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

MedImmune

Status and phase: Completed; Phase 1

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

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01544348

CD-RI-MEDI4212-1085

Details and patient eligibility

About

Phase 1 study to evaluate the safety of MEDI4212.

Full 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).

Enrollment: 295 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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295 participants in 8 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

A single dose of placebo matched to MEDI4212 subcutaneous injection or intravenous infusion on Day 1.

Treatment:

Other: Placebo

Omalizumab

Active Comparator group

Description:

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.

Treatment:

Biological: Omalizumab

MEDI4212 5 mg Subcutaneous

Experimental group

Description:

A single dose of MEDI4212 5 mg injection subcutaneously on Day 1.

Treatment:

Biological: MEDI4212 5 mg Subcutaneous

MEDI4212 15 mg Subcutaneous

Experimental group

Description:

A single dose of MEDI4212 15 mg injection subcutaneously on Day 1.

Treatment:

Biological: MEDI4212 15 mg Subcutaneous

MEDI4212 60 mg Subcutaneous

Experimental group

Description:

A single dose of MEDI4212 60 mg injection subcutaneously on Day 1.

Treatment:

Biological: MEDI4212 60 mg Subcutaneous

MEDI4212 150 mg Subcutaneous

Experimental group

Description:

A single dose of MEDI4212 150 mg injection subcutaneously on Day 1.

Treatment:

Biological: MEDI4212 150 mg Subcutaneous

MEDI4212 300 mg Subcutaneous

Experimental group

Description:

A single dose of MEDI4212 300 mg injection subcutaneously on Day 1.

Treatment:

Biological: MEDI4212 300 mg Subcutaneous

MEDI4212 300 mg Intravenous

Experimental group

Description:

A single dose of MEDI4212 300 mg intravenous infusion over 120 minutes on Day 1.

Treatment:

Biological: MEDI4212 300 mg Intravenous