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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01544348
First received: January 31, 2012
Last updated: December 18, 2014
Last verified: December 2014

January 31, 2012
December 18, 2014
January 2012
June 2013   (final data collection date for primary outcome measure)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: Day 1 to 85 ] [ Designated as safety issue: Yes ]
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.
Safety [ Time Frame: 85 Days ] [ Designated as safety issue: Yes ]
The safety and tolerability of MEDI4212 will be assessed by summarizing adverse events (AEs) and serious adverse events (SAEs). The occurrence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) will be summarized immediately following the first administration of investigational product through the end of study (Day 85).
Complete list of historical versions of study NCT01544348 on ClinicalTrials.gov Archive Site
  • Observed Serum Concentration [ Time Frame: Pre-dose and post-dose on Day 1; Day 2, 3, 5, 8, 15, 22, 29, 43, 57 and 85 ] [ Designated as safety issue: No ]
    Serum concentration of omalizumab and MEDI4212 were measured for participants who received omalizumab and MEDI4212, respectively.
  • Number of Participants Exhibiting Anti-Drug Antibodies for MEDI4212 at Any Visit [ Time Frame: Days 1 (pre-dose), 15, 43, and 85 ] [ Designated as safety issue: Yes ]
    Anti-drug antibodies for MEDI4212 were analyzed for participants who received placebo or MEDI4212 as per planned analysis.
  • Free Immunoglobulin E (IgE) Serum Concentration [ 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 ] [ Designated as safety issue: Yes ]
  • Evaluation of the PK of MEDI4212 [ Time Frame: 85 Days ] [ Designated as safety issue: No ]
    The secondary endpoints of the study include PK and IM,and PD of MEDI4212 on free IgE levels following single SC or IV dosing. The PK parameters to be obtained and reported include: Cmax - the maximum observed serum concentration of MEDI4212 • Tmax - the time to maximum concentration ( or time of the observed Cmax) • AUC0-∞ - the area under the serum concentration-time curve from time zero to infinity • AUC0-t - the area under the serum concentration-time profile from time zero to the last measurable time point • t1/2 - the terminal elimination half-life • CL - systemic clearance
  • Evaluation of the IM of MEDI4212 [ Time Frame: 85 Days ] [ Designated as safety issue: No ]
    Immunogenicity The presence of ADA in serum will be assessed and results will be analyzed by summarizing the number and percentage of subjects who develop detectable ADA by treatment group. Anti-drug antibody titers will also be reported.
  • Effect of MEDI4212 on free IgE [ Time Frame: 85 Days ] [ Designated as safety issue: No ]
    Pharmacodynamics Serum free IgE will be assessed and the results are expected to be listed by treatment group and summarized for means at different time points. Changes from baseline will also be summarized.
Not Provided
Not Provided
 
A Phase 1, Randomized, Placebo-controlled, Dose-escalation Safety Study of MEDI4212 in Subjects With IgE >= 30 IU/mL
A Phase 1 Randomized, Placebo-controlled, Dose-escalation Study to Evaluate the Safety of MEDI4212 in Subjects With IgE >= 30 IU/mL

Phase 1 study to evaluate the safety of MEDI4212.

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).

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Allergic Asthma
  • Atopic Dermatitis
  • Allergic Rhinitis
  • Healthy Volunteers
  • Other: Placebo
    A single dose of placebo matched to MEDI4212 subcutaneous injection or intravenous infusion 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 Name: Xolair
  • Biological: MEDI4212 5 mg Subcutaneous
    A single dose of MEDI4212 5 mg injection subcutaneously on Day 1.
  • Biological: MEDI4212 15 mg Subcutaneous
    A single dose of MEDI4212 15 mg injection subcutaneously on Day 1.
  • Biological: MEDI4212 60 mg Subcutaneous
    A single dose of MEDI4212 60 mg injection subcutaneously on Day 1.
  • Biological: MEDI4212 150 mg Subcutaneous
    A single dose of MEDI4212 150 mg injection subcutaneously on Day 1.
  • Biological: MEDI4212 300 mg Subcutaneous
    A single dose of MEDI4212 300 mg injection subcutaneously on Day 1.
  • Biological: MEDI4212 300 mg Intravenous
    A single dose of MEDI4212 300 mg intravenous infusion over 120 minutes on Day 1.
  • Placebo Comparator: Placebo
    A single dose of placebo matched to MEDI4212 subcutaneous injection or intravenous infusion on Day 1.
    Intervention: Other: Placebo
  • 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.
    Intervention: Biological: Omalizumab
  • Experimental: MEDI4212 5 mg Subcutaneous
    A single dose of MEDI4212 5 mg injection subcutaneously on Day 1.
    Intervention: Biological: MEDI4212 5 mg Subcutaneous
  • Experimental: MEDI4212 15 mg Subcutaneous
    A single dose of MEDI4212 15 mg injection subcutaneously on Day 1.
    Intervention: Biological: MEDI4212 15 mg Subcutaneous
  • Experimental: MEDI4212 60 mg Subcutaneous
    A single dose of MEDI4212 60 mg injection subcutaneously on Day 1.
    Intervention: Biological: MEDI4212 60 mg Subcutaneous
  • Experimental: MEDI4212 150 mg Subcutaneous
    A single dose of MEDI4212 150 mg injection subcutaneously on Day 1.
    Intervention: Biological: MEDI4212 150 mg Subcutaneous
  • Experimental: MEDI4212 300 mg Subcutaneous
    A single dose of MEDI4212 300 mg injection subcutaneously on Day 1.
    Intervention: Biological: MEDI4212 300 mg Subcutaneous
  • Experimental: MEDI4212 300 mg Intravenous
    A single dose of MEDI4212 300 mg intravenous infusion over 120 minutes on Day 1.
    Intervention: Biological: MEDI4212 300 mg Intravenous
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
295
June 2013
June 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years to 60 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01544348
CD-RI-MEDI4212-1085
Yes
MedImmune LLC
MedImmune LLC
Not Provided
Not Provided
MedImmune LLC
December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP