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Study to Evaluate the Efficacy and Safety of MEDI-563 in Adults With Uncontrolled Asthma

28 сентября 2016 г. обновлено: MedImmune LLC

A Phase 2b, Dose-ranging Study to Evaluate the Efficacy and Safety of MEDI-563 in Adults With Uncontrolled Asthma

The primary objective of the study is to evaluate the effect of multiple-dose subcutaneous administrations of MEDI-563 on adults with uncontrolled asthma.

Обзор исследования

Статус

Завершенный

Условия

Вмешательство/лечение

Подробное описание

This is a Phase 2b, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of multiple-dose (7 doses) subcutaneous administration of benralizumab (MEDI-563) in adult subjects with uncontrolled asthma.

Тип исследования

Интервенционный

Регистрация (Действительный)

964

Фаза

  • Фаза 2

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Места учебы

  • Аргентина
      • Caba, Аргентина
        • Research Site
      • Ciudad de Buenos Aires, Аргентина
        • Research Site
      • Santa Fe, Аргентина
        • Research Site
      • Tucumán, Аргентина
        • Research Site
  • Болгария
      • Pleven, Болгария
        • Research Site
      • Ruse, Болгария
        • Research Site
      • Sofia, Болгария
        • Research Site
      • Troyan, Болгария
        • Research Site
  • Бразилия
      • Curitiba, Бразилия
        • Research Site
      • Florianópolis, Бразилия
        • Research Site
      • Juiz de Fora, Бразилия
        • Research Site
      • Porto Alegre, Бразилия
        • Research Site
      • Rio de Janeiro, Бразилия
        • Research Site
      • Salvador, Бразилия
        • Research Site
      • Santo André, Бразилия
        • Research Site
      • Sao Paulo, Бразилия
        • Research Site
      • São Paulo, Бразилия
        • Research Site
  • Канада
      • Quebec, Канада
        • Research Site
    • Ontario
      • Brampton, Ontario, Канада
        • Research Site
      • Toronto, Ontario, Канада
        • Research Site
    • Quebec
      • La Malbaie, Quebec, Канада
        • Research Site
  • Колумбия
      • Bogota, Колумбия
        • Research Site
      • Bogotá, Колумбия
        • Research Site
  • Мексика
      • Guadalajara, Мексика
        • Research Site
      • Mexico, Мексика
        • Research Site
      • Monterrey, Мексика
        • Research Site
      • Morelia, Мексика
        • Research Site
      • Villahermosa, Мексика
        • Research Site
      • Zapopan, Мексика
        • Research Site
  • Перу
      • Lima, Перу
        • Research Site
      • San Borja, Перу
        • Research Site
      • San Isidro, Перу
        • Research Site
      • Surco, Перу
        • Research Site
  • Польша
      • Białystok, Польша
        • Research Site
      • Bydgoszcz, Польша
        • Research Site
      • Lublin, Польша
        • Research Site
      • Ostrów Wielkopolski, Польша
        • Research Site
      • Pila, Польша
        • Research Site
      • Poznań, Польша
        • Research Site
      • Tarnów, Польша
        • Research Site
      • Warszawa, Польша
        • Research Site
      • Łódź, Польша
        • Research Site
  • Российская Федерация
      • Barnaul, Российская Федерация
        • Research Site
      • Chelyabinsk, Российская Федерация
        • Research Site
      • Ekaterinburg, Российская Федерация
        • Research Site
      • Kazan, Российская Федерация
        • Research Site
      • Moscow, Российская Федерация
        • Research Site
      • Novosibirsk, Российская Федерация
        • Research Site
      • Saint Petersburg, Российская Федерация
        • Research Site
      • Saint-Petersburg, Российская Федерация
        • Research Site
      • St-Petersburg, Российская Федерация
        • Research Site
  • Соединенные Штаты
    • Alabama
      • Birmingham, Alabama, Соединенные Штаты
        • Research Site
    • California
      • Los Angeles, California, Соединенные Штаты
        • Research Site
      • Orange, California, Соединенные Штаты
        • Research Site
      • San Diego, California, Соединенные Штаты
        • Research Site
      • Stockton, California, Соединенные Штаты
        • Research Site
    • Colorado
      • Colorado Springs, Colorado, Соединенные Штаты
        • Research Site
      • Denver, Colorado, Соединенные Штаты
        • Research Site
    • Connecticut
      • Waterbury, Connecticut, Соединенные Штаты
        • Research Site
    • Florida
      • Kissimmee, Florida, Соединенные Штаты
        • Research Site
      • Tampa, Florida, Соединенные Штаты
        • Research Site
    • Georgia
      • Stockbridge, Georgia, Соединенные Штаты
        • Research Site
    • Illinois
      • Normal, Illinois, Соединенные Штаты
        • Research Site
    • Maryland
      • Baltimore, Maryland, Соединенные Штаты
        • Research Site
    • Minnesota
      • Rochester, Minnesota, Соединенные Штаты
        • Research Site
    • Missouri
      • St Louis, Missouri, Соединенные Штаты
        • Research Site
      • St. Louis, Missouri, Соединенные Штаты
        • Research Site
    • Nebraska
      • Bellevue, Nebraska, Соединенные Штаты
        • Research Site
    • New Jersey
      • Summit, New Jersey, Соединенные Штаты
        • Research Site
    • New York
      • Rochester, New York, Соединенные Штаты
        • Research Site
    • North Carolina
      • Winston-Salem, North Carolina, Соединенные Штаты
        • Research Site
    • Ohio
      • Cincinnati, Ohio, Соединенные Штаты
        • Research Site
    • Oklahoma
      • Oklahoma City, Oklahoma, Соединенные Штаты
        • Research Site
    • Pennsylvania
      • Blue Bell, Pennsylvania, Соединенные Штаты
        • Research Site
      • Pittsburgh, Pennsylvania, Соединенные Штаты
        • Research Site
    • Rhode Island
      • Warwick, Rhode Island, Соединенные Штаты
        • Research Site
    • Texas
      • Boerne, Texas, Соединенные Штаты
        • Research Site
      • San Antonio, Texas, Соединенные Штаты
        • Research Site
    • Washington
      • Seattle, Washington, Соединенные Штаты
        • Research Site

