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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01544348
• Other study ID #: CD-RI-MEDI4212-1085
• Status: Completed
• Phase: Phase 1
• First received: January 31, 2012
• Last updated: December 18, 2014
• Start date: January 2012
• Est. completion date: June 2013

Study information

• Verified date: December 2014
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Phase 1 study to evaluate the safety of MEDI4212.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 295
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Allergic Asthma
• Allergic Rhinitis
• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema
• Healthy Volunteers

Intervention

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.
• MEDI4212 5 mg Subcutaneous
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.
• MEDI4212 60 mg Subcutaneous
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.
• MEDI4212 300 mg Subcutaneous
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.

Locations

Country	Name	City	State
United States	Research Site	Baltimore	Maryland
United States	Research Site	Cypress	California
United States	Research Site	Denver	Colorado
United States	Research Site	Glendale	California
United States	Research Site	Madison	Wisconsin
United States	Research Site	Miami	Florida
United States	Research Site	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	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.	Day 1 to 85	Yes
Secondary	Observed Serum Concentration	Serum concentration of omalizumab and MEDI4212 were measured for participants who received omalizumab and MEDI4212, respectively.	Pre-dose and post-dose on Day 1; Day 2, 3, 5, 8, 15, 22, 29, 43, 57 and 85	No
Secondary	Number of Participants Exhibiting Anti-Drug Antibodies for MEDI4212 at Any Visit	Anti-drug antibodies for MEDI4212 were analyzed for participants who received placebo or MEDI4212 as per planned analysis.	Days 1 (pre-dose), 15, 43, and 85	Yes
Secondary	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	Yes