A Two-Part Multicenter Prospective Longitudinal Study of CFTR-dependent Disease Profiling in Cystic Fibrosis (PROSPECT) (PROSPECT)
12 de maio de 2020 atualizado por: 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
Visão geral do estudo
Descrição detalhada
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
Tipo de estudo
Observacional
Inscrição (Real)
452
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Alabama
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Birmingham, Alabama, Estados Unidos, 35233
- University of Alabama at Birmingham
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California
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Los Angeles, California, Estados Unidos, 90027
- Childrens Hospital Los Angeles
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Palo Alto, California, Estados Unidos, 94394
- Lucile S. Packard Children's Hospital
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Colorado
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Aurora, Colorado, Estados Unidos, 80045
- The Children's Hospital Colarado
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Denver, Colorado, Estados Unidos, 80206
- National Jewish Health
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Illinois
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Chicago, Illinois, Estados Unidos, 60611-2605
- Ann & Robert H. Lurie Children's Hospital of Chicago
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Indiana
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Indianapolis, Indiana, Estados Unidos
- Indianapolis University Hospital; James Whitcomb Riley Hospital for Children
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Kansas
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Kansas City, Kansas, Estados Unidos, 66160
- The University of Kansas Hospital
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Maryland
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Baltimore, Maryland, Estados Unidos, 21287
- John Hopkins University
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, Estados Unidos, 02115
- Children's Hospital Boston
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Michigan
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Detroit, Michigan, Estados Unidos, 48201
- Children's Hospital of Michigan
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Grand Rapids, Michigan, Estados Unidos, 49503
- Devon Children's Hospital at Spectrum Health
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Minnesota
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Minneapolis, Minnesota, Estados Unidos, 55455
- University of Minnesota
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Missouri
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Kansas City, Missouri, Estados Unidos, 64108
- Children's Mercy Hospital
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Saint Louis, Missouri, Estados Unidos, 63104
- Cardinal Glennon Children's Medical Center
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Saint Louis, Missouri, Estados Unidos
- St. Louis Children's Hospital
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New Hampshire
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Lebanon, New Hampshire, Estados Unidos
- Dartmouth Hitchcock Medical Center
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New York
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Buffalo, New York, Estados Unidos, 14222
- Women and Children's Hospital of Buffalo
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New York, New York, Estados Unidos, 10032
- Columbia University Medical Center
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Valhalla, New York, Estados Unidos, 10595
- Maria Fareri Children's Hospital; Westchester Medical Center
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North Carolina
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Chapel Hill, North Carolina, Estados Unidos, 27599
- University of North Carolina at Chapel Hill
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Ohio
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Akron, Ohio, Estados Unidos, 44308
- Akron Children's Hospital
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Cincinnati, Ohio, Estados Unidos, 45229
- Cincinnati Children's Hospital Medical Center
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Cleveland, Ohio, Estados Unidos, 44106
- University Hospital of Cleveland
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Columbus, Ohio, Estados Unidos
- Nation Wide Childrens Hospital
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Oregon
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Portland, Oregon, Estados Unidos, 97239
- Oregon Health & Sciences University
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Pennsylvania
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Hershey, Pennsylvania, Estados Unidos, 17033
- Hershey Medical Center; Penn State Children's Hospital
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Philadelphia, Pennsylvania, Estados Unidos
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Estados Unidos, 15213
- Children's Hospital of Pittsburgh of UPMC
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South Carolina
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Charleston, South Carolina, Estados Unidos, 29403
- Medical University of South Carolina
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37232-9500
- The Children's Hospital at Vanderbilt
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Texas
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Houston, Texas, Estados Unidos, 77030
- Baylor College of Medicine/Texas Children's Hospital
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Utah
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Salt Lake City, Utah, Estados Unidos, 84132
- Primary Children's Hospital
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Washington
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Seattle, Washington, Estados Unidos, 98195
- University of Washington Medical Center
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Seattle, Washington, Estados Unidos, 98145-9807
- Seattle Children's Hospital
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Wisconsin
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Milwaukee, Wisconsin, Estados Unidos, 53226
- Froedtert Hospital
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Milwaukee, Wisconsin, Estados Unidos, 55455
- Children's Hospital of Wisconsin
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
12 anos e mais velhos (Filho, Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Sim
Gêneros Elegíveis para o Estudo
Tudo
Método de amostragem
Amostra de Probabilidade
População do estudo
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.
Descrição
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.
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
Coortes e Intervenções
Grupo / Coorte |
Intervenção / Tratamento |
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Part A
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Part B
CF patients who are homozygous for the F508del
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Sweat Chloride by Cohort (Part A Only)
Prazo: 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)
Prazo: 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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Colaboradores e Investigadores
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Patrocinador
Colaboradores
Publicações e links úteis
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Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de março de 2015
Conclusão Primária (Real)
25 de abril de 2018
Conclusão do estudo (Real)
27 de julho de 2018
Datas de inscrição no estudo
Enviado pela primeira vez
22 de maio de 2015
Enviado pela primeira vez que atendeu aos critérios de CQ
19 de junho de 2015
Primeira postagem (Estimativa)
22 de junho de 2015
Atualizações de registro de estudo
Última Atualização Postada (Real)
20 de maio de 2020
Última atualização enviada que atendeu aos critérios de controle de qualidade
12 de maio de 2020
Última verificação
1 de maio de 2020
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- PROSPECT
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .