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

Sponsor
MedImmune LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01544348
Collaborator
(none)
295
Enrollment
7
Locations
8
Arms
17
Duration (Months)
42.1
Patients Per Site
2.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Phase 1 study to evaluate the safety of MEDI4212.

Condition or Disease Intervention/Treatment Phase
  • Other: Placebo
  • Biological: Omalizumab
  • Biological: MEDI4212 5 mg Subcutaneous
  • Biological: MEDI4212 15 mg Subcutaneous
  • Biological: MEDI4212 60 mg Subcutaneous
  • Biological: MEDI4212 150 mg Subcutaneous
  • Biological: MEDI4212 300 mg Subcutaneous
  • Biological: MEDI4212 300 mg Intravenous
 Phase 1

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).

Study Design

Study Type:
Interventional
Actual Enrollment :
295 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Randomized, Placebo-controlled, Dose-escalation Study to Evaluate the Safety of MEDI4212 in Subjects With IgE >= 30 IU/mL
Study Start Date :
Jan 1, 2012
Actual Primary Completion Date :
Jun 1, 2013
Actual Study Completion Date :
Jun 1, 2013

Arms and Interventions

Arm Intervention/Treatment
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: 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 Names:
  • Xolair

    		•
    Experimental: MEDI4212 5 mg Subcutaneous

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

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

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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.

    3. 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]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Cypress California United States
    2 Research Site Glendale California United States
    3 Research Site Denver Colorado United States
    4 Research Site Miami Florida United States
    5 Research Site Baltimore Maryland United States
    6 Research Site Pittsburgh Pennsylvania United States
    7 Research Site Madison Wisconsin United States

    Sponsors and Collaborators

    • MedImmune LLC

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    MedImmune LLC
    ClinicalTrials.gov Identifier:
    NCT01544348
    Other Study ID Numbers:
    • CD-RI-MEDI4212-1085
    First Posted:
    Mar 5, 2012
    Last Update Posted:
    Dec 30, 2014
    Last Verified:
    Dec 1, 2014
    Keywords provided by MedImmune LLC
    Allergic
    Atopic Dermatitis
    MEDI4212
    Additional relevant MeSH terms:
    Rhinitis
    Rhinitis, Allergic
    Dermatitis, Atopic
    Dermatitis
    Eczema
    Omalizumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail A total of 295 participants were screened, out of which 209 were screen failures and 86 were randomized.
    Arm/Group Title Placebo Omalizumab MEDI4212 5 mg Subcutaneous MEDI4212 15 mg Subcutaneous MEDI4212 60 mg Subcutaneous MEDI4212 150 mg Subcutaneous MEDI4212 300 mg Subcutaneous MEDI4212 300 mg Intravenous
    Arm/Group Description A single dose of placebo matched to MEDI4212 subcutaneous injection or intravenous infusion on Day 1. 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. A single dose of MEDI4212 5 mg injection subcutaneously on Day 1. A single dose of MEDI4212 15 mg injection subcutaneously on Day 1. A single dose of MEDI4212 60 mg injection subcutaneously on Day 1. A single dose of MEDI4212 150 mg injection subcutaneously on Day 1. A single dose of MEDI4212 300 mg injection subcutaneously on Day 1. A single dose of MEDI4212 300 mg intravenous infusion over 120 minutes on Day 1.
    Period Title: Overall Study
    STARTED 17 6 3 3 16 19 14 8
    Treated 17 6 3 3 15 18 14 8
    COMPLETED 15 6 3 3 15 16 12 8
    NOT COMPLETED 2 0 0 0 1 3 2 0

