Clinical trial NCT00968669: A Study to Evaluate the Effectiveness and Safety of MEDI-528 in Adults
Official title: A Phase 2b, Randomized Study to Evaluate the Efficacy and Safety of Subcutaneous MEDI-528 in Adults With Uncontrolled Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2009-08-31
Enrollment: 329
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

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

Primary outcomes:
measure: Change at Day 92 From Baseline in Mean Asthma Control Questionnaire (ACQ) Scores (Intent-toTreat Analysis)
timeFrame: Day 92
Secondary outcomes:
measure: Weighted Asthma Exacerbation Rate Through Day 92 (Intent-to-Treat Analysis)
timeFrame: Days 1 - 92
measure: Weighted Asthma Exacerbation Rate Through Day 176 (Intent-to-Treat Analysis)
timeFrame: Days 1 - 176
measure: Proportion of Participants Experiencing at Least One Asthma Exacerbation Through Day 92 (Intent-to-Treat Analysis)
timeFrame: Days 1 - 92
measure: Proportion of Participants Experiencing at Least One Asthma Exacerbation Through Day 176 (Intent-to-Treat Analysis)
timeFrame: Days 1 - 176
measure: Time to First Asthma Exacerbation Through Day 92 (Intent-to-Treat Analysis)
timeFrame: Days 1 - 92
measure: Time to First Asthma Exacerbation Through Day 176 (Intent-to-Treat Analysis)
timeFrame: Days 1 - 176
measure: Change at Day 176 From Baseline in Mean Asthma Control Questionnaire Scores (Intent-to-Treat Analysis)
timeFrame: Day 176
measure: Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 92 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis)
timeFrame: Day 92
measure: Proportion of Participants Achieving Mean Asthma Control Questionnaire (ACQ) Scores at Day 176 of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 (Intent-to-Treat Analysis)
timeFrame: Day 176
measure: Time to First Observed Mean Asthma Control Questionnaire (ACQ) Change From Baseline > or = 0.5 Through Day 92 (Intent-to-Treat Analysis)
timeFrame: Days 1 - 92
measure: Time to First Observed Mean Asthma Control Questionnaire (ACQ) Change From Baseline > or = 0.5 Through Day 176 (Intent-to-Treat Analysis)
timeFrame: Days 1 - 176
measure: Change at Day 92 From Baseline in Forced Expiratory Volume in One Second (FEV1) (Intent-to-Treat Analysis)
timeFrame: Day 92
measure: Change at Day 176 From Baseline in Forced Expiratory Volume in One Second (FEV1) (Intent-to-Treat Analysis)
timeFrame: Day 176
measure: Proportion of Participants Who Had a Asthma Quality of Life Questionnaire - Standard (AQLQ[S]) Assessment Response at Day 85 (Intent-to-Treat Analysis)
timeFrame: Day 85
measure: Proportion of Participants Who Had a Asthma Quality of Life Questionnaire - Standard (AQLQ[S]) Assessment Response at Day 176 (Intent-to-Treat Analysis)
timeFrame: Day 176
measure: Proportion of Participants With Detectable Anti-drug Antibodies to MEDI-528
timeFrame: Days 1, 29, 57, 85, 127, 169, 176, 204,260, and 323
measure: First Dose Trough Concentration of MEDI-528
timeFrame: Day 15
measure: Day 169 Steady State Trough Concentration of MEDI-528
timeFrame: Day 169
measure: Half Life of MEDI-528
timeFrame: Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323
measure: Accumulation Ratio of Trough Concentrations of MEDI-528
timeFrame: Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323
Other outcomes:
Locations:
city: Pell City
country: United States
facility: Research Site
state: Alabama
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Sacramento
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Centennial
country: United States
facility: Research Site
state: Colorado
city: Colarado Springs
country: United States
facility: Research Site
state: Colorado
city: Thornton
country: United States
facility: Research Site
state: Colorado
city: Waterbury
country: United States
facility: Research Site
state: Connecticut
city: Kissimmee
country: United States
facility: Research Site
state: Florida
city: Normal
country: United States
facility: Research Site
state: Illinois
city: Overland Park
country: United States
facility: Research Site
state: Kansas
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Silver Spring
country: United States
facility: Research Site
state: Maryland
city: N. Dartmouth
country: United States
facility: Research Site
state: Massachusetts
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Mt. Laurel
country: United States
facility: Research Site
state: New Jersey
city: Sylvania
country: United States
facility: Research Site
state: Ohio
city: Medford
country: United States
facility: Research Site
state: Oregon
city: Lincoln
country: United States
facility: Research Site
state: Rhode Island
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: El Paso
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Buenos Aire
country: Argentina
facility: Research Site
state: Caba
city: Ciudad Autonoma Bs As
country: Argentina
facility: Research Site
state: Ciudad de Buenos Aires
city: Rosario
country: Argentina
facility: Research Site
state: Santa Fe
city: San Miguel de Tucuman
country: Argentina
facility: Research Site
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Research Site
city: Ciudad de Buenos Aire
country: Argentina
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
state: RS
city: Porto Alegre
country: Brazil
facility: Research Site
state: RS
city: Florianopolis
country: Brazil
facility: Research Site
state: Santa Catarina
city: Santo André
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Mississauga
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Quebec City
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Bogota DC
country: Colombia
facility: Research Site
state: Cundinamarca
city: Bogota
country: Colombia
facility: Research Site
state: Cundinamarca
city: Bogotá D.C.
country: Colombia
facility: Research Site
state: Cundinamarca
city: San Francisco de Dos Rios
country: Costa Rica
facility: Research Site
state: San José
city: Ciudad de Panama
country: Panama
facility: Research Site
city: Jesus Maria
country: Peru
facility: Research Site
state: Lima
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lipa City
country: Philippines
facility: Research Site
state: Batangas
city: Iloilo City
country: Philippines
facility: Research Site
state: Iloilo
city: Quezon City
country: Philippines
facility: Research Site
state: Metro Manila
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: Chad Oh, M.D.
role: STUDY_DIRECTOR
References:
citation: Oh CK, Leigh R, McLaurin KK, Kim K, Hultquist M, Molfino NA. A randomized, controlled trial to evaluate the effect of an anti-interleukin-9 monoclonal antibody in adults with uncontrolled asthma. Respir Res. 2013 Sep 19;14(1):93. doi: 10.1186/1465-9921-14-93.
citation: Lloyd CM, Hessel EM. Functions of T cells in asthma: more than just T(H)2 cells. Nat Rev Immunol. 2010 Dec;10(12):838-48. doi: 10.1038/nri2870. Epub 2010 Nov 9.