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

От 18 лет до 75 лет (Взрослый, Пожилой взрослый)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Все

Описание

Inclusion Criteria:

  • Age 18 through 75 years at the time of screening
  • Adequate contraception from screening through end of trial
  • Weight of more than (>) 45 kilogram (kg) but less than or equal to (<=) 150 kg (>100 pound [lb] but <=330 lb)
  • History of physician-diagnosed asthma for at least 12 months prior to screening
  • Physician prescribed daily use of medium-dose or high-dose inhaled corticosteroid(s) (ICS) plus long-acting beta 2 agonist (LABA) for at least 12 months prior to screening
  • Willingness to switch to an ICS/LABA combination product
  • Dose of other asthma controller medications must be stable for at least 30 days prior to screening
  • At least 2 documented asthma exacerbations in the 12 months prior to screening that required use of a systemic corticosteroid burst
  • For subjects 65 years of age or older, a chest x-ray (CXR) or chest computed tomography (CT) that is normal for an asthmatic population
  • Ability and willingness to complete the study to Week 66, and if needed to Week 92.

Exclusion Criteria:

  • Known history of allergy or reaction to any component of the investigational product formulation
  • History of anaphylaxis to any biologic therapy
  • Unexplained diarrhea within 30 days prior to screening or diagnosis of helminth parasitic infestation within 6 months prior to screening
  • Use of immunosuppressive medication within 3 months prior to screening. Chronic oral prednisone or equivalent up to 10 milligram (mg) daily or 20 mg every other day for asthma is allowed
  • Oral corticosteroid burst or short-acting systemic corticosteroid within 30 days prior to screening or during the screening/run-in period
  • Acute upper or lower respiratory infections requiring antibiotics or antiviral medications within 30 days prior to the screening or during the screening/run-in period
  • Receipt of immunoglobulin or blood products within 30 days prior to screening
  • Receipt of any marketed or investigational biologic within 4 months or 5 half-lives prior to screening, whichever is longer
  • Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to screening, whichever is longer
  • Previously received MEDI-563
  • Any clinically relevant abnormal findings in physical examination
  • Past history of clinically significant cardiac disease or any electrocardiogram (ECG) abnormality
  • Breastfeeding or lactating women
  • History of alcohol or drug abuse within 12 months prior to screening
  • History of any known primary immunodeficiency disorder
  • Positive medical history for hepatitis B or C. Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to enrol
  • A positive human immunodeficiency virus (HIV) test or subject taking antiretroviral medications
  • History of cigarette smoking more than or equal to (>=) 10 pack-years or smoking within 12 months prior to screening.
  • Known exposure to inhaled occupational agents or fumes with an established diagnosis of occupational asthma
  • History of cancer, except for basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy >=12 months prior to screening or other malignancies treated with apparent success with curative therapy >=5 years prior to screening
  • Stable dose of allergy vaccination regimen for less than 30 days prior to screening
  • Subjects unable to demonstrate acceptable inhaler and peak flow meter techniques.

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Уход
  • Распределение: Рандомизированный
  • Интервенционная модель: Параллельное назначение
  • Маскировка: Двойной

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Плацебо Компаратор: Eosinophilic phenotype (EOS+) Placebo
EOS+ (defined as ELEN Index [proprietary mathematical algorithm to predict sputum eosinophil's greater than or equal to 2 percent] positive and/or FeNO [fraction of exhaled nitric oxide] greater than or equal to [>=] 50 parts per billion [ppb]) participants received matching placebo injections subcutaneous injection every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
Другой: Placebo
EOS+ and EOS- participants received two placebo injections subcutaneously.
Экспериментальный: EOS+ Benralizumab (2 mg)
EOS+ participants received single benralizumab 2 milligram (mg) injection subcutaneously every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
Биологический: Benralizumab 2 mg
EOS+ participants received single benralizumab 2 milligram (mg) injection followed by a single placebo injection subcutaneously.
Другие имена:
  • МЕДИ-563
Экспериментальный: EOS+ Benralizumab (20 mg)
EOS+ participants received single benralizumab 20 mg injection subcutaneously every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
Биологический: Benralizumab 20 mg
EOS+ participants received single benralizumab 20 mg injection followed by a single placebo injection subcutaneously.
Другие имена:
  • МЕДИ-563
Экспериментальный: EOS+ Benralizumab (100 mg)
EOS+ participants received benralizumab 50 mg as two injections subcutaneously every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
Биологический: Benralizumab 100 mg
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
Другие имена:
  • МЕДИ-563
Плацебо Компаратор: Non-eosinophil phenotype (EOS-) Placebo
EOS- (defined as ELEN Index negative and FeNO <50 ppb) participants received matching placebo subcutaneous every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
Другой: Placebo
EOS+ and EOS- participants received two placebo injections subcutaneously.
Экспериментальный: EOS- Benralizumab (100 mg)
EOS- participants received benralizumab 50 mg as two injections subcutaneously every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
Биологический: Benralizumab 100 mg
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
Другие имена:
  • МЕДИ-563

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Annual Asthma Exacerbation Rate (AER) for Eosinophilic Phenotype (EOS+) Participants
Временное ограничение: Week 1 up to Week 52
The annual asthma exacerbation rate (AER) was calculated as the total number of observed exacerbations in each group up to week 52, divided by total duration of person-year follow-up in each group. An asthma exacerbation is defined as a progressive increase of asthma symptoms (cough, wheeze, chest tightness, and/or shortness of breath) that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 days as prescribed or administered by the investigator or healthcare provider; or 2) participant initiation of systemic corticosteroids (tablets, suspension or injection) for a duration of at least 3 days as outlined in the Asthma Action Plan provided to the participant by the investigator on Day 1.
Week 1 up to Week 52

