Phase 1, Randomized, Placebo-controlled, Dose-escalation Safety Study of MEDI4212 in Allergic Subjects (MEDI42121085)

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 16, 2013
Last verified: December 2013
  Purpose

Phase 1 study to evaluate the safety of MEDI4212


Condition Intervention Phase
Allergic Asthma
Allergic Dermatitis
Allergic Rhinitis
Drug: Omalizumab
Drug: Placebo
Drug: MEDI4212
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: A Phase 1, Randomized, Placebo-controlled, Dose-escalation Study to Evaluate the Safety of MEDI4212 in Allergic Subjects

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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.


Enrollment: 86
Study Start Date: January 2012
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Omalizumab
Omalizumab will be used as a comparator to MEDI4212 in cohort 4a
Drug: Omalizumab
Xolair as active comparator
Other Name: Xolair
Placebo Comparator: Placebo
A placebo comparator will be used in a blinded fashion with active MEDI4212 in cohorts 1, 2, 3, 4b, 5, 6, 7, 8 and 9
Drug: Placebo
Placebo with all excipients and no active MEDI4212
Other Name: Placebo with all excipients and no active MEDI4212
Experimental: MED4212
Active
Drug: MEDI4212
Active
Other Name: Active MEDI4212

Detailed Description:

A Phase 1, Randomized, Placebo-controlled, Dose-escalation Study to Evaluate the Safety of MEDI4212 in Allergic Subjects

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age 18 through 60 years
  2. Written informed consent and any locally required authorization
  3. Body weight 45-150 kg for Cohorts 1-3, 4b, and 5-9. Body weight 45-90 kg for Cohort 4a
  4. Females must have been surgically sterilized or postmenopausal
  5. Nonsterilized 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
  6. Sterilized males must be at least 1-year post vasectomy or use a highly effective contraceptive method
  7. Healthy as determined by a responsible physician
  8. Current diagnosis of allergic rhinitis, allergic asthma, or atopic dermatitis (cohorts 1-6) with a diagnostic IgE of 30 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), > 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 IgE of ≥ 30 IU/mL
  9. Nonsmoker for ≥ 6 months
  10. Obsolete criteria as no longer require Positive in vitro IgE fluorescence enzyme immunoassay (FEIA) response
  11. A forced expiration volume in one second (FEV1) ≥ 80% predicted in subjects with asthma. Non-asthmatic subjects with FEV1 ≥ 80% predicted, or with FEV1 < 80% predicted but who, in the opinion of the investigator, do not have lung disease.
  12. Ability and willingness to complete the follow-up period through Day 85 as required by the protocol

Exclusion Criteria:

  1. 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
  2. Concurrent enrollment in another clinical study
  3. Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals
  4. Exposure to an anti-IgE MAb within 12 months prior to screening
  5. 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
  6. History of regular alcohol abuse within 12 months prior to screening
  7. 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
  8. 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 × upper limit of normal (ULN)

  9. Unwillingness or inability to follow the procedures outlined in the protocol
  10. Positive test or history of hepatitis B or positive hepatitis C
  11. Positive test or history of human immunodeficiency virus (HIV) or subject is known to be HIV seropositive
  12. History of cancer, with the exception of basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success
  13. Women who are pregnant, breastfeeding, or lactating
  14. Plans to donate blood during the study period
  15. Hyper-IgE syndrome or bronchopulmonary aspergillosis
  16. Prior history of Immune Complex Disease or type 3 hypersensitivity reactions to MAb administration
  17. Known history of prior infusion reaction to MAb administration
  18. History of untreated parasitic/helminthic infection within 6 months prior to screening
  19. Uses any of the following medications:

    1. Oral corticosteroids
    2. Medium to high dose ICS/LABA
    3. Immunosuppressives
    4. Beta blockers
  20. 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01544348

Locations
United States, California
Research Site
Cypress, California, United States
Research Site
Glendale, California, United States
United States, Colorado
Research Site
Denver, Colorado, United States
United States, Florida
Research Site
Miami, Florida, United States
United States, Maryland
Research Site
Baltimore, Maryland, United States
United States, Pennsylvania
Research Site
Pittsburgh, Pennsylvania, United States
United States, Wisconsin
Research Site
Madison, Wisconsin, United States
Sponsors and Collaborators
MedImmune LLC
  More Information

No publications provided

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01544348     History of Changes
Other Study ID Numbers: CD-RI-MEDI4212-1085
Study First Received: January 31, 2012
Last Updated: December 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by MedImmune LLC:
Allergic

Additional relevant MeSH terms:
Dermatitis
Dermatitis, Atopic
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Omalizumab
Anti-Allergic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on September 16, 2014