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

Study identifier:CD-RI-MEDI4212-1085

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

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

Medical condition

Allergic Asthma, Healthy Volunteers

Phase

Phase 1

Healthy volunteers

Yes

Study drug

Sex

All

Actual Enrollment

295

Study type

Interventional

Age

18 Years - 60 Years

Date

Study Start Date: 01 Jan 2012

Primary Completion Date: 01 Jun 2013

Study Completion Date: 01 Jun 2013

Study design

Allocation: Randomized
Endpoint Classification: Safety
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Dec 2014 by MedImmune, LLC

Collaborators

Inclusion and exclusion 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.

No locations available

Arms	Assigned Interventions
Placebo Comparator: Placebo A single dose of placebo matched to MEDI4212 subcutaneous injection or intravenous infusion on Day 1.	Other: Placebo A single dose of placebo matched to MEDI4212 subcutaneous injection or intravenous infusion on Day 1.
Active Comparator: 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.	Biological/Vaccine: 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. Other Name: Xolair
Experimental: MEDI4212 5 mg Subcutaneous A single dose of MEDI4212 5 mg injection subcutaneously on Day 1.	Biological/Vaccine: MEDI4212 5 mg Subcutaneous A single dose of MEDI4212 5 mg injection subcutaneously on Day 1.
Experimental: MEDI4212 15 mg Subcutaneous A single dose of MEDI4212 15 mg injection subcutaneously on Day 1.	Biological/Vaccine: MEDI4212 15 mg Subcutaneous A single dose of MEDI4212 15 mg injection subcutaneously on Day 1.
Experimental: MEDI4212 60 mg Subcutaneous A single dose of MEDI4212 60 mg injection subcutaneously on Day 1.	Biological/Vaccine: MEDI4212 60 mg Subcutaneous A single dose of MEDI4212 60 mg injection subcutaneously on Day 1.
Experimental: MEDI4212 150 mg Subcutaneous A single dose of MEDI4212 150 mg injection subcutaneously on Day 1.	Biological/Vaccine: MEDI4212 150 mg Subcutaneous A single dose of MEDI4212 150 mg injection subcutaneously on Day 1.
Experimental: MEDI4212 300 mg Subcutaneous A single dose of MEDI4212 300 mg injection subcutaneously on Day 1.	Biological/Vaccine: MEDI4212 300 mg Subcutaneous A single dose of MEDI4212 300 mg injection subcutaneously on Day 1.
Experimental: MEDI4212 300 mg Intravenous A single dose of MEDI4212 300 mg intravenous infusion over 120 minutes on Day 1.	Biological/Vaccine: MEDI4212 300 mg Intravenous A single dose of MEDI4212 300 mg intravenous infusion over 120 minutes on Day 1.

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Contact Backup

Sarah Crouch