臨床研究等提出・公開システム

AZD7442 mAbs are being evaluated for administration to prevent or treat COVID-19. This Phase I study will gather important information on the safety and tolerability of AZD7442.

A Phase I Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD7442 in Healthy Japanese Participants

40

All 40 randomized participants received either AZD7442 or placebo and completed the study. The mean age was 32.2 and 41.3 years for the AZD7442 and pooled placebo groups, respectively. The mean body mass index was 22.4 kg/m2 for the AZD7442 cohorts and 23.1 kg/m2 for the pooled placebo group. The demographic except for age and sex, and the key participant characteristic data were generally balanced between total AZD7442 treatment group and the pooled placebo group.

A total of 6, 6, 12 and 6 participants were randomised to AZD7442 in Cohort 1, Cohort 2, Cohort 3 (sub-cohort 3F and sub-cohort 3M: 6 participants each) and Cohort 4, respectively, and 10 participants were randomised to placebo.All 40 randomised participants received the IP and completed this study.

The safety and tolerability data over the study period (361 days) of AZD7442 300 mg IM, 600 mg IM, 300 mg IV and 1000 mg IV administration did not raise any safety concerns in healthy Japanese participants. Throughout study period, a total of 12/30 (40.0%) participants receiving AZD7442 reported at least one AE. - Cohort 1 (AZD7442 300 mg IM) 2/6 (33.3%) participants reported 3 AEs. - Cohort 2 (AZD7442 600 mg IM) 3/6 (50.0%) participants reported 6 AEs. - Cohort 3 (AZD7442 300 mg IV) 6/12 (50.0%) participants reported 13 AEs. - Cohort 4 (AZD7442 1000 mg IV) 1/6 (16.7%) participants reported 3 AEs. - In total, 3/10 (30.0%) participants in the pooled placebo group reported 4 AEs. All AEs were either mild or moderate in intensity, and there were no AEs of severe intensity. Only headache in the 300 mg IM cohort was considered by the investigator to have a reasonable possibility of a causal relationship with study treatment. There were no deaths, SAEs, or AEs leading to discontinuation of IP in any participant. During the study, 4 participants who received AZD7442 were reported to have contracted COVID-19, and all of them showed mild COVID-19 symptoms. Overall, no clinically important AEs were observed in the study, and none of the AEs across the treatment groups were dose dependent. There were no clinically important abnormalities in clinical laboratory tests, vital signs, electrocardiogram (ECG), physical examination and injection site reaction.

- Adverse Events Refer to 'adverse events'. - Pharmacokinetics of AZD7442 (tixagevimab and cilgavimab) in serum Mean half-lives calculated for both antibodies from all cohorts ranged from 82.05 to 95.91 days for tixagevimab and 77.8 to 92.03 days for cilgavimab and were generally similar for both routes of administration (IM and IV) and all doses.

- The safety and tolerability data over the study period (361 days) of AZD7442 300 mg IM, 600 mg IM, 300 mg IV and 1000 mg IV administration did not raise any safety concerns in healthy Japanese participants. - Overall, the PK analysis supports that the PK of AZD8895 and AZD1061 were similar and that these 2 antibodies followed linear kinetics. - ADA incidence was 6.7% (2 out of 30 participants), with no effect on the serum concentration of either AZD8895 or AZD1061.

Aug. 28, 2023

July. 29, 2023

https://www.sciencedirect.com/science/article/pii/S1341321X23001812?via%3Dihub

Yes

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

https://jrct.mhlw.go.jp/latest-detail/jRCT2071200111

Hibi Kazushige

Astrazeneka K.K

3-1, Ofuka-cho, Kita-ku, Osaka-shi, Osaka

RD-clinical-information-Japan@astrazeneca.com

Hibi Kazushige

Astrazeneka K.K

3-1, Ofuka-cho, Kita-ku, Osaka-shi, Osaka

+81-6-4802-3533

RD-clinical-information-Japan@astrazeneca.com

Complete

Mar. 16, 2021

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

other

1. Participants must be Japanese men and women and 18 to 55 years of age inclusive, at the time of signing the informed consent.

2. Negative results from both SARS-CoV-2 qRT-PCR and serology tests

3. Healthy by medical history, physical examination, and safety laboratory tests, according to the judgement of the investigators

1. Fever above 37.5 degrees Celsius by the time when the participant is randomised; a participant excluded for transient acute illness may be dosed if the illness resolves by the time of randomisation.

2. History of infection with SARS or MERS

3. Any drug therapy within 7 days prior to Day 1

Both

COVID-19

Approximately 40 participants will be randomized in a 6:2 ratio. Arm 1 (n=approximately 30) will receive AZD7442.Arm 2 (n=approximately 10) will receive saline placebo.
Cohort1: IM_ AZD 7442 300mg , Cohort2 IM_AZD7442600mg , Cohort3 IV_ AZD7442 300mg , Cohort4_IV AZD7442 1000mg

1. adverse event
adverse events, concomitant therapy, safety laboratory parameters (haematology, clinical chemistry, coagulation, and urinalysis); 12-lead ECG; vital signs, and physical examination.
[Time Frame: To evaluate the safety and tolerability of AZD7442 administered IV or IM to healthy participants 18 to 55 years of age.]

2. Pharmacokinetics
After IV infusion: Ceoi, Cmax, Tmax, t1/2 z, AUClast, AUCinf, Vss, Vz and CL. After IM injection: Cmax, Tmax, t1/2 z, AUClast, AUCinf, extravascular systemic clearance (CL/F), bioavailability (F) and extravascular terminal phase volume of distribution (Vz/F).
[Time Frame: To evaluate Pharmacokinetics of AZD8895 and AZD1061 after single IV/IM administration of AZD7442.]

+81-92-283-7701

Feb. 28, 2021

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