A Study to Evaluate the Effectiveness and Safety of MEDI-528 in Adults

This study has been completed.
Sponsor:
Information provided by:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00968669
First received: August 28, 2009
Last updated: August 5, 2013
Last verified: August 2013

August 28, 2009
August 5, 2013
December 2009
November 2011   (final data collection date for primary outcome measure)
Asthma Control Questionnaire (ACQ) score [ Time Frame: Day 92 ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00968669 on ClinicalTrials.gov Archive Site
To evaluate safety and tolerability of MEDI-528 on asthma exacerbations, asthma control, pulmonary function, and health-related quality of life; and PK and IM of MEDI-528. [ Time Frame: Day 323 ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
A Study to Evaluate the Effectiveness and Safety of MEDI-528 in Adults
A Phase 2b, Randomized Study to Evaluate the Efficacy and Safety of Subcutaneous MEDI-528 in Adults With Uncontrolled Asthma

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

The primary objective of this study is to evaluate the effect of multiple-dose subcutaneous (SC) administration of MEDI-528 on asthma control in adults with uncontrolled, moderate-to-severe, persistent asthma.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Asthma
  • Biological: MEDI-528
    30 mg; Study Days 1, 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155, and 169.
  • Biological: MEDI-528
    100 mg; Study Days 1, 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155, and 169.
  • Biological: MEDI-528
    300 mg; Study Days 1, 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155, and 169.
  • Other: Placebo
    0 mg; Study Days 1, 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155, and 169.
  • Experimental: 1
    Investigational product-MEDI-528
    Intervention: Biological: MEDI-528
  • Experimental: 2
    Investigational Product MEDI-528
    Intervention: Biological: MEDI-528
  • Experimental: 3
    Investigational product-MEDI-528
    Intervention: Biological: MEDI-528
  • Experimental: 4
    Placebo
    Intervention: Other: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
329
January 2012
November 2011   (final data collection date for primary outcome measure)

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 (eg, HIPAA in the USA, EU Data Privacy Directive in the EU, 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. In this study, where medications and devices containing hormones are included, the recommended methods of contraception are described in Table 4.2.1-1. 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 (ie, ≥ 100 lb but ≤ 265 lb) and body mass index (BMI) between 18 and 35 kg/m2
  6. Physician-diagnosed asthma by medical chart
  7. Currently taking ICS or is a candidate to receive ICS per Expert Panel Report (EPR)-3 (National Heart, Lung, and Blood Institute, 2007)
  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 [PC20 ≤ 8 mg/mL (ATS, 2000)] 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 (PC20 ≤ 8 mg/mL), 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 ACQ score ≥ 1.5 at Day -28 and at Day 1 (ACQ is described in Section 5.3.11.1). Subject may be re-screened one additional time if they met this criterion at Day -28 but failed to meet it at Day 1 (procedure described in Section 4.6.1)
  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; see Appendix 7) 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; see Appendix 8 [Baseline 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 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
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Brazil,   Canada,   Colombia,   Costa Rica,   Panama,   Peru,   Philippines,   Taiwan
 
NCT00968669
MI-CP198
Yes
Medical Monitor, MedImmune, LLC
MedImmune LLC
Not Provided
Study Director: David Gossage, M.D., MBA MedImmune LLC
MedImmune LLC
August 2013

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