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

Asthma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00968669
• Other study ID #: MI-CP198
• Status: Completed
• Phase: Phase 2
• First received: August 28, 2009
• Last updated: May 6, 2014
• Start date: December 2009
• Est. completion date: January 2012

Study information

• Verified date: May 2014
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 329
• Est. completion date: January 2012
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Biological:
• MEDI528 30 mg
MEDI-528 at a dose of 30 mg administered as a subcutaneous injection every 2 weeks for 24 weeks
• MEDI528 100 mg
MEDI-528 at a dose of 100 mg administered as a subcutaneous injection every 2 weeks for 24 weeks
• 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

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aire	Caba
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Ciudad Autonoma Bs As	Ciudad de Buenos Aires
Argentina	Research Site	Ciudad de Buenos Aire
Argentina	Research Site	Rosario	Santa Fe
Argentina	Research Site	San Miguel de Tucuman	Tucuman
Brazil	Research Site	Florianopolis	Santa Catarina
Brazil	Research Site	Porto Alegre	RS
Brazil	Research Site	Porto Alegre	RS
Brazil	Research Site	Santo André
Brazil	Research Site	Sao Paulo
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Mississauga	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Quebec City	Quebec
Canada	Research Site	Vancouver	British Columbia
Colombia	Research Site	Bogota	Cundinamarca
Colombia	Research Site	Bogotá D.C.	Cundinamarca
Colombia	Research Site	Bogota DC	Cundinamarca
Costa Rica	Research Site	San Francisco de Dos Rios	San José
Panama	Research Site	Ciudad de Panama
Peru	Research Site	Jesus Maria	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Philippines	Research Site	Iloilo City	Iloilo
Philippines	Research Site	Lipa City	Batangas
Philippines	Research Site	Quezon City	Metro Manila
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taoyuan
United States	Research Site	Baltimore	Maryland
United States	Research Site	Centennial	Colorado
United States	Research Site	Colarado Springs	Colorado
United States	Research Site	El Paso	Texas
United States	Research Site	Greenville	South Carolina
United States	Research Site	Kissimmee	Florida
United States	Research Site	Lincoln	Rhode Island
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Medford	Oregon
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Mt. Laurel	New Jersey
United States	Research Site	N. Dartmouth	Massachusetts
United States	Research Site	Normal	Illinois
United States	Research Site	Omaha	Nebraska
United States	Research Site	Overland Park	Kansas
United States	Research Site	Pell City	Alabama
United States	Research Site	Sacramento	California
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	Silver Spring	Maryland
United States	Research Site	Sylvania	Ohio
United States	Research Site	Thornton	Colorado
United States	Research Site	Waterbury	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Colombia,  Costa Rica,  Panama,  Peru,  Philippines,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change at Day 92 From Baseline in Mean Asthma Control Questionnaire (ACQ) Scores (Intent-toTreat Analysis)	Change at Day 92 from baseline (Day 1, prior to dosing) in mean ACQ scores in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of = 0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score = 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful.	Day 92	No
Secondary	Weighted Asthma Exacerbation Rate Through Day 92 (Intent-to-Treat Analysis)	Weighted asthma exacerbation rate (total number of exacerbation rate in each group per total duration of participant-year follow-up in each group) between Day 1 and Day 92 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy.	Days 1 - 92	No
Secondary	Weighted Asthma Exacerbation Rate Through Day 176 (Intent-to-Treat Analysis)	Weighted asthma exacerbation rate (total number of exacerbation rate in each group per total duration of participant-year follow-up in each group) between Day 1 and Day 176 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy.	Days 1 - 176	No
Secondary	Proportion of Participants Experiencing at Least One Asthma Exacerbation Through Day 92 (Intent-to-Treat Analysis)	The proportion of participants that experienced at least one asthma exacerbation between Day 1 and Day 92 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy.	Days 1 - 92	No
Secondary	Proportion of Participants Experiencing at Least One Asthma Exacerbation Through Day 176 (Intent-to-Treat Analysis)	The proportion of participants that experienced at least one asthma exacerbation between Day 1 and Day 176 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy.	Days 1 - 176	No
Secondary	Time to First Asthma Exacerbation Through Day 92 (Intent-to-Treat Analysis)	Time to first asthma exacerbation between Day 1 and Day 92 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy.	Days 1 - 92	No
Secondary	Time to First Asthma Exacerbation Through Day 176 (Intent-to-Treat Analysis)	Time to first asthma exacerbation between Day 1 and Day 176 in pariticpants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). An exacerbation was defined as a progressive increase of asthma symptoms AND a reduction of 20% or more in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) from baseline (Day 1, prior to dosing) or best previously measured value prior to the current event that did not resolve after the initiation of rescue medications; and results in a prescription for/or administration of systemic corticosteroid burst therapy by the investigator or health care provider. An exacerbation event was considered resolved when the subject's asthma symptoms diminished and PEF or FEV1 return to greater than 80% of baseline for 7 or more days after completion of systemic corticosteroid burst therapy.	Days 1 - 176	No