    Baseline Characteristics

    Arm/Group Title Placebo Omalizumab MEDI4212 5 mg Subcutaneous MEDI4212 15 mg Subcutaneous MEDI4212 60 mg Subcutaneous MEDI4212 150 mg Subcutaneous MEDI4212 300 mg Subcutaneous MEDI4212 300 mg Intravenous Total
    Arm/Group Description A single dose of placebo matched to MEDI4212 subcutaneous injection or intravenous infusion on Day 1. 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. A single dose of MEDI4212 5 mg injection subcutaneously on Day 1. A single dose of MEDI4212 15 mg injection subcutaneously on Day 1. A single dose of MEDI4212 60 mg injection subcutaneously on Day 1. A single dose of MEDI4212 150 mg injection subcutaneously on Day 1. A single dose of MEDI4212 300 mg injection subcutaneously on Day 1. A single dose of MEDI4212 300 mg intravenous infusion over 120 minutes on Day 1. Total of all reporting groups
    Overall Participants 17 6 3 3 15 18 14 8 84
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    39.6
    (12.6)
    39.3
    (9.2)
    44.7
    (3.2)
    40.3
    (9.6)
    38.7
    (12.5)
    40.3
    (11.1)
    35.9
    (13.1)
    38.0
    (8.6)
    39.0
    (11.2)
    Sex: Female, Male (Count of Participants)
    Female
    7
    41.2%
    2
    33.3%
    1
    33.3%
    2
    66.7%
    4
    26.7%
    4
    22.2%
    2
    14.3%
    0
    0%
    22
    26.2%
    Male
    10
    58.8%
    4
    66.7%
    2
    66.7%
    1
    33.3%
    11
    73.3%
    14
    77.8%
    12
    85.7%
    8
    100%
    62
    73.8%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
    Description 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.
    Time Frame Day 1 to 85

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received any amount of investigational product and had safety data available.
    Arm/Group Title Placebo Omalizumab MEDI4212 5 mg Subcutaneous MEDI4212 15 mg Subcutaneous MEDI4212 60 mg Subcutaneous MEDI4212 150 mg Subcutaneous MEDI4212 300 mg Subcutaneous MEDI4212 300 mg Intravenous
    Arm/Group Description A single dose of placebo matched to MEDI4212 subcutaneous injection or intravenous infusion on Day 1. 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. A single dose of MEDI4212 5 mg injection subcutaneously on Day 1. A single dose of MEDI4212 15 mg injection subcutaneously on Day 1. A single dose of MEDI4212 60 mg injection subcutaneously on Day 1. A single dose of MEDI4212 150 mg injection subcutaneously on Day 1. A single dose of MEDI4212 300 mg injection subcutaneously on Day 1. A single dose of MEDI4212 300 mg intravenous infusion over 120 minutes on Day 1.
    Measure Participants 17 6 3 3 15 18 14 8
    TEAEs
    8
    47.1%
    2
    33.3%
    2
    66.7%
    1
    33.3%
    4
    26.7%
    9
    50%
    7
    50%
    6
    75%
    TESAEs
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2. Secondary Outcome
    Title Observed Serum Concentration
    Description Serum concentration of omalizumab and MEDI4212 were measured for participants who received omalizumab and MEDI4212, respectively.
    Time Frame Pre-dose and post-dose on Day 1; Day 2, 3, 5, 8, 15, 22, 29, 43, 57 and 85

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic (PK) population included all participants who received any investigational product and had a sufficient number of serum concentration measurements for computing PK parameters. Here 'n' signifies participants evaluable for this outcome measure at specified time point, for each group respectively
    Arm/Group Title Omalizumab MEDI4212 5 mg Subcutaneous MEDI4212 15 mg Subcutaneous MEDI4212 60 mg Subcutaneous MEDI4212 150 mg Subcutaneous MEDI4212 300 mg Subcutaneous MEDI4212 300 mg Intravenous
    Arm/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. A single dose of MEDI4212 5 mg injection subcutaneously on Day 1. A single dose of MEDI4212 15 mg injection subcutaneously on Day 1. A single dose of MEDI4212 60 mg injection subcutaneously on Day 1. A single dose of MEDI4212 150 mg injection subcutaneously on Day 1. A single dose of MEDI4212 300 mg injection subcutaneously on Day 1. A single dose of MEDI4212 300 mg intravenous infusion over 120 minutes on Day 1.
    Measure Participants 6 3 3 15 18 14 8
    Day 1 (predose) (n=0,1,0,0,2,1,1)
    NA
    (NA)
    96.76
    (NA)
    NA
    (NA)
    NA
    (NA)
    254.71
    (134.58)
    91.69
    (NA)
    158.32
    (NA)
    Day 1 (postdose) (n=0,0,0,0,0,0,8)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    110693
    (26060.2)
    Day 2 (n=5,1,1,12,17,13,8)
    8941.12
    (6361.95)
    100.36
    (NA)
    292.76
    (NA)
    3146.54
    (3820.61)
    6108.21
    (3401.45)
    14971.9
    (9608.63)
    88457.0
    (23398.4)
    Day 3 (n=5,1,1,12,17,14,8)
    13912.4
    (7546.50)
    110.12
    (NA)
    312.73
    (NA)
    3131.79
    (2513.43)
    7969.07
    (4004.75)
    14771
    (8692.16)
    69776.5
    (37738.7)
    Day 5 (n=5,1,1,11,16,14,8)
    17016.3
    (6806.15)
    116.44
    (NA)
    284.28
    (NA)
    3336.31
    (2759.69)
    7227.93
    (3210.9)
    15183.4
    (8522.98)
    34359.5
    (6817.40)
    Day 8 (n=5,0,1,9,16,14,8)
    16467.4
    (5374.97)
    NA
    (NA)
    190.38
    (NA)
    2368.21
    (1364.28)
    7144.03
    (5078.61)
    12611.1
    (8382.56)
    39290.2
    (32657.3)
    Day 15 (n=5,0,0,7,14,13,8)
    15099.6
    (5470.44)
    NA
    (NA)
    NA
    (NA)
    1134.39
    (259.41)
    4514.83
    (2864.46)
    8824.94
    (6744.55)
    11391.2
    (3673.21)
    Day 22 (n=5,0,0,6,12,10,8)
    12780.2
    (4657.23)
    NA
    (NA)
    NA
    (NA)
    521.3
    (96.73)
    3401
    (2140.78)
    7454.01
    (4682.86)
    4644.04
    (2571.96)
    Day 29 (n=5,0,0,4,11,8,7)
    9466.26
    (4040.07)
    NA
    (NA)
    NA
    (NA)
    212.22
    (82.96)
    2176.59
    (1390.94)
    2688.85
    (2191.8)
    2045.55
    (1814.12)
    Day 43 (n=5,2,0,0,5,5,3)
    5195.21
    (2263.08)
    121.39
    (8.11)
    NA
    (NA)
    NA
    (NA)
    1544.4
    (2068.43)
    1188.63
    (949.33)
    1669.74
    (739.22)
    Day 57 (n=5,2,0,0,4,4,3)
    2367.85
    (984.70)
    122.00
    (0.35)
    NA
    (NA)
    NA
    (NA)
    290.44
    (228.81)
    485.18
    (249.73)
    150.90
    (87.96)
    Day 85 (n=5,2,0,1, 3,1,1)
    829.55
    (434.33)
    104.07
    (2.48)
    NA
    (NA)
    98.62
    (NA)
    202.54
    (107.75)
    84.03
    (NA)
    176.87
    (NA)
    3. Secondary Outcome
    Title Number of Participants Exhibiting Anti-Drug Antibodies for MEDI4212 at Any Visit
    Description Anti-drug antibodies for MEDI4212 were analyzed for participants who received placebo or MEDI4212 as per planned analysis.
    Time Frame Days 1 (pre-dose), 15, 43, and 85

    Outcome Measure Data

    Analysis Population Description
    Immunogenicity population included all participants who received any investigational product and had at least one valid immunogenicity test result.
    Arm/Group Title Placebo MEDI4212 5 mg Subcutaneous MEDI4212 15 mg Subcutaneous MEDI4212 60 mg Subcutaneous MEDI4212 150 mg Subcutaneous MEDI4212 300 mg Subcutaneous MEDI4212 300 mg Intravenous
    Arm/Group Description A single dose of placebo matched to MEDI4212 subcutaneous injection or intravenous infusion on Day 1. A single dose of MEDI4212 5 mg injection subcutaneously on Day 1. A single dose of MEDI4212 15 mg injection subcutaneously on Day 1. A single dose of MEDI4212 60 mg injection subcutaneously on Day 1. A single dose of MEDI4212 150 mg injection subcutaneously on Day 1. A single dose of MEDI4212 300 mg injection subcutaneously on Day 1. A single dose of MEDI4212 300 mg intravenous infusion over 120 minutes on Day 1.
    Measure Participants 17 3 3 15 18 14 8
    Number [participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    6.7%
    0
    0%
    0
    0%
    4. Secondary Outcome
    Title Free Immunoglobulin E (IgE) Serum Concentration
    Description
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received any amount of investigational product and had safety data available. 'n' signifies those participants who evaluable for this outcome measure at specified time point for each group, respectively.
    Arm/Group Title Placebo Omalizumab MEDI4212 5 mg Subcutaneous MEDI4212 15 mg Subcutaneous MEDI4212 60 mg Subcutaneous MEDI4212 150 mg Subcutaneous MEDI4212 300 mg Subcutaneous MEDI4212 300 mg Intravenous
    Arm/Group Description A single dose of placebo matched to MEDI4212 subcutaneous injection or intravenous infusion on Day 1. 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. A single dose of MEDI4212 5 mg injection subcutaneously on Day 1. A single dose of MEDI4212 15 mg injection subcutaneously on Day 1. A single dose of MEDI4212 60 mg injection subcutaneously on Day 1. A single dose of MEDI4212 150 mg injection subcutaneously on Day 1. A single dose of MEDI4212 300 mg injection subcutaneously on Day 1. A single dose of MEDI4212 300 mg intravenous infusion over 120 minutes on Day 1.
    Measure Participants 17 6 3 3 15 18 14 8
    Day -28 (n=16,6,3,3,14,15,13,8)
    1160.79
    (1402.74)
    478.99
    (369.31)
    655.76
    (240.78)
    601.40
    (342.13)
    2170.63
    (3899.67)
    1976.98
    (3172.11)
    1775.68
    (2558.08)
    2641.68
    (2332.13)
    Day -1 (n=17,6,3,3,15,17,14,7)
    1025.19
    (1287.86)
    296.73
    (185.09)
    589.62
    (175.14)
    522.23
    (259.96)
    2453.85
    (3795.64)
    1655.06
    (2866.87)
    1681.82
    (2161.25)
    2772.55
    (2320.93)
    Day 1 (Predose) (n=17,6,3,3,15,17,14,8)
    1155.59
    (1447.09)
    410.78
    (289.39)
    552.30
    (168.96)
    558.69
    (305.68)
    2754.09
    (4468.96)
    1910.45
    (3268.58)
    1850.27
    (2435.13)
    2426.66
    (2460.85)
    Day 1:2 hours postdose (n=0,0,0,0,0,0,0,8)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    0.00
    (0.00)
    Day 2 (n=17,6,3,3,15,17,14,8)
    1183.10
    (1494.92)
    71.89
    (157.68)
    302.31
    (195.18)
    336.75
    (294.36)
    1584.76
    (3999.13)
    366.83
    (1499.49)
    94.19
    (351.27)
    0.00
    (0.00)
    Day 3 (n=17,6,3,3,15,17,14,8)
    1175.50
    (1550.93)
    74.29
    (168.46)
    282.12
    (179.53)
    293.78
    (259.88)
    1366.58
    (3496.19)
    248.20
    (1022.97)
    42.24
    (157.38)
    0.00
    (0.00)
    Day 5 (n=17,6,3,3,15,17,14,8)
    1131.87
    (1448.24)
    74.85
    (169.36)
    297.90
    (193.62)
    277.94
    (240.84)
    1401.33
    (3429.60)
    253.71
    (1045.75)
    0.53
    (1.43)
    0.00
    (0.00)
    Day 8 (n=17,6,3,3,15,17,14,8)
    1119.38
    (1417.95)
    85.00
    (192.16)
    366.17
    (239.65)
    288.20
    (250.03)
    1704.44
    (3822.59)
    362.27
    (1408.50)
    3.17
    (10.71)
    0.00
    (0.00)
    Day 15 (n=17,6,3,3,15,17,14,8)
    1081.11
    (1338.94)
    74.94
    (161.38)
    418.27
    (193.63)
    362.06
    (246.96)
    2102.53
    (4140.14)
    978.17
    (2490.21)
    209.71
    (539.11)
    0.00
    (0.00)
    Day 22 (n=17,6,3,3,15,17,14,8)
    1084.02
    (1294.17)
    70.95
    (145.36)
    453.89
    (191.07)
    406.12
    (264.19)
    2111.36
    (3730.60)
    1351.52
    (2803.98)
    788.30
    (1783.50)
    0.32
    (0.60)
    Day 29 (n=16,6,3,3,15,17,13,8)
    1185.82
    (1379.20)
    74.02
    (143.04)
    478.53
    (196.36)
    403.17
    (232.44)
    2153.91
    (3376.54)
    1676.12
    (3296.43)
    1468.72
    (3043.16)
    497.42
    (628.41)
    Day 43 (n=16,6,3,3,15,16,13,8)
    1089.90
    (1306.97)
    89.32
    (157.95)
    496.28
    (179.01)
    510.78
    (301.83)
    2712.59
    (4065.37)
    1928.37
    (3371.88)
    1912.71
    (2966.45)
    1674.54
    (1689.61)
    Day 57 (n=16,6,3,3,15,15,12,8)
    1055.20
    (1257.08)
    105.46
    (159.88)
    506.63
    (205.91)
    503.33
    (326.80)
    2201.38
    (3609.05)
    1394.92
    (2394.88)
    2306.44
    (3511.87)
    1978.31
    (1906.57)
    Day 85 (n=15,6,3,3,15,16,12,8)
    913.17
    (1142.25)
    294.89
    (377.39)
    526.93
    (227.80)
    530.49
    (292.24)
    2014.95
    (2952.69)
    1749.34
    (2799.68)
    2528.85
    (3967.57)
    2055.68
    (1822.85)

