A Study to Evaluate the Effectiveness and Safety of MEDI-528 in Adults
Condition: Asthma
MeSH terms: Asthma
Intervention: MEDI528 30 mg; MEDI528 100 mg; MEDI528 300 mg; Placebo
Intervention description: MEDI-528 at a dose of 30 mg administered as a subcutaneous injection every 2 weeks for 24 weeks; MEDI-528 at a dose of 100 mg administered as a subcutaneous injection every 2 weeks for 24 weeks; MEDI-528 at a dose of 300 mg administered as a subcutaneous injection every 2 weeks for 24 weeks; Placebo administered as a subcutaneous injection every 2 weeks for 24 weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 329.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      To study the effectiveness and safety of multiple-doses of MEDI-528 on asthma control in
      adult participants with uncontrolled, moderate-to-severe, persistent asthma.
    

Eligibility criteria:

        Inclusion Criteria

        Subjects must meet all of the following criteria:

          1. Male or female

          2. Age 18 through 65 years at the time of screening

          3. Written informed consent and any locally required authorization obtained from the
             subject prior to performing any protocol-related procedures, including screening
             evaluations

          4. Female subjects of childbearing potential who are sexually active with non-sterilized
             male partner must use adequate contraception from screening through the end of the
             study. An acceptable method of contraception is defined as one that has no higher than
             a 1% failure rate. Sustained abstinence is an acceptable practice; however, periodic
             abstinence, the rhythm method, and the withdrawal method are not acceptable methods of
             contraception

               1. Non-sterilized males who are sexually active with a female of child-bearing
                  potential must use adequate contraception from screening through the end of the
                  study

               2. Females or female partners not of childbearing potential must have been
                  surgically sterilized (eg, hysterectomy, bilateral tubal ligation, or bilateral
                  oophorectomy) or postmenopausal (defined as at least 1 year since last regular
                  menses)

               3. Sterilized males must be at least 1-year post vasectomy and have obtained
                  documentation of the absence of sperm in the ejaculate

          5. Weight ≥ 45 kg but ≤ 120 kg and body mass index (BMI) between 18 and 35 kg/m2

          6. Physician-diagnosed asthma by medical chart

          7. Currently taking inhaled corticosteroids (ICS) or is a candidate to receive ICS per
             Expert Panel Report (EPR)-3

          8. Pre-bronchodilator forced expiratory volume in 1 second (FEV1) value ≥ 40% at Day -28
             and Day 1

          9. A post-bronchodilator increase in FEV1 and/or FVC ≥ 12% and ≥ 200 mL at Day -28 OR
             meeting any one of the following criteria:

               1. Proof of post-bronchodilator reversibility of airflow obstruction ≥ 12%
                  documented within 36 months prior to randomization or proof of a positive
                  response to a methacholine challenge documented within 36 months prior to
                  randomization; OR

               2. Proof of partial reversibility of ≥ 8% to < 12% improvement in
                  post-bronchodilator FEV1 on Day -28 and achievement of ≥ 12% reversibility at a
                  second time between Day -27 and Day -15; OR

               3. If a) and b) are not met and all other inclusion/exclusion criteria are met,
                  subjects with a FEV1 of ≥ 1.5 L and ≥ 60% on Day -14 will be eligible to undergo
                  a methacholine challenge. If the subject achieves a positive response to this
                  methacholine challenge, then this criterion is met

         10. Uncontrolled asthma consistent with EPR-3. In the 28 days before screening, subjects
             should have a history of one or more of the following:

               -  Daytime asthma symptoms ≥ 2 days/week

               -  Nighttime awakening ≥ 1 night/week

               -  Albuterol/salbutamol use ≥ 2 days/week

         11. An Asthma Control Questionnaire (ACQ) score ≥ 1.5 at Day -28 and at Day 1.

         12. At least one asthma exacerbation in the 12 months before screening that required
             intake of systemic corticosteroids after an unscheduled medical encounter or as agreed
             with a physician based on an asthma action plan that defines when oral steroids can be
             taken by the subject

         13. Ability and willingness to complete the follow-up period through Day 323 as required
             by the protocol.

        Exclusion Criteria

        Any of the following would exclude the subject from participation in the study:

          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. Known history of allergy or reaction to any component of the investigational product
             formulation

          5. History of anaphylaxis to other biologic therapy

          6. Lung disease other than asthma (eg, chronic obstructive pulmonary disease [COPD],
             cystic fibrosis)

          7. Severe depression as measured by a depression score > 15 on the Hospital Anxiety and
             Depression Scale (HADS) at either Day-28 or Day 1.

          8. History of suicidal behavior in the previous 3 years as measured by the Columbia
             Suicide Severity Rating Scale (C-SSRS) at Day -28.

          9. Acute illness other than asthma at the screening and randomization visits

         10. History of an active infection within 28 days before and during the screening period,
             or evidence of clinically significant active infection, including ongoing chronic
             infection

         11. History of ingestion of untreated water in a location known to be infected with
             parasites, resulting in acute or chronic diarrhea; history of recent travel to areas
             where parasite infestations are endemic within 6 months before screening; or a
             diagnosis of parasitic infection within 6 months before screening

         12. Use of immunosuppressive medication (except oral prednisone up to a dose of 20 mg
             every other day or equivalent [eg, 10 mg a day or 5 mg twice a day] and inhaled and
             topical corticosteroids) within 28 days before randomization

         13. Receipt of immunoglobulin or blood products within 28 days before randomization

         14. Plans to donate blood during the entire study period

         15. Donated blood or has had a blood transfusion within 28 days before screening

         16. Receipt of any non-biological study drugs or interventional therapy (including
             surgical procedures) within 28 days of the first dose of investigational product in
             this study

         17. Receipt of any biologicals including MEDI-528 within 5 half-lives before the first
             dose of investigational product in this study

         18. History of any known immunodeficiency disorder

         19. A positive hepatitis B surface antigen, or hepatitis C virus antibody, as determined
             by medical history and/or subject's verbal report

         20. A positive human immunodeficiency virus test or is taking antiretroviral medications,
             as determined by medical history and/or subject's verbal report

         21. A live attenuated vaccination received within 28 days before screening

         22. History of clinically significant abnormality on electrocardiogram (ECG) in the
             opinion of the investigator

         23. Breastfeeding or lactating

         24. History of treatment for alcohol or drug abuse within the past year

         25. History suggestive of COPD or of tobacco smoking ≥ 10 pack-years

         26. Evidence of any uncontrolled systemic disease upon physical examination

         27. History of cancer, apart from basal cell carcinoma or in situ carcinoma of the cervix
             treated with apparent success with curative therapy ≥ 1 year before Day 1 or other
             malignancies treated with apparent success with curative therapy ≥ 5 years before
             screening

         28. Any noninfectious disease involving multiple organs (eg, cystic fibrosis, systemic
             lupus erythematosus, hemophilia, multiple sclerosis, etc.) that, in the opinion of the
             investigator, would interfere with evaluation of the investigational product or
             interpretation of subject safety or study results

         29. Individuals who are legally institutionalized