In this first-in-humans dose escalation study, AZD7442 (AZD8895 + AZD1061) will be evaluated for safety, tolerability, pharmacokinetics, and generation of anti-drug antibodies (ADAs). The study is intended to enable future studies of AZD7442's efficacy in preventing and treating COVID-19.
This is a Phase I, first time in human, randomised, double-blind, placebo-controlled, and
dose escalation study.
The study will comprise of:
1. A Screening Period of up to 27 days (Day -28 through Day -2);
2. A Treatment Period during which participants will be resident at the Clinical Unit from
Day -1, 1 day before Investigational Medicinal Product (IMP) administration (on Day 1)
until at least 24 hours after IMP administration, will be discharged on Day 2 after all
safety evaluations have been completed, and
3. A Follow up Period lasting 360 days (through to Day 361) after the IMP dose.
The study will be conducted at a single study centre in United Kingdom.
Combination Product: AZD7442
Participants randomized to AZD7442 will be administered dose 1, each in Cohort 1a (IM) and Cohort 1b (IV). Participants in Cohort 2 and 3 will receive AZD7442 (IV) doses 2 and 3, respectively. Participants in Cohort 4 will receive AZD7442 (IV) dose 4.
Other: Placebo
Participants randomised to placebo will receive the same volume of solution as participants on active treatment.
Inclusion Criteria:
- Written informed consent and any locally required authorisation obtained from the
participant prior to performing any protocol-related procedures, including screening
evaluations.
- Negative SARS-CoV-2 qRT-PCR and/or serology tests prior to randomisation.
- Weight ≥ 50 kg and ≤ 110 kg at screening, including a BMI of ≥ 18.0 to ≤ 30.0 kg/m^2.
- Healthy by medical history, physical examination, and baseline safety laboratory
studies, according to the judgement of the PI.
- Electrocardiogram without clinically significant abnormalities at screening.
- Able to complete the Follow-up Period through Day 361.
- Females of childbearing potential who are sexually active with a non-sterilised male
partner must have used a highly effective method of contraception for at least 28 days
prior to dosing with IMP and must agree to continue using such precautions until the
Final Follow-up Visit. Periodic abstinence, the rhythm method, and the withdrawal
method are not acceptable methods of contraception.
Exclusion Criteria:
- Known hypersensitivity to any component of the IMP.
- History of allergic disease or reactions likely to be exacerbated by any component of
the IMP.
- Previous hypersensitivity, infusion-related reaction or severe adverse reaction
following administration of a mAbs.
- Acute (time-limited) illness, including fever above 37.5°C (99.5 °F), on day prior to
or day of planned dosing; participants excluded for transient acute illness may be
dosed if illness resolves within the 27-day Screening Period or may be rescreened
once.
- Any drug therapy within 7 days prior to Day 1 (except contraceptives or a single use
of acetaminophen, aspirin, antihistamine, or combination over the counter (OTC)
product that contains acetaminophen with an antihistamine, or OTC nonsteroidal
anti-inflammatory agent at a dose equal to or lower than that recommended on the
package). Vitamins and other nutritional supplements that are not newly introduced,
ie, have been taken for at least 30 days prior to enrolment, are not exclusionary.
- Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 2 months
prior to screening.
- Receipt of immunoglobulin or blood products within 6 months prior to screening.
- SARS CoV-2 or COVID-19:
- Participants with any confirmed current or previous COVID-19 infection before
randomisation.
- Participant has clinical signs and symptoms consistent with COVID-19, eg, fever,
dry cough, dyspnoea, sore throat, fatigue or confirmed infection by appropriate
laboratory test within the last 4 weeks prior to screening or on admission.
- Any prior receipt of investigational or licensed vaccine indicated for the
prevention of SARS CoV-2 or COVID-19 or expected receipt during the period of
study follow up.
- Receipt of any IMP in the preceding 90 days or expected receipt of IMP during the
period of study follow-up, or concurrent participation in another interventional
study.
- Previous receipt of a mAb within 6 months, or five antibody half lives (whichever is
longer), prior to study start.
- Immunodeficiency due to illness, including Human immunodeficiency virus (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. HIV testing must be negative at screening.
- Either history of active infection with hepatitis B or C or positive test for
hepatitis C or for hepatitis B surface antigen at screening.
- History of infection with SARS or MERS.
- Aspartate aminotransferase, ALT, or serum creatinine above the ULN; bilirubin and ALP
>1.5 × ULN.
- Haemoglobin or platelet count below the LLN at screening. White blood cell or
neutrophil count outside normal references ranges.
- History of malignancy.
- Any laboratory value in the screening panel that, in the opinion of the PI, is
clinically significant or might confound analysis of study results.
- Pregnant or nursing female.
- History of alcohol or drug abuse within the past 2 years that, according to the PI,
might affect assessments of safety or ability of participant to comply with all study
requirements OR positive urine drug or alcohol screening.
- Any condition that, in the opinion of the PI, might compromise participant safety or
interfere with evaluation of the IMP or interpretation of participant safety or study
results.
- Employees of the sponsor, clinical study site, or any other individuals involved with
the conduct of the study, or immediate family members of such individuals.
- Absence of suitable veins for blood sampling (IM and IV cohorts) and administration of
IMP (IV cohorts).
Research Site
Harrow, United Kingdom
Pablo Forte Soto, MD, MSc, PhD, Principal Investigator
Parexel EPCU (London)