    Adverse Events

    Time Frame Day 1 to 85
    Adverse Event Reporting Description Safety population included all participants who received any amount of investigational product and had safety data available.
    Arm/Group Title Placebo Omalizumab MEDI4212 5 mg Subcutaneous MEDI4212 15 mg Subcutaneous MEDI4212 60 mg Subcutaneous MEDI4212 150 mg Subcutaneous MEDI4212 300 mg Subcutaneous MEDI4212 300 mg Intravenous
    Arm/Group Description A single dose of placebo matched to MEDI4212 subcutaneous injection or intravenous infusion on Day 1. 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. A single dose of MEDI4212 5 mg injection subcutaneously on Day 1. A single dose of MEDI4212 15 mg injection subcutaneously on Day 1. A single dose of MEDI4212 60 mg injection subcutaneously on Day 1. A single dose of MEDI4212 150 mg injection subcutaneously on Day 1. A single dose of MEDI4212 300 mg injection subcutaneously on Day 1. A single dose of MEDI4212 300 mg intravenous infusion over 120 minutes on Day 1.
    All Cause Mortality
    Placebo Omalizumab MEDI4212 5 mg Subcutaneous MEDI4212 15 mg Subcutaneous MEDI4212 60 mg Subcutaneous MEDI4212 150 mg Subcutaneous MEDI4212 300 mg Subcutaneous MEDI4212 300 mg Intravenous
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo Omalizumab MEDI4212 5 mg Subcutaneous MEDI4212 15 mg Subcutaneous MEDI4212 60 mg Subcutaneous MEDI4212 150 mg Subcutaneous MEDI4212 300 mg Subcutaneous MEDI4212 300 mg Intravenous
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/17 (0%) 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/15 (0%) 0/18 (0%) 0/14 (0%) 0/8 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo Omalizumab MEDI4212 5 mg Subcutaneous MEDI4212 15 mg Subcutaneous MEDI4212 60 mg Subcutaneous MEDI4212 150 mg Subcutaneous MEDI4212 300 mg Subcutaneous MEDI4212 300 mg Intravenous
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/17 (47.1%) 2/6 (33.3%) 2/3 (66.7%) 1/3 (33.3%) 4/15 (26.7%) 9/18 (50%) 7/14 (50%) 6/8 (75%)
    Cardiac disorders
    Palpitations 1/17 (5.9%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 0/8 (0%) 0
    Congenital, familial and genetic disorders
    Dermoid cyst 1/17 (5.9%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 0/8 (0%) 0
    Ear and labyrinth disorders
    Ear congestion 1/17 (5.9%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 0/8 (0%) 0
    Ear pain 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 1/8 (12.5%) 1
    Eye disorders
    Eye irritation 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/14 (0%) 0 0/8 (0%) 0
    Vision blurred 1/17 (5.9%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 0/8 (0%) 0
    Gastrointestinal disorders
    Diarrhoea 1/17 (5.9%) 1 0/6 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 0/8 (0%) 0
    Dry mouth 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 1/8 (12.5%) 1
    Dyspepsia 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 1/8 (12.5%) 1
    General disorders
    Fatigue 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/14 (0%) 0 0/8 (0%) 0
    Feeling hot 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 1/8 (12.5%) 1
    Injection site bruising 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/14 (0%) 0 0/8 (0%) 0
    Injection site pain 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/14 (7.1%) 1 0/8 (0%) 0
    Injection site paraesthesia 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/14 (7.1%) 1 0/8 (0%) 0
    Non-cardiac chest pain 1/17 (5.9%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 0/8 (0%) 0
    Infections and infestations
    Nasopharyngitis 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 2/8 (25%) 2
