Phase 1, Randomized, Placebo-controlled, Dose-escalation Safety Study of MEDI4212 in Allergic Subjects (MEDI42121085)

Inclusion Criteria:

1. Age 18 through 60 years
2. Written informed consent and any locally required authorization
3. Body weight 45-150 kg for Cohorts 1-3, 4b, and 5-9. Body weight 45-90 kg for Cohort 4a
4. Females must have been surgically sterilized or postmenopausal
5. Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from Day 1 through Day 85; Both partners to use contraception
6. Sterilized males must be at least 1-year post vasectomy or use a highly effective contraceptive method
7. Healthy as determined by a responsible physician
8. Current diagnosis of allergic rhinitis, allergic asthma, or atopic dermatitis (cohorts 1-6) with a diagnostic IgE of 30 IU/mL at screening. Diagnostic IgE levels are further restricted for subjects enrolling into each cohort, with the following levels required at screening: Cohorts 1 and 2: 30-700 IU/mL; Cohort 3: 30 700 IU/mL (4 subjects), > 700-1,200 IU/mL (4 subjects), and > 1,200 IU/mL (4 subjects); Cohort 4a: 30-500 IU/mL; Cohort 4b: > 700 IU/mL. Cohorts 5 and 6: 30 700 IU/mL (4 subjects per cohort) and > 700 IU/mL (6 subjects per cohort) or Japanese Cohorts 7-9 IgE of ≥ 30 IU/mL
9. Nonsmoker for ≥ 6 months
10. Obselete critieria as no longer require Positive in vitro IgE fluorescence enzyme immunoassay (FEIA) response
11. A forced expiration volume in one second (FEV1) ≥ 80% predicted in subjects with asthma. Non-asthmatic subjects with FEV1 ≥ 80% predicted, or with FEV1 < 80% predicted but who, in the opinion of the investigator, do not have lung disease.
12. Ability and willingness to complete the follow-up period through Day 85 as required by the protocol

Exclusion Criteria:

1. Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results
2. Concurrent enrollment in another clinical study
3. Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals
4. Exposure to an anti-IgE MAb within 12 months prior to screening
5. Positive drug screen at screening or Day -1. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids, and benzodiazepines
6. History of regular alcohol abuse within 12 months prior to screening
7. History of sensitivity to any component of the investigational product formulation or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation

8. Subjects with abnormal liver function test values (aspartate transaminase [AST] and alanine transaminase [ALT]) at screening as defined as follows:

   a) Liver function test values ≥ 1.5 × upper limit of normal (ULN)

9. Unwillingness or inability to follow the procedures outlined in the protocol
10. Positive test or history of hepatitis B or positive hepatitis C
11. Positive test or history of human immunodeficiency virus (HIV) or subject is known to be HIV seropositive
12. History of cancer, with the exception of basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success
13. Women who are pregnant, breastfeeding, or lactating
14. Plans to donate blood during the study period
15. Hyper-IgE syndrome or bronchopulmonary aspergillosis
16. Prior history of Immune Complex Disease or type 3 hypersensitivity reactions to MAb administration
17. Known history of prior infusion reaction to MAb administration
18. History of untreated parasitic/helminthic infection within 6 months prior to screening

19. Uses any of the following medications:

    1. Oral corticosteroids
    2. Medium to high dose ICS/LABA
    3. Immunosuppressives
    4. Beta blockers
20. If receiving allergy immunotherapy, must be on stable dose for 3 months. Must not receive allergy immunotherapy within 7 days of investigational product administration.