Clinical trial NCT04896541: Phase I Double-blind, Placebo-controlled Study of AZD7442
Official title: A Phase I Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD7442 in Healthy Japanese Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: COVID-19
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-05-21
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: Severe acute respiratory coronavirus 2 is a novel coronavirus that appears to have first emerged in China in November 2019 causing cases of atypical pneumonia. Since then, the COVID-19 pandemic has caused major disruption to healthcare systems with significant socioeconomic impacts. As of 22 December 2020, the virus had spread to all corners of the globe, involving 218 countries/regions with over 78.00 million confirmed cases reported and more than 1.71 million associated deaths. As a response to the ongoing pandemic, AstraZeneca is developing mAbs to the SARS-CoV-2 spike protein. The SARS-CoV-2 spike protein contains the virus's receptor binding domain, which enables the virus to bind to receptors on human cells. By targeting this region of the virus's spike protein, antibodies can block the virus's attachment to human cells, and, therefore, are expected to block infection. AZD7442, a combination of 2 of these mAbs (AZD8895 and AZD1061), is being evaluated for administration to treat or prevent COVID-19. There are currently one ongoing Phase I study and two ongoing Phase III studies with AZD7442, in addition to this treatment study.

Randomization of approximately 40 Japanese participants is planned.

Eligibility criteria: Inclusion Criteria:

* Participants must be Japanese men and women and 18 to 55 years of age inclusive, at the time of signing the informed consent.
* Negative results from both SARS-CoV-2 qRT-PCR and serology tests
* Healthy by medical history, physical examination, and safety laboratory tests, according to the judgement of the investigators

Exclusion Criteria:

* Fever above 37.5°C 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.
* History of infection with SARS or MERS
* Any drug therapy within 7 days prior to Day 1

Primary outcomes:
measure: Adverse event and serious adverse event
timeFrame: Up to Day361
measure: Pharmacokinetics - Serum Concentration
timeFrame: Up to Day361
measure: Pharmacokinetics - Maximum Serum Concentration
timeFrame: Up to Day361
measure: Pharmacokinetics - Time to Maximum Serum Concentration
timeFrame: Up to Day361
measure: Pharmacokinetics - Area under the plasma concentration-time curve to the last measurable time point
timeFrame: Up to Day361
measure: Pharmacokinetics - Area under the plasma concentration-time curve extrapolated to infinity
timeFrame: Up to Day361
measure: Pharmacokinetics - extravascular systemic clearance
timeFrame: Up to 361
measure: Pharmacokinetics -bioavailability
timeFrame: Up to Day361
measure: Pharmacokinetics -extravascular terminal phase volume of distribution
timeFrame: Up to Day361
Secondary outcomes:
measure: The serum neutralizing responses against SARS-CoV-2 using Geometric mean fold rise from baseline
timeFrame: Up to Day361
measure: ADA responses to the AZD7442 in serum.
timeFrame: Up to Day361
measure: The serum neutralizing responses against SARS-CoV-2 using Geometric mean titre from baseline
timeFrame: Up to Day361
Other outcomes:
Locations:
city: Fukuoka-shi
country: Japan
facility: Research Site
Study officials:
References:
citation: Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.