    Oral herpes 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/14 (0%) 0 0/8 (0%) 0
    Pharyngitis 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/14 (0%) 0 0/8 (0%) 0
    Upper respiratory tract infection 6/17 (35.3%) 6 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/15 (0%) 0 2/18 (11.1%) 2 2/14 (14.3%) 3 1/8 (12.5%) 1
    Urinary tract infection 1/17 (5.9%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 0/8 (0%) 0
    Injury, poisoning and procedural complications
    Muscle strain 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 1/8 (12.5%) 1
    Investigations
    Alanine aminotransferase increased 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 1/8 (12.5%) 1
    Aspartate aminotransferase increased 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 1/8 (12.5%) 1
    Blood creatine phosphokinase increased 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/14 (7.1%) 1 0/8 (0%) 0
    Gamma-glutamyltransferase increased 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 1/8 (12.5%) 1
    Metabolism and nutrition disorders
    Decreased appetite 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/14 (0%) 0 0/8 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 1/14 (7.1%) 1 0/8 (0%) 0
    Musculoskeletal chest pain 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/14 (0%) 0 0/8 (0%) 0
    Myalgia 0/17 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/14 (0%) 0 0/8 (0%) 0
    Nervous system disorders
    Dizziness 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/14 (0%) 0 2/8 (25%) 2
    Headache 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/14 (0%) 0 1/8 (12.5%) 1
    Nerve compression 0/17 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 0/8 (0%) 0
    Renal and urinary disorders
    Pollakiuria 0/17 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 0/8 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/14 (0%) 0 1/8 (12.5%) 1
    Bronchospasm 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 1/8 (12.5%) 1
    Dyspnoea 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 1/8 (12.5%) 1
    Nasal congestion 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 2/14 (14.3%) 2 0/8 (0%) 0
    Pulmonary congestion 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/14 (7.1%) 1 0/8 (0%) 0
    Rhinitis allergic 0/17 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 0/8 (0%) 0
    Skin and subcutaneous tissue disorders
    Dermatitis 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 1/14 (7.1%) 1 0/8 (0%) 0
    Dry skin 1/17 (5.9%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 0/8 (0%) 0
    Rash 0/17 (0%) 0 1/6 (16.7%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 0/8 (0%) 0
    Rash pruritic 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 1/8 (12.5%) 1
    Urticaria 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 3/18 (16.7%) 3 0/14 (0%) 0 2/8 (25%) 2
    Vascular disorders
    Flushing 0/17 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/14 (0%) 0 1/8 (12.5%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome. The PIs also agree for data to be presented first as a joint, multi-center publication.

    Results Point of Contact

    Name/Title Claire Birrell, Senior Clinical Scientist
    Organization MedImmune
    Phone 301-398-0000
    Email birrellc@medimmune.com
    Responsible Party:
    MedImmune LLC
    ClinicalTrials.gov Identifier:
    NCT01544348
    Other Study ID Numbers:
    • CD-RI-MEDI4212-1085
    First Posted:
    Mar 5, 2012
    Last Update Posted:
    Dec 30, 2014
    Last Verified:
    Dec 1, 2014