Cystic FibrosisPROSPECTNCT02477319
A Two-Part Multicenter Prospective Longitudinal Study of CFTR-dependent Disease Profiling in Cystic Fibrosis (PROSPECT)
An observational study of Cystic Fibrosis, run by University of Alabama at Birmingham at 38 sites in United States.
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 Read more about this study
- Who is it for?
- Ages 12 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Observational
- Type of treatment
- Injection or infusion
- How many people
- 452 participants
- Where
- 38 sitesUnited States
- Study dates
- Mar 2015to 27 Jul 2018
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: 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.
Who may be able to join
- 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.
- Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.
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- 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
Who cannot join
- 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.
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- Use of an investigational agent within 28 days prior to Visit 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.
- 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.
- 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.
Trial locations and contacts
38 sites in 1 country.
38 sites in 1 country
United States38 sites
Akron Children's Hospital
Akron, Ohio, 44308
The Children's Hospital Colarado
Aurora, Colorado, 80045
John Hopkins University
Baltimore, Maryland, 21287
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Massachusetts General Hospital
Boston, Massachusetts, 02114
Children's Hospital Boston
Boston, Massachusetts, 02115
Women and Children's Hospital of Buffalo
Buffalo, New York, 14222
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29403
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611-2605
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
University Hospital of Cleveland
Cleveland, Ohio, 44106
Nation Wide Childrens Hospital
Columbus, Ohio
National Jewish Health
Denver, Colorado, 80206
Children's Hospital of Michigan
Detroit, Michigan, 48201
Devon Children's Hospital at Spectrum Health
Grand Rapids, Michigan, 49503
Hershey Medical Center; Penn State Children's Hospital
Hershey, Pennsylvania, 17033
Baylor College of Medicine/Texas Children's Hospital
Houston, Texas, 77030
Indianapolis University Hospital; James Whitcomb Riley Hospital for Children
Indianapolis, Indiana
The University of Kansas Hospital
Kansas City, Kansas, 66160
Children's Mercy Hospital
Kansas City, Missouri, 64108
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire
Childrens Hospital Los Angeles
Los Angeles, California, 90027
Froedtert Hospital
Milwaukee, Wisconsin, 53226
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 55455
University of Minnesota
Minneapolis, Minnesota, 55455
The Children's Hospital at Vanderbilt
Nashville, Tennessee, 37232-9500
Columbia University Medical Center
New York, New York, 10032
Lucile S. Packard Children's Hospital
Palo Alto, California, 94394
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15213
Oregon Health & Sciences University
Portland, Oregon, 97239
Primary Children's Hospital
Salt Lake City, Utah, 84132
Seattle Children's Hospital
Seattle, Washington, 98145-9807
University of Washington Medical Center
Seattle, Washington, 98195
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
St. Louis Children's Hospital
St Louis, Missouri
Maria Fareri Children's Hospital; Westchester Medical Center
Valhalla, New York, 10595
About this study
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
Read the 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
- Being tested
- Observational
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ObservationalOther
| Study group | Role | What they receive |
|---|---|---|
| Part A | * Cohort 1: Healthy Controls
* Cohort 2: Partial CFTR function CF (class IV/V)
* Cohort 3: Absent CFTR function CF (Class I/II) Receives: Other: Observational | |
| Part B | CF patients who are homozygous for the F508del Receives: Other: Observational |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
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.
Measured: Baseline and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2015 (estimated)
- Study startMar 2015
- Primary completion25 Apr 2018
- Study completion27 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 452 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Cystic Fibrosis Foundation
- Responsible party
- Principal investigator, Steven M Rowe, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02477319
- Sponsor's protocol ID
- PROSPECT
- Acronym
- PROSPECT
- Status last verified
- May 2020
- First submitted
- 22 May 2015
- Last updated
- 20 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 32644818
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-Part Multicenter Prospective Longitudinal Study of CFTR-dependent Disease Profiling in Cystic Fibrosis (PROSPECT)
- ClinicalTrials.gov ID
- NCT02477319
- Acronym / sponsor ID
- PROSPECT / PROSPECT
- Conditions
- Cystic Fibrosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 452 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Cystic Fibrosis Foundation
- Study start
- Mar 2015
- Primary completion
- 25 Apr 2018 (actual)
- Study completion
- 27 Jul 2018 (actual)
- First posted
- 22 Jun 2015 (estimated)
- Results
- Posted 20 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part A | – | Other: Observational* Cohort 1: Healthy Controls * Cohort 2: Partial CFTR function CF (class IV/V) * Cohort 3: Absent CFTR function CF (Class I/II) |
| Part B | – | Other: ObservationalCF patients who are homozygous for the F508del |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- 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.
Key inclusion criteria (23 listed)
- 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:
- 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.
- 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.
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Observational | Other | Part A, Part B |
Primary outcome
Sweat Chloride by Cohort (Part A Only)
Time frame: 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.
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.
6 Month Change in FEV1 Percent Predicted (Part B Only)
Time frame: Baseline and 6 months
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32644818Sagel 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
38 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cystic Fibrosis, run by University of Alabama at Birmingham at 38 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sweat Chloride by Cohort (Part A Only) (time frame: 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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02477319, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2020.