Female condom and male condom should not be usedtogether. All women of childbearing potential must have negativeresults of pregnancy tests prior to dosing.

- Capable of giving signed informed consent which includescompliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclude criteria

- Previous hypersensitivity, infusion-related reaction or severeadverse reaction following mAb administration.

- Abnormal vital signs after 5 minutes of supine rest, at Screeningand/or admission to the study site.

- Any clinically important abnormalities in laboratory values at theScreening Visit.

- Clinically significant bleeding disorder or prior history of significantbleeding or bruising following IM injections or venipuncture- Primary or acquired immunodeficiency, including HIV infection, ordue to drugs, including any course of glucocorticoid therapy exceeding 2 weeks of prednisone or equivalent at a dose of 20 mgdaily or every other day within 6 months prior to screening. Anyknown HIV infection at screening

- Any known hepatitis B or C virus infection at screening

- History of malignancy other than treated non-melanoma skincancers or locally treated cervical cancer in the previous 5 years

- Any laboratory value in the screening panel that, in the opinion ofthe investigator, is clinically significant or might confound analysis ofstudy results

- Absence of suitable veins for blood sampling and IMPadministration

- Receipt of immunoglobulin or blood products, or expected receipt,within 6 months prior to screening or expected to receive during thestudy

- Previous receipt of an mAb within 6 months or five antibody half-lives (whichever is longer), prior to informed consent date

- Receipt of any investigational products in the preceding 90 days orexpected receipt of investigational product during the period ofstudy follow-up or concurrent participation in another interventionalstudy

- Participants with a known hypersensitivity to any component of theIMP

- History of allergic disease or reactions likely to be exacerbated byany component of the IMP

- Blood drawn in excess of a total of 400 mL (1 unit) for any reasonwithin 3 months prior to screening or plan to donate blood until theend of follow-up period

- History of alcohol or drug abuse within the past 2 years that,according to the investigator, might affect the assessments of safetyor ability the of participant to comply with all study requirements

- Deprived of freedom by an administrative or court order, in anemergency setting or hospitalisedinvolu ntarily

- Any condition that, in the opinion of the investigator, mightcompromise participant safety or interfere with the evaluation of theIMP or interpretation of participant safety or study results. Theinvestigator should follow the standard vital sign ranges

- Judgement by the investigator that the participant should notparticipate in the study if the participant is unlikely to comply withstudy procedures, restriction sand requirements.

- Previous randomisation in the present study.

- For females only - currently pregnant or breast-feeding.

- Employees of the sponsor, study site or any other individualsinvolved with the conduct of the study or immediate family membersof such individuals.

Related Information

• Primary Sponsor: Ageishi Yuji
• Secondary ID(s): NCT06639997