Resumen

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.

Descripción detallada

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.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 65 YearsSexo: ALL

Criterios de inclusión

Subjects must meet all of the following criteria:
Male or female
Age 18 through 65 years at the time of screening
Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
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
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
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)
Sterilized males must be at least 1-year post vasectomy and have obtained documentation of the absence of sperm in the ejaculate
Weight ≥ 45 kg but ≤ 120 kg and body mass index (BMI) between 18 and 35 kg/m2
Physician-diagnosed asthma by medical chart
Currently taking inhaled corticosteroids (ICS) or is a candidate to receive ICS per Expert Panel Report (EPR)-3
Pre-bronchodilator forced expiratory volume in 1 second (FEV1) value ≥ 40% at Day -28 and Day 1
A post-bronchodilator increase in FEV1 and/or FVC ≥ 12% and ≥ 200 mL at Day -28 OR meeting any one of the following criteria:
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
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

Criterios de exclusión

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
An Asthma Control Questionnaire (ACQ) score ≥ 1.5 at Day -28 and at Day 1.
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
Ability and willingness to complete the follow-up period through Day 323 as required by the protocol.
Any of the following would exclude the subject from participation in the study:
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
Known history of allergy or reaction to any component of the investigational product formulation
History of anaphylaxis to other biologic therapy
Lung disease other than asthma (eg, chronic obstructive pulmonary disease \[COPD\], cystic fibrosis)
Severe depression as measured by a depression score \> 15 on the Hospital Anxiety and Depression Scale (HADS) at either Day-28 or Day 1.
History of suicidal behavior in the previous 3 years as measured by the Columbia Suicide Severity Rating Scale (C-SSRS) at Day -28.
Acute illness other than asthma at the screening and randomization visits
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
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
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
Receipt of immunoglobulin or blood products within 28 days before randomization
Plans to donate blood during the entire study period
Donated blood or has had a blood transfusion within 28 days before screening
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
Receipt of any biologicals including MEDI-528 within 5 half-lives before the first dose of investigational product in this study
History of any known immunodeficiency disorder
A positive hepatitis B surface antigen, or hepatitis C virus antibody, as determined by medical history and/or subject's verbal report
A positive human immunodeficiency virus test or is taking antiretroviral medications, as determined by medical history and/or subject's verbal report
A live attenuated vaccination received within 28 days before screening
History of clinically significant abnormality on electrocardiogram (ECG) in the opinion of the investigator
Breastfeeding or lactating
History of treatment for alcohol or drug abuse within the past year
History suggestive of COPD or of tobacco smoking ≥ 10 pack-years
Evidence of any uncontrolled systemic disease upon physical examination
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
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
Individuals who are legally institutionalized

Intervenciones

biological

MEDI528 30 mg

MEDI-528 at a dose of 30 mg administered as a subcutaneous injection every 2 weeks for 24 weeks

biological

MEDI528 100 mg

MEDI-528 at a dose of 100 mg administered as a subcutaneous injection every 2 weeks for 24 weeks

biological

MEDI528 300 mg

MEDI-528 at a dose of 300 mg administered as a subcutaneous injection every 2 weeks for 24 weeks

other

Placebo

Placebo administered as a subcutaneous injection every 2 weeks for 24 weeks

Ubicaciones

Research Site

Buenos Aire, Buenos Aires F.D., Argentina

Research Site

Ciudad Autonoma Bs As, Buenos Aires F.D., Argentina

Research Site

Rosario, Santa Fe Province, Argentina

Research Site

San Miguel de Tucumán, Tucumán Province, Argentina

Research Site

Buenos Aires, Argentina

Research Site

Ciudad de Buenos Aire, Argentina

A Phase 2b, Randomized Study to Evaluate the Efficacy and Safety of Subcutaneous MEDI-528 in Adults With Uncontrolled Asthma

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

MEDI528 30 mg

MEDI528 100 mg

MEDI528 300 mg

Placebo

Ubicaciones

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Patrocinadores