A Two-Part Multicenter Prospective Longitudinal Study of CFTR-dependent Disease Profiling in Cystic Fibrosis (PROSPECT) (PROSPECT)
12 мая 2020 г. обновлено: Steven M Rowe, University of Alabama at Birmingham
identify and validate biomarkers that might reflect partial restoration of CFTR function and can be used to monitor disease progression, and ii) evaluate the mechanistic effects of CFTR modulators and other relevant therapies in individuals with CF
Обзор исследования
Подробное описание
Cystic fibrosis (CF) is a genetic disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein.
Over 1,900 mutations, categorized into five genotypic or functional classes are implicated in causing CF.
Severity of disease varies widely in CF based on CFTR-dependent and independent factors.
Progressive obstructive lung disease is the main determinant of morbidity and mortality in CF; therefore it is critical to identify biomarker profiles that reflect and predict this phenotypic variability, and understand their relationship to residual CFTR activity.
Emerging CFTR modulator therapies that directly target defective CFTR are being evaluated in pivotal clinical trials and may become available in the next few years.
It is not known how partial restoration of CFTR function might impact CF disease progression and disease-related biomarkers.
Thus there is urgent need to i) identify and validate biomarkers that might reflect partial restoration of CFTR function and can be used to monitor disease progression, and ii) evaluate the mechanistic effects of CFTR modulators and other relevant therapies in individuals with CF
Тип исследования
Наблюдательный
Регистрация (Действительный)
452
Контакты и местонахождение
В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.
Места учебы
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Alabama
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Birmingham, Alabama, Соединенные Штаты, 35233
- University of Alabama at Birmingham
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California
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Los Angeles, California, Соединенные Штаты, 90027
- Childrens Hospital Los Angeles
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Palo Alto, California, Соединенные Штаты, 94394
- Lucile S. Packard Children's Hospital
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Colorado
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Aurora, Colorado, Соединенные Штаты, 80045
- The Children's Hospital Colarado
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Denver, Colorado, Соединенные Штаты, 80206
- National Jewish Health
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Illinois
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Chicago, Illinois, Соединенные Штаты, 60611-2605
- Ann & Robert H. Lurie Children's Hospital of Chicago
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Indiana
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Indianapolis, Indiana, Соединенные Штаты
- Indianapolis University Hospital; James Whitcomb Riley Hospital for Children
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Kansas
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Kansas City, Kansas, Соединенные Штаты, 66160
- The University of Kansas Hospital
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Maryland
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Baltimore, Maryland, Соединенные Штаты, 21287
- John Hopkins University
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Massachusetts
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Boston, Massachusetts, Соединенные Штаты, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, Соединенные Штаты, 02115
- Children's Hospital Boston
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Michigan
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Detroit, Michigan, Соединенные Штаты, 48201
- Children's Hospital of Michigan
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Grand Rapids, Michigan, Соединенные Штаты, 49503
- Devon Children's Hospital at Spectrum Health
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Minnesota
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Minneapolis, Minnesota, Соединенные Штаты, 55455
- University of Minnesota
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Missouri
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Kansas City, Missouri, Соединенные Штаты, 64108
- Children's Mercy Hospital
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Saint Louis, Missouri, Соединенные Штаты, 63104
- Cardinal Glennon Children's Medical Center
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Saint Louis, Missouri, Соединенные Штаты
- St. Louis Children's Hospital
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New Hampshire
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Lebanon, New Hampshire, Соединенные Штаты
- Dartmouth Hitchcock Medical Center
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New York
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Buffalo, New York, Соединенные Штаты, 14222
- Women and Children's Hospital of Buffalo
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New York, New York, Соединенные Штаты, 10032
- Columbia University Medical Center
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Valhalla, New York, Соединенные Штаты, 10595
- Maria Fareri Children's Hospital; Westchester Medical Center
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North Carolina
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Chapel Hill, North Carolina, Соединенные Штаты, 27599
- University of North Carolina at Chapel Hill
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Ohio
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Akron, Ohio, Соединенные Штаты, 44308
- Akron Children's Hospital
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Cincinnati, Ohio, Соединенные Штаты, 45229
- Cincinnati Children's Hospital Medical Center
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Cleveland, Ohio, Соединенные Штаты, 44106
- University Hospital of Cleveland
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Columbus, Ohio, Соединенные Штаты
