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

NCT ID: NCT01544348

Last Updated: 2014-12-30

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

295 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-01-31

Study Completion Date

2013-06-30

Brief Summary

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Phase 1 study to evaluate the safety of MEDI4212.

Detailed Description

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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).

Conditions

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Allergic Asthma Atopic Dermatitis Allergic Rhinitis Healthy Volunteers

Keywords

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Allergic Atopic Dermatitis MEDI4212

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

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.

Group Type ACTIVE_COMPARATOR

Omalizumab

Intervention Type BIOLOGICAL

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

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

Group Type EXPERIMENTAL

MEDI4212 5 mg Subcutaneous

Intervention Type BIOLOGICAL

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

MEDI4212 15 mg Subcutaneous

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

Group Type EXPERIMENTAL

MEDI4212 15 mg Subcutaneous

Intervention Type BIOLOGICAL

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

MEDI4212 60 mg Subcutaneous

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

Group Type EXPERIMENTAL

MEDI4212 60 mg Subcutaneous

Intervention Type BIOLOGICAL

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

MEDI4212 150 mg Subcutaneous

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

Group Type EXPERIMENTAL

MEDI4212 150 mg Subcutaneous

Intervention Type BIOLOGICAL

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

MEDI4212 300 mg Subcutaneous

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

Group Type EXPERIMENTAL

MEDI4212 300 mg Subcutaneous

Intervention Type BIOLOGICAL

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

MEDI4212 300 mg Intravenous

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

Group Type EXPERIMENTAL

MEDI4212 300 mg Intravenous

Intervention Type BIOLOGICAL

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

Interventions

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Placebo

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

Intervention Type OTHER

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.

Intervention Type BIOLOGICAL

MEDI4212 5 mg Subcutaneous

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

Intervention Type BIOLOGICAL

MEDI4212 15 mg Subcutaneous

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

Intervention Type BIOLOGICAL

MEDI4212 60 mg Subcutaneous

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

Intervention Type BIOLOGICAL

MEDI4212 150 mg Subcutaneous

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

Intervention Type BIOLOGICAL

MEDI4212 300 mg Subcutaneous

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

Intervention Type BIOLOGICAL

MEDI4212 300 mg Intravenous

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

Intervention Type BIOLOGICAL

Other Intervention Names

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Xolair

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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MedImmune LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Cypress, California, United States

Site Status

Research Site

Glendale, California, United States

Site Status

Research Site

Denver, Colorado, United States

Site Status

Research Site

Miami, Florida, United States

Site Status

Research Site

Baltimore, Maryland, United States

Site Status

Research Site

Pittsburgh, Pennsylvania, United States

Site Status

Research Site

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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Sheldon E, Schwickart M, Li J, Kim K, Crouch S, Parveen S, Kell C, Birrell C. Pharmacokinetics, Pharmacodynamics, and Safety of MEDI4212, an Anti-IgE Monoclonal Antibody, in Subjects with Atopy: A Phase I Study. Adv Ther. 2016 Feb;33(2):225-51. doi: 10.1007/s12325-016-0287-8. Epub 2016 Feb 3.

Reference Type DERIVED
PMID: 26843086 (View on PubMed)

Other Identifiers

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CD-RI-MEDI4212-1085

Identifier Type: -

Identifier Source: org_study_id