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Dose Response in EOS+ Participants
Временное ограничение: Baseline up to Week 66
Baseline up to Week 66
Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ss)
Временное ограничение: Pre-dose (0 hour), Post-dose on Day 1, 6, Week 4, 16, 24, 32, 40, and 52
Pre-dose (0 hour), Post-dose on Day 1, 6, Week 4, 16, 24, 32, 40, and 52
Dose-Normalized Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ssD)
Временное ограничение: Pre-dose (0 hour), Post-dose on Day 1, 6, Week 4, 16, 24, 32, 40, and 52
Pre-dose (0 hour), Post-dose on Day 1, 6, Week 4, 16, 24, 32, 40, and 52
Percentage of Participants With Anti-Drug Antibodies (ADA) to Benralizumab in Eosinophilic Phenotype (EOS+) Participants
Временное ограничение: Baseline up to Week 92
Immunogenicity assessment included determination of anti-drug (benralizumab) antibodies in serum samples. ADA positive was defined as a titer >=50 at any point in the study. It was observed at baseline and any visit during the study.
Baseline up to Week 92
Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52
Временное ограничение: Baseline up to Week 52
Asthma Control Questionnaire (ACQ) is a participant-reported questionnaire to assess the asthma control with 6 items assessing night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Each item was rated on a 7-point Likert scale ranging from 0 (no impairment) to 6 (maximum impairment). Overall ACQ score was the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Data collected on Day 1 prior to dosing was considered as baseline. Results were reported for overall ACQ score. ACQ-6 score was summarized together for all participants.
Baseline up to Week 52
Change From Baseline in Mean Total Nasal Symptoms Score (TNSS) at Week 52
Временное ограничение: Baseline up to Week 52
Total Nasal Symptoms Score (TNSS) is a 3-item questionnaire, the sum of nasal symptoms, namely, nasal obstruction (rhinorrhea), nasal congestion, and nasal itching/sneezing. Each symptom was rated on a scale from 0-3, with 0 representing no symptoms, 1 mild, 2 moderate, and 3 severe symptoms. TNSS score was a summation of the 3 individual nasal symptom. TNSS score could range from 0 to 9 where higher score indicates worsening. Data was summarized by each treatment group. In addition, data was summarized together for "EOS+ and EOS- Placebo" arms and "EOS+ and EOS- benralizumab 100 mg" arms.
Baseline up to Week 52
Change From Baseline in Mean Asthma Symptom Diary Score at Week 51-52
Временное ограничение: Baseline up to Week 51-52
Asthma Symptom Diary included 7 questions about the participant symptom and the overall impact of treatment on the disease during the study period. Mean scores of the 7 questions were calculated to identify asthma symptom-free days. Asthma Symptom Diary Scores were analyzed on a bi-weekly basis and compared to baseline scores. Overall symptom score=(daytime frequency score + daytime severity score + nighttime severity score)/3, where total score ranges from 0 to 9. Higher score represents worsening. Mean asthma symptom diary score were summarized together for all participants. Mean asthma symptom diary score were summarized together for all participants. In addition, data was summarized together for "EOS+ and EOS- Placebo" arms and "EOS+ and EOS- benralizumab 100 mg" arms.
Baseline up to Week 51-52
Change From Baseline in Rescue Medication Use at Week 51-52
Временное ограничение: Baseline up to Week 51-52
Participants were provided inhalers of the same dose (medium- or high-dose) inhaled corticosteroid (ICS) plus long-acting beta antagonist (LABA) combination product as baseline prophylactic medication and continued with same dose throughout the study. Rescue medications such as short-term beta2 agonists were used as first-line treatment for worsening asthma symptoms. Investigator prescribed additional short term asthma controller medications included additional ICS, theophylline, inhaled cromones or antimuscarinics; if asthma symptoms remained mild but not resolved. If asthma symptoms worsened, participants received an oral corticosteroid burst. All rescue medications use with prophylactic medication (+ prophylactic) and without prophylactic medication (- prophylactic) was recorded in asthma symptom dairy by participant. Rescue medication use was analyzed on a bi-weekly basis and compared to baseline scores.
Baseline up to Week 51-52
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 52
Временное ограничение: Baseline and Week 52
FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data was summarized by each treatment group. In addition, data was summarized together for "EOS+ and EOS- Placebo" arms and "EOS+ and EOS- benralizumab 100 mg" arms.