- Nation Wide Childrens Hospital
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Oregon
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Portland, Oregon, Соединенные Штаты, 97239
- Oregon Health & Sciences University
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Pennsylvania
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Hershey, Pennsylvania, Соединенные Штаты, 17033
- Hershey Medical Center; Penn State Children's Hospital
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Philadelphia, Pennsylvania, Соединенные Штаты
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Соединенные Штаты, 15213
- Children's Hospital of Pittsburgh of UPMC
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South Carolina
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Charleston, South Carolina, Соединенные Штаты, 29403
- Medical University of South Carolina
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Tennessee
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Nashville, Tennessee, Соединенные Штаты, 37232-9500
- The Children's Hospital at Vanderbilt
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Texas
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Houston, Texas, Соединенные Штаты, 77030
- Baylor College of Medicine/Texas Children's Hospital
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Utah
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Salt Lake City, Utah, Соединенные Штаты, 84132
- Primary Children's Hospital
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Washington
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Seattle, Washington, Соединенные Штаты, 98195
- University of Washington Medical Center
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Seattle, Washington, Соединенные Штаты, 98145-9807
- Seattle Children's Hospital
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Wisconsin
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Milwaukee, Wisconsin, Соединенные Штаты, 53226
- Froedtert Hospital
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Milwaukee, Wisconsin, Соединенные Штаты, 55455
- Children's Hospital of Wisconsin
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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
12 лет и старше (Ребенок, Взрослый, Пожилой взрослый)
Принимает здоровых добровольцев
Да
Полы, имеющие право на обучение
Все
Метод выборки
Вероятностная выборка
Исследуемая популяция
Part A N = 260 (210 CF, 50 non-CF controls)
- Cohort 1: 50 non-CF control subjects ≥ 12 years of age, with at least 15 subjects 12 - 21 yrs of age
- Cohort 2: 50 Partial CFTR Function CF subjects with at least one class IV/V CFTR mutation, ≥ 12 years of age
- Cohort 3 160 Absent CFTR Function CF subjects with two class I/II mutations ≥ 12 years of age
Part B
Up to 250 CF subjects who are homozygous for F508del mutation and who are prescribed ivacaftor/lumacafor for clinical care will be allowed to enroll. This will include :
- Cohort 3 subjects homozygous for F508del mutation from Part A who are prescribed ivacaftor/lumacaftor will be invited to participate in Part B (up to 100 potential subjects).
- Up to 150 additional CF subjects homozygous for F508del mutation ≥ 12 years of age who did not participate in Part A but are otherwise eligible for participation in Part B.
Описание
Inclusion Criteria Part A COHORT 1:
1. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.
2. Be willing and able to adhere to the study visit schedule and other protocol requirements 3. Male or female ≥ 12 years of age at Visit 1. 4. Have a body mass index (BMI) of:
- For subjects ≥ 18 years of age: ≤ 30 kg/m2
For subjects 12 - 17 years of age: ≤ 95th percentile 5. Be a non-smoker for ≥ 1 year at screening and have ≤ 10 pack-year history of smoking.
6. To participate in the optional DNA banking component of this study, subject must have signed the informed consent indicating willingness to participate in the genomic component of the study. Refusal to give consent for this component does not exclude a subject from participation in the study.
Inclusion Cohorts 2-3
- Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.
- Male or female ≥ 12 years of age at Visit 1.
Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and the following criteria: Cohort 2: (Partial Function CFTR CF)
Two mutations in the CFTR gene:
- At least one allele must be a Class IV or V mutation
- The second allele can be within any CFTR mutation class.
- Pancreatic sufficient (based on the absence of daily PERT use)
- At least one historic sweat chloride ≥60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT) OR sweat chloride results ≥ 40, but < 60mEQ/L upon permission of the PROSPECT Investigator-Sponsors.
Cohort 3: (Absent Function CF)
• Two class I or II CFTR mutations
- Enrolled in the Cystic Fibrosis Foundation Patient Registry. Patients may enroll in the Registry at Visit 1 if not previously enrolled.
- Clinically stable with no significant changes in health status within 2 weeks prior to Visit 1.
- Be a non-smoker for ≥ 1 year at screening and have ≤ 10 pack-year history of smoking.
- To participate in the optional DNA banking component of this study, subject must have signed the informed consent indicating willingness to participate in the genomic component of the study. Refusal to give consent for this component does not exclude a subject from participation in the study
Part B Inclusion
- Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.
- Physician decision to treat with ivacaftor/lumacaftor.
- Completion of at least Visit 1 and Visit 2 of Part A
Exclusion Criteria PART A COHORT 1
- Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
- A history of any clinically significant medical illness or medical disorder that requires ongoing systemic medical therapy, including (but not limited to) cardiovascular disease, neuromuscular disease, hematological disease including bleeding disorders, chronic respiratory disease (including persistent asthma), hepatic or gastrointestinal (GI) disease, neurological disease, neoplastic disease, renal diseases, or endocrine disorders including diabetes.
- Acute illness requiring any new prescription or over-the-counter treatment within 14 days prior to Visit 1.
- Major or traumatic surgery within 12 weeks prior to Visit 1.
- For females of child-bearing potential: a positive pregnancy test at Visit 1.
- Initiation of any new chronic therapy within 28 days prior to Visit 1.
- Use of an investigational agent within 28 days prior to Visit 1.
Exclusion Part A COHORTS 2-3
- Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
- Initiation of newly prescribed antibiotics [oral, intravenous (IV), and/or inhaled] for acute respiratory symptoms within 2 weeks of Visit 1.
- Major or traumatic surgery within 12 weeks prior to Visit 1.
- For females of child-bearing potential: a positive pregnancy test at Visit 1.
- Initiation of any new chronic therapy (e.g., ibuprofen Pulmozyme®, hypertonic saline, azithromycin, TOBI®, Cayston®) within 4 weeks prior to Visit 1.
- Use of an investigational agent within 28 days prior to Visit 1.
- Use of oral corticosteroids in doses exceeding 10 mg prednisone/day or 20 mg prednisone/every other day (subjects on oral steroids will be on stable doses for > 12 weeks prior to visit 1).
- Active treatment for nontuberculous mycobacterial (NTM) infection, consisting of ≥ two antibiotics (oral, IV, and/or inhaled).
- Use of CFTR modulator therapy such as ivacaftor (Kalydeco®) within 28 days prior to Visit 1.
- History of lung or liver transplantation, or listing for organ transplantation.
Exclusion PART B
- Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
- Initiation of newly prescribed antibiotics [oral, intravenous (IV), and/or inhaled] for acute respiratory symptoms within 2 weeks of Visit 4.
- Initiation of any new chronic therapy (e.g., ibuprofen, Pulmozyme®, hypertonic saline, azithromycin, TOBI®, Cayston®) within 4 weeks prior to Visit 4.
- Use of an investigational agent within 28 days prior to Visit 4.
- Use of oral corticosteroids in doses exceeding 10 mg prednisone/day or 20 mg prednisone/every other day (subjects on oral steroids will be on stable doses for > 12 weeks prior to Visit 4).
- Active treatment for nontuberculous mycobacterial (NTM) infection, consisting of ≥ two antibiotics (oral, IV, and/or inhaled).
- Use of CFTR modulator therapy such as ivacaftor (Kalydeco®) within 28 days prior to Visit 4.
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
Когорты и вмешательства
Группа / когорта |
Вмешательство/лечение |
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Part A
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Part B
CF patients who are homozygous for the F508del
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
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Sweat Chloride by Cohort (Part A Only)
Временное ограничение: For cohort 1, sweat chloride at Day 0 is time frame. For cohorts 2-3, sweat chloride averaged across all 3 visits at days 0, 14 and 90 is time frame.
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This is the primary endpoint for Part A per the PROSPECT protocol. Mean sweat chloride was not reported for Part B, as it is not a relevant statistic. For cohort 1, sweat chloride is from day 0 only. For cohorts 2-3, sweat chloride was averaged from days 0, 14, 90 via a random intercept longitudinal model. |
For cohort 1, sweat chloride at Day 0 is time frame. For cohorts 2-3, sweat chloride averaged across all 3 visits at days 0, 14 and 90 is time frame.
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6 Month Change in FEV1 Percent Predicted (Part B Only)
Временное ограничение: Baseline and 6 months
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This is the primary endpoint for Part B per the PROSPECT protocol.
Change in FEV1 Percent Predicted is only relevant for Part B as it captures changes in lung function post-initiation of Ivacaftor/Lumacaftor.
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Baseline and 6 months
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Соавторы и исследователи
Здесь вы найдете людей и организации, участвующие в этом исследовании.
Соавторы
Публикации и полезные ссылки
Лицо, ответственное за внесение сведений об исследовании, добровольно предоставляет эти публикации. Это может быть что угодно, связанное с исследованием.
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 марта 2015 г.
Первичное завершение (Действительный)
25 апреля 2018 г.
Завершение исследования (Действительный)
27 июля 2018 г.
Даты регистрации исследования
Первый отправленный
22 мая 2015 г.
Впервые представлено, что соответствует критериям контроля качества
19 июня 2015 г.
Первый опубликованный (Оценивать)
22 июня 2015 г.
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
20 мая 2020 г.
Последнее отправленное обновление, отвечающее критериям контроля качества
12 мая 2020 г.
Последняя проверка
1 мая 2020 г.
Дополнительная информация
Термины, связанные с этим исследованием
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
- PROSPECT
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. .