A Phase 1, Randomized, Placebo-controlled, Dose-escalation Safety Study of MEDI4212 in Subjects With IgE >= 30 IU/mL

Phase 1

Completed

Conditions: Allergic Asthma
Atopic Dermatitis
Allergic Rhinitis
Healthy Volunteers

Interventions: Biological: MEDI4212 15 mg Subcutaneous
Biological: MEDI4212 150 mg Subcutaneous
Biological: MEDI4212 300 mg Subcutaneous
Biological: MEDI4212 300 mg Intravenous
Other: Placebo
Biological: Omalizumab
Biological: MEDI4212 5 mg Subcutaneous
Biological: MEDI4212 60 mg Subcutaneous

Registration Number: NCT01544348

Lead Sponsor: MedImmune LLC

Brief Summary: Phase 1 study to evaluate the safety of MEDI4212.

Detailed Description: 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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 295

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MEDI4212 15 mg Subcutaneous	MEDI4212 15 mg Subcutaneous	A single dose of MEDI4212 15 mg injection subcutaneously on Day 1.
MEDI4212 150 mg Subcutaneous	MEDI4212 150 mg Subcutaneous	A single dose of MEDI4212 150 mg injection subcutaneously on Day 1.
MEDI4212 300 mg Subcutaneous	MEDI4212 300 mg Subcutaneous	A single dose of MEDI4212 300 mg injection subcutaneously on Day 1.
MEDI4212 300 mg Intravenous	MEDI4212 300 mg Intravenous	A single dose of MEDI4212 300 mg intravenous infusion over 120 minutes on Day 1.
Placebo	Placebo	A single dose of placebo matched to MEDI4212 subcutaneous injection or intravenous infusion on Day 1.
Omalizumab	Omalizumab	A single flexible dose of omalizumab between 150 to 375 milligram (mg) injection based upon participant's Immunoglobulin E (IgE) levels and body weight subcutaneously on Day 1.
MEDI4212 5 mg Subcutaneous	MEDI4212 5 mg Subcutaneous	A single dose of MEDI4212 5 mg injection subcutaneously on Day 1.
MEDI4212 60 mg Subcutaneous	MEDI4212 60 mg Subcutaneous	A single dose of MEDI4212 60 mg injection subcutaneously on Day 1.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	Day 1 to 85	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and up to Day 85 that were absent before treatment or that worsened relative to pre-treatment state.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Exhibiting Anti-Drug Antibodies for MEDI4212 at Any Visit	Days 1 (pre-dose), 15, 43, and 85	Anti-drug antibodies for MEDI4212 were analyzed for participants who received placebo or MEDI4212 as per planned analysis.
Observed Serum Concentration	Pre-dose and post-dose on Day 1; Day 2, 3, 5, 8, 15, 22, 29, 43, 57 and 85	Serum concentration of omalizumab and MEDI4212 were measured for participants who received omalizumab and MEDI4212, respectively.
Free Immunoglobulin E (IgE) Serum Concentration	Day -28 (Screening), -1, 1 (pre-dose), 2, 3, 5, 8, 15, 22, 29, 43, 57, and 85 for all groups; 2 hours post-dose on Day 1 for MEDI4212 300 mg Intravenous group only