Baseline and Week 52
Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52
Временное ограничение: Baseline and Week 52
Forced Vital Capacity (FVC) was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.
Baseline and Week 52
Change From Baseline in Peak Expiratory Flow (PEF) at Week 52
Временное ограничение: Baseline and Week 52
The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed while sitting or standing prior to using any medication (if needed) for asthma. Home PEF was determined separately for morning and evening, and were averaged for each participant. Data was summarized by each treatment group. In addition, data was summarized together for "EOS+ and EOS- Placebo" arms and "EOS+ and EOS- benralizumab 100 mg" arms.
Baseline and Week 52
Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Score at Week 52
Временное ограничение: Baseline and Week 52
AQLQ: a 32-item questionnaire evaluating quality of life of participants with asthma including 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). 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 was calculated as the mean response to all questions. The 4 domain scores were the means of the responses to the questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment). The AQLQ(S) responses were categorized as improvement (defined as change from baseline >=0.5), no change (defined as change from baseline >= -0.5 to less than [<] 0.5), and worse (defined as change from baseline < -0.5). Data was summarized by each treatment group.
Baseline and Week 52
Change From Baseline in European Quality of Life - 5 Dimensions (EQ-5D) Health State Evaluation at Week 52
Временное ограничение: Baseline and Week 52
The utility-based EQ-5D questionnaire comprises of two parts and provides a generic measure of health for clinical and economic appraisal. The health state valuation was the summary score of mobility, self-care, usual activities, pain/discomfort and anxiety/depression on a 3 category scale (no problem, moderate problem, severe problems). Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. Data was summarized by each treatment group. In addition, data was summarized together for "EOS+ and EOS- Placebo" arms and "EOS+ and EOS- benralizumab 100 mg" arms.
Baseline and Week 52
Change From Baseline in EQ-5D Visual Analog Scale (VAS) at Week 52
Временное ограничение: Baseline and Week 52
The utility-based EQ-5D questionnaire comprises of two parts and provides a generic measure of health for clinical and economic appraisal. The EQ-5D VAS was measured from 0 (worst imaginable health state) to 100 (best imaginable health state). Data was summarized by each treatment group. In addition, data was summarized together for "EOS+ and EOS- Placebo" arms and "EOS+ and EOS- benralizumab 100 mg" arms.
Baseline and Week 52
Change From Baseline in Percentage of Nocturnal Awakening-Free Nights at Week 51-52
Временное ограничение: Baseline up to Week 51-52
Percentage of nocturnal awakening-free nights were analyzed on a bi-weekly basis and compared to baseline scores. Data was summarized by each treatment group. In addition, data was summarized together for "EOS+ and EOS- Placebo" arms and "EOS+ and EOS- benralizumab 100 mg" arms.
Baseline up to Week 51-52
Change From Baseline in Mean Fraction Exhaled Nitric Oxide (FeNO) at Week 52
Временное ограничение: Baseline up to Week 52
Data was summarized by each treatment group. In addition, data was summarized together for "EOS+ and EOS- Placebo" arms and "EOS+ and EOS- benralizumab 100 mg" arms.
Baseline up to Week 52

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

MedImmune LLC

Соавторы

MedImmune Ltd

Следователи

  • Директор по исследованиям: Donald Raible, MD, MedImmune LLC

Публикации и полезные ссылки

Лицо, ответственное за внесение сведений об исследовании, добровольно предоставляет эти публикации. Это может быть что угодно, связанное с исследованием.

Общие публикации

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования

1 декабря 2010 г.

Первичное завершение (Действительный)

1 марта 2013 г.

Завершение исследования (Действительный)

1 августа 2013 г.

Даты регистрации исследования

Первый отправленный

9 ноября 2010 г.

Впервые представлено, что соответствует критериям контроля качества

9 ноября 2010 г.

Первый опубликованный (Оценивать)

11 ноября 2010 г.

Обновления учебных записей

Последнее опубликованное обновление (Оценивать)

17 ноября 2016 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

28 сентября 2016 г.

Последняя проверка

1 сентября 2016 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • MI-CP220
  • 2010-020126-17 (Номер EudraCT)

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

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