A Two-Part Multicenter Prospective Longitudinal Study of CFTR-dependent Disease Profiling in Cystic Fibrosis (PROSPECT)

NCT ID: NCT02477319

Last Updated: 2020-05-20

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 452 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2018-07-27

Brief Summary

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

Detailed Description

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

Conditions

Cystic Fibrosis

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

Part A

• Cohort 1: Healthy Controls
• Cohort 2: Partial CFTR function CF (class IV/V)
• Cohort 3: Absent CFTR function CF (Class I/II)

Observational

Intervention Type: OTHER

Part B

CF patients who are homozygous for the F508del

Observational

Intervention Type: OTHER

Interventions

Observational

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

1. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.

2. Male or female ≥ 12 years of age at Visit 1.

3. 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

4. Enrolled in the Cystic Fibrosis Foundation Patient Registry. Patients may enroll in the Registry at Visit 1 if not previously enrolled.

5. Clinically stable with no significant changes in health status within 2 weeks prior to Visit 1.

6. Be a non-smoker for ≥ 1 year at screening and have ≤ 10 pack-year history of smoking.

7. 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

1. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.

2. Physician decision to treat with ivacaftor/lumacaftor.

3. Completion of at least Visit 1 and Visit 2 of Part A

Exclusion Criteria

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.

2. 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.

3. Acute illness requiring any new prescription or over-the-counter treatment within 14 days prior to Visit 1.

4. Major or traumatic surgery within 12 weeks prior to Visit 1.

5. For females of child-bearing potential: a positive pregnancy test at Visit 1.

6. Initiation of any new chronic therapy within 28 days prior to Visit 1.

7. Use of an investigational agent within 28 days prior to Visit 1.

Exclusion Part A COHORTS 2-3

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.

2. Initiation of newly prescribed antibiotics [oral, intravenous (IV), and/or inhaled] for acute respiratory symptoms within 2 weeks of Visit 1.

3. Major or traumatic surgery within 12 weeks prior to Visit 1.

4. For females of child-bearing potential: a positive pregnancy test at Visit 1.

5. Initiation of any new chronic therapy (e.g., ibuprofen Pulmozyme®, hypertonic saline, azithromycin, TOBI®, Cayston®) within 4 weeks prior to Visit 1.

6. Use of an investigational agent within 28 days prior to Visit 1.

7. 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).

8. Active treatment for nontuberculous mycobacterial (NTM) infection, consisting of ≥ two antibiotics (oral, IV, and/or inhaled).

9. Use of CFTR modulator therapy such as ivacaftor (Kalydeco®) within 28 days prior to Visit 1.

10. History of lung or liver transplantation, or listing for organ transplantation.

Exclusion PART B

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.

2. Initiation of newly prescribed antibiotics [oral, intravenous (IV), and/or inhaled] for acute respiratory symptoms within 2 weeks of Visit 4.

3. Initiation of any new chronic therapy (e.g., ibuprofen, Pulmozyme®, hypertonic saline, azithromycin, TOBI®, Cayston®) within 4 weeks prior to Visit 4.

4. Use of an investigational agent within 28 days prior to Visit 4.

5. 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).

6. Active treatment for nontuberculous mycobacterial (NTM) infection, consisting of ≥ two antibiotics (oral, IV, and/or inhaled).

7. Use of CFTR modulator therapy such as ivacaftor (Kalydeco®) within 28 days prior to Visit 4.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Cystic Fibrosis Foundation

OTHER

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Steven M Rowe

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Childrens Hospital Los Angeles

Los Angeles, California, United States

Lucile S. Packard Children's Hospital

Palo Alto, California, United States

The Children's Hospital Colarado

Aurora, Colorado, United States

National Jewish Health

Denver, Colorado, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Indianapolis University Hospital; James Whitcomb Riley Hospital for Children

Indianapolis, Indiana, United States

The University of Kansas Hospital

Kansas City, Kansas, United States

John Hopkins University

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Children's Hospital Boston

Boston, Massachusetts, United States

Children's Hospital of Michigan

Detroit, Michigan, United States

Devon Children's Hospital at Spectrum Health

Grand Rapids, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Children's Mercy Hospital

Kansas City, Missouri, United States

Cardinal Glennon Children's Medical Center

St Louis, Missouri, United States

St. Louis Children's Hospital

St Louis, Missouri, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Women and Children's Hospital of Buffalo

Buffalo, New York, United States

Columbia University Medical Center

New York, New York, United States

Maria Fareri Children's Hospital; Westchester Medical Center

Valhalla, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Akron Children's Hospital

Akron, Ohio, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

University Hospital of Cleveland

Cleveland, Ohio, United States

Nation Wide Childrens Hospital

Columbus, Ohio, United States

Oregon Health & Sciences University

Portland, Oregon, United States

Hershey Medical Center; Penn State Children's Hospital

Hershey, Pennsylvania, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

The Children's Hospital at Vanderbilt

Nashville, Tennessee, United States

Baylor College of Medicine/Texas Children's Hospital

Houston, Texas, United States

Primary Children's Hospital

Salt Lake City, Utah, United States

Seattle Children's Hospital

Seattle, Washington, United States

University of Washington Medical Center

Seattle, Washington, United States

Froedtert Hospital

Milwaukee, Wisconsin, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

Sagel SD, Khan U, Heltshe SL, Clancy JP, Borowitz D, Gelfond D, Donaldson SH, Moran A, Ratjen F, VanDalfsen JM, Rowe SM. Clinical Effectiveness of Lumacaftor/Ivacaftor in Patients with Cystic Fibrosis Homozygous for F508del-CFTR. A Clinical Trial. Ann Am Thorac Soc. 2021 Jan;18(1):75-83. doi: 10.1513/AnnalsATS.202002-144OC.

Reference Type: DERIVED

PMID: 32644818 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

PROSPECT

Identifier Type: -

Identifier Source: org_study_id