Secondary	Change at Day 176 From Baseline in Mean Asthma Control Questionnaire Scores (Intent-to-Treat Analysis)	Change at Day 176 from baseline (Day 1, prior to dosing) in mean ACQ scores in participants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of = 0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score = 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful.	Day 176	No
Secondary	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)	Proportion of participants achieving mean ACQ scores of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 at Day 92 in participants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of = 0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score = 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful.	Day 92	No
Secondary	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)	Proportion of participants achieving mean ACQ scores of < or = 0.75, > 0.75 to < 1.5, and > or = 1.5 at Day 176 in participants receiving 30, 100, or 300 mg MEDI-528 versus placebo (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of = 0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score = 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful.	Day 176	No
Secondary	Time to First Observed Mean Asthma Control Questionnaire (ACQ) Change From Baseline > or = 0.5 Through Day 92 (Intent-to-Treat Analysis)	Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the time to first observed mean ACQ change from baseline (Day 1, prior to dosing) > or = 0.5 through Day 92 (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of = 0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score = 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful.	Days 1 - 92	No
Secondary	Time to First Observed Mean Asthma Control Questionnaire (ACQ) Change From Baseline > or = 0.5 Through Day 176 (Intent-to-Treat Analysis)	Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the time to first observed mean ACQ change from baseline (Day 1, prior to dosing) > or = 1.5 Through Day 176 (Intent-to-Treat Analysis). The 6-item ACQ is a participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and daily rescue bronchodilator use. Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score is the mean of the responses. Mean scores of = 0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score = 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful.	Days 1 - 176	No
Secondary	Change at Day 92 From Baseline in Forced Expiratory Volume in One Second (FEV1) (Intent-to-Treat Analysis)	Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the mean change at Day 92 from baseline (Day 1, prior to dosing) in FEV1.	Day 92	No
Secondary	Change at Day 176 From Baseline in Forced Expiratory Volume in One Second (FEV1) (Intent-to-Treat Analysis)	Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the mean change from baseline (Day 1, prior to dosing) in FEV1 at Day 176	Day 176	No
Secondary	Proportion of Participants Who Had a Asthma Quality of Life Questionnaire - Standard (AQLQ[S]) Assessment Response at Day 85 (Intent-to-Treat Analysis)	Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the proportion of participants who had an AQLQ(S) assessment response (defined as an improvement of at least 0.5 score in AQLQ[S]) at Day 85 (Intent-to-Treat Analysis). The AQLQ(S) is a 32-item questionnaire that measures the health related quality of life experienced by asthma patients. In the study, participants were asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score is calculated as the mean response to all questions. Individual improvement in the overall score of 0.5 has been identified as the minimally important difference, with score changes > 1.5 identified to be large meaningful differences.	Day 85	No
Secondary	Proportion of Participants Who Had a Asthma Quality of Life Questionnaire - Standard (AQLQ[S]) Assessment Response at Day 176 (Intent-to-Treat Analysis)	Effect of MEDI-528 (30, 100, or 300 mg) versus placebo on the proportion of participants who had an AQLQ(S) assessment response at Day 176 (Intent-to-Treat Analysis). The AQLQ(S) is a 32-item questionnaire that measures the health related quality of life experienced by asthma patients. In the study, participants were asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score is calculated as the mean response to all questions. Individual improvement in the overall score of 0.5 has been identified as the minimally important difference, with score changes > 1.5 identified to be large meaningful differences.	Day 176	No
Secondary	Proportion of Participants With Detectable Anti-drug Antibodies to MEDI-528	Proportion of participants with detectable anti-drug antibodies to MEDI-528 in subjects receiving 30, 100, or 300 mg MEDI-528 and placebo	Days 1, 29, 57, 85, 127, 169, 176, 204,260, and 323	Yes
Secondary	First Dose Trough Concentration of MEDI-528	First dose trough concentration of MEDI-528 measured on Day 15 prior to administration of the second dose of MEDI-528 (30, 100, or 300 mg). Serum concentrations of MEDI-528 were measured on Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323. The first dose trough concentration of MEDI-528 was measured on Day 15 prior to the Day 15 dose.	Day 15	No
Secondary	Day 169 Steady State Trough Concentration of MEDI-528	Trough concentration of MEDI-528 measured on Day 169 prior to administration of the last dose of MEDI-528 (30, 100, or 300 mg). Serum concentrations of MEDI-528 were measured on Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323. Steady state trough concentration of MEDI-528 was measured on Day 169.	Day 169	No
Secondary	Half Life of MEDI-528	Half life of MEDI-528 in subjects receiving 30, 100, or 300 mg MEDI-528. Serum concentrations of MEDI-528 were measured on Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323.	Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323	No
Secondary	Accumulation Ratio of Trough Concentrations of MEDI-528	Accumulation ratio of trough concentrations of MEDI-528 in subjects receiving 30, 100, or 300 mg MEDI-528. Serum concentrations of MEDI-528 were measured on Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323.	Days 1, 15, 29, 57, 85, 127, 169, 176, 204, 232, 260, 288, and 323	No

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