Clinical trial NCT01544348: A Phase 1, Randomized, Placebo-controlled, Dose-escalation Safety Study of MEDI4212 in Subjects With IgE >= 30 IU/mL
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Allergic Asthma
Atopic Dermatitis
Allergic Rhinitis
Healthy Volunteers
Keywords: Allergic
Atopic Dermatitis
MEDI4212
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2012-03-05
Enrollment: 295
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Phase 1 study to evaluate the safety of MEDI4212.

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).

Eligibility 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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 to 85
Secondary outcomes:
measure: Observed Serum Concentration
timeFrame: Pre-dose and post-dose on Day 1; Day 2, 3, 5, 8, 15, 22, 29, 43, 57 and 85
measure: Number of Participants Exhibiting Anti-Drug Antibodies for MEDI4212 at Any Visit
timeFrame: Days 1 (pre-dose), 15, 43, and 85
measure: Free Immunoglobulin E (IgE) Serum Concentration
timeFrame: 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
Other outcomes:
Locations:
city: Cypress
country: United States
facility: Research Site
state: California
city: Glendale
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Miami
country: United States
facility: Research Site
state: Florida
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Madison
country: United States
facility: Research Site
state: Wisconsin
Study officials:
References:
citation: 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.