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

Cystic Fibrosis Clinical Trial

— PROSPECT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02477319
• Other study ID #: PROSPECT
• Status: Completed
• Start date: March 2015
• Est. completion date: July 27, 2018

Study information

• Verified date: May 2020
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 452
• Est. completion date: July 27, 2018
• Est. primary completion date: April 25, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years and older

Eligibility

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

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 PART A COHORT 1

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Other:
• Observational

Locations

Country	Name	City	State
United States	Akron Children's Hospital	Akron	Ohio
United States	The Children's Hospital Colarado	Aurora	Colorado
United States	John Hopkins University	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Women and Children's Hospital of Buffalo	Buffalo	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
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	National Jewish Health	Denver	Colorado
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Devon Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Hershey Medical Center; Penn State Children's Hospital	Hershey	Pennsylvania
United States	Baylor College of Medicine/Texas Children's Hospital	Houston	Texas
United States	Indianapolis University Hospital; James Whitcomb Riley Hospital for Children	Indianapolis	Indiana
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	The University of Kansas Hospital	Kansas City	Kansas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Childrens Hospital Los Angeles	Los Angeles	California
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Froedtert Hospital	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	The Children's Hospital at Vanderbilt	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Lucile S. Packard Children's Hospital	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Oregon Health & Sciences University	Portland	Oregon
United States	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri
United States	St. Louis Children's Hospital	Saint Louis	Missouri
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	Maria Fareri Children's Hospital; Westchester Medical Center	Valhalla	New York

Sponsors (2)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	Cystic Fibrosis Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sweat Chloride by Cohort (Part A Only)	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.
Primary	6 Month Change in FEV1 Percent Predicted (Part B Only)	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.	Baseline and 6 months