a phase 1, randomized, placebo-controlled, dose-escalation safety study of medi4212 in subjects with ige >= 30 iu/ml

Conditions: Allergic Asthma; Atopic Dermatitis; Allergic Rhinitis; Healthy Volunteers

Summary: phase 1 study to evaluate the safety of medi4212.

a phase 1, randomized, placebo-controlled, dose-escalation study to evaluate the safety and tolerability of ascending single subcutaneous and intravenous doses of medi4212 in subjects with immunoglobulin e (ige) greater than or equal to (\>=) 30 international units per milliliters (iu/ml).

Eligibility criteria:
inclusion criteria: * age 18 through 60 years * written informed consent and any locally required authorization * body weight 45-150 kilogram (kg) for cohorts 1-3, 4b, and 5-9. body weight 45-90 kg for cohort 4a * females must have been surgically sterilized or postmenopausal * non-sterilized 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 * sterilized males must be at least 1-year post vasectomy or use a highly effective contraceptive method * healthy japanese population as determined by a responsible physician * current diagnosis of allergic rhinitis, allergic asthma, or atopic dermatitis (cohorts 1-6) with a diagnostic immunoglobulin e (ige) of 30 international units per milliliter (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), greater than (\>) 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: greater than or equal to (\>=) 30 iu/ml * nonsmoker for \>=6 months * obsolete criteria as no longer require positive in vitro ige fluorescence enzyme immunoassay (feia) response * a forced expiration volume in one second (fev1) \>= 80 percent (%) predicted in subjects with asthma. non-asthmatic subjects with fev1 \>=80% predicted, or with fev1 less than (\<) 80% predicted but who, in the opinion of the investigator, do not have lung disease * ability and willingness to complete the follow-up period through day 85 as required by the protocol. exclusion criteria: * 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 * concurrent enrollment in another clinical study * employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals * exposure to an anti-ige monoclonal antibodies (mab) within 12 months prior to screening * 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 * history of regular alcohol abuse within 12 months prior to screening * 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 * 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 times upper limit of normal (uln) * unwillingness or inability to follow the procedures outlined in the protocol * positive test or history of hepatitis b or positive hepatitis c * positive test or history of human immunodeficiency virus (hiv) or subject is known to be hiv seropositive * history of cancer, with the exception of basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success * women who are pregnant, breastfeeding, or lactating * plans to donate blood during the study period * hyper-ige syndrome or bronchopulmonary aspergillosis * prior history of immune complex disease or type 3 hypersensitivity reactions to mab administration * known history of prior infusion reaction to mab administration * history of untreated parasitic/helminthic infection within 6 months prior to screening * uses any of the following medications: a) oral corticosteroids b) medium to high dose immunocorticosteroids (ics)/ long-acting beta agonists (laba) c) immunosuppressives d) beta blockers * if receiving allergy immunotherapy, must be on stable dose for 3 months. must not receive allergy immunotherapy within 7 days of investigational product administration.

Keywords: allergic atopic dermatitis medi4212