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

A Phase 1, Randomized, Placebo-controlled, Dose-escalation Study to Evaluate the Safety of
MEDI4212 in Allergic Subjects

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.