Cystic Fibrosis (CF)NCT03445793
: TRANSITION: An Observational Study of Transition From Lumacaftor/Ivacaftor to Tezacaftor/Ivacaftor (Tez/Iva)
An observational study of Cystic Fibrosis (CF), run by National Jewish Health at 1 site in United States.
Trial summary
This study is a single center study of clinical and laboratory outcomes in patients ≥ 12 who transition from use of Orkambi to tez/iva. Clinical and laboratory measurements will be measured at baseline, 1 month, 3 months, and 6 months after initiation of tez/iva. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Cystic Fibrosis (CF)
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2018to 1 Nov 2019
- 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
- No healthy volunteers
- Child, Adult, Older adult
Study population: Cystic fibrosis with 2 copies of F508del mutation.
Who may be able to join
- Confirmed diagnosis of CF
- Male or female subjects greater than or equal to 12 years of age
- Ability to reproducibly perform spirometry testing
- Physician decision to treat with tezacaftor/ivacaftor (Smydeko)
- Ability to understand and sign a written informed consent or assent and comply with the requirements of the study
- Continuous use of orkambi for at least 1 month prior to visit 1
Who cannot join
- History of hypersensitivity to tezacaftor and/or ivacaftor
- 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
- Any acute lower respiratory symptoms treated with oral, inhaled or intravenous antibiotics (IV) or systemic corticosteroids within the 2 weeks prior to Visit 1
- Major or traumatic surgery within 12 weeks prior to Visit 1
- For women of child-bearing potential: a positive pregnancy test at Visit 1
- Unable or unwilling to fast (including no enteric tube feedings) for at least 6 hours prior each visit
Show all 11Show fewer
- Initiation of any new chronic therapy within 4 weeks prior to Visit 1
- Use of an investigational agent within 28 days prior to Visit 1
- Use of chronic oral corticosteroids within 28 days prior to Visit 1
- Treatment for nontuberculous mycobacterial (NTM) infection, consisting of greater than or equal to two antibiotics (oral, IV, and/or inhaled) within 28 days prior to Visit 1
- History of lung or liver transplantation, or listing for organ transplantation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: : TRANSITION: An Observational Study of the Effects on Sweat Chloride and Clinical Outcomes of Transition From Lumacaftor/Ivacaftor to Tezacaftor/Ivacaftor (Tez/Iva)
This study is a single center study of clinical and laboratory outcomes in patients ≥ 12 who transition from use of Orkambi to tez/iva. Clinical and laboratory measurements will be measured at baseline, 1 month, 3 months, and 6 months after initiation of tez/iva. Change from baseline at 6 months pre-specified will be reported. The length of study participation will be approximately 6 months.
Read the detailed description
While cystic fibrosis (CF) therapeutic development previously targeted the signs and symptoms of the disease, in the last 5 years, two drugs that treat the basic defect in CF have been approved, ivacaftor (iva) and lumacaftor/ivacaftor (lum/iva). This class of drugs, deemed cystic fibrosis transmembrane conductance regulator (CFTR) modulators, variably improve CFTR function as measured by pilocarpine iontophoresis and sweat collection, and clinical outcomes including lung function, body mass index (BMI), rate of exacerbations and patient reported quality of life.
In patients with the G551D mutation who received iva, there was a marked decrease in sweat chloride and marked improvement in lung function as measured by absolute change from baseline of percent predicted expiratory volume in 1 second (ppFEV1). The clinical outcomes assessed in the phase III studies of lum/iva and tez/iva were similar, and included lung function, rate of pulmonary exacerbations, BMI, and CFQ-R scores. While the correlation between improvement in sweat chloride and lung function is poor, and a minimum threshold for change in sweat chloride that correlates with clinical outcomes has yet to be defined, it has also not been determined if an increase in sweat chloride caused by a transition from one drug to another would adversely impact clinical outcomes. Outcomes between the phase III studies of lum/iva and tez/iva were similar, tez/iva has three advantages that are likely to make it more appealing to patients and providers than lum/iva including positive clinical efficacy data, fewer drug-drug interactions, and an improved tolerance profile.
Following tez/iva approval, a rapid uptake of tez/iva for patients homozygous for F508del CFTR is expected; as a result of the transition from lum/iva to tez/iva, sweat chloride will increase possibly resulting in an adverse impact on clinical outcomes. This study aims to determine the rationale for patient transition from lum/iva to tez/iva, in addition to evaluate the impact of transition on CFTR function, pulmonary health, gastrointestinal health, and general health. While it is possible that there will be no change in sweat chloride or small changes that are without clinical significance, systematic collection of data as patients transition from lum/iva to tez/iva would permit rapid identification of any safety issues. Because the U.S. always leads the way with approval and reimbursement of new therapeutics, our experience with this transition will help guide its conduct for physicians and patients in the rest of the world.
- Conditions
- Cystic Fibrosis (CF)
- Keywords
- DeltaF508deletion (F508del) mutation in 2 copies
- Medical subject headings
- Cystic Fibrosis
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Sweat Chloride Concentration in Millimoles/Liter From Baseline at 6 Months Pre-specified to be Reported
Sweat chloride is a measure of cystic fibrosis transmembrane conductance regulator function. The calculations represent the average change from baseline to the average change at 6 months.
Measured: Baseline to 6 months
Secondary outcomes (9)
Rationale for Transition Per Physician Questionnaire
Questionnaire to determine the treating physician's reason for transition to tezacaftor/ivacaftor from lumacaftor/ivacaftor
Measured: 1 day (the questionnaire is done once at visit 1)
Rationale for Transition Per Subject Questionnaire
Questionnaire to determine the subject's reason for transition to tezacaftor/ivacaftor from lumacaftor/ivacaftor
Measured: 1 day (the questionnaire is done once at visit 1)
Pulmonary Exacerbations
Number of pulmonary exacerbations requiring oral or IV antibiotics
Measured: One year prior to study entry (time of consent) and during study participation
Change in Percent Predicted (ppFEV1) Value From Baseline at 6 Months Pre-specified to be Reported
Pulmonary function by spirometry, percent predicted forced expiratory volume in 1 second. The calculations represent the average change from baseline to the average change at 6 months.
Measured: Baseline to 6 months
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline at 6 Months
CF-related quality of life measure is a validated, CF specific, patient reported outcome (PRO). This portion of the PRO is specific to respiratory symptoms. The scaled score for each domain ranges from 0 (worst condition) to 100 (best condition), with higher scores indicating better health in respiratory domain.
Measured: Baseline to 6 months
Change in Weight in Kilograms From Baseline at 6 Months Pre-specified to be Reported
Weight is a reflection of nutrition status in CF and is expected to improve with CFTR modulation. The calculations represent the average change from baseline to the average change at 6 months.
Measured: Baseline to 6 months
Change in BMI in kg/m^2 From Baseline at 6 Months Pre-specified to be Reported
BMI is a reflection of nutrition status in CF and is expected to improve with CFTR modulation. The calculations represent the average change from baseline to the average change at 6 months.
Measured: Baseline to 6 months
Number of People With Undetectable or Normal Fecal Elastase Measurements at 6 Months Pre-specified to be Reported
Fecal elastase in micrograms/gram. Fecal elastase is a measure of pancreatic function: Less than 100 mcg/g indicates severe exocrine pancreatic insufficiency, 100-200 mcg/g indicates moderate to mild insufficiency, greater than 200 indicates normal pancreatic function. The count represents the number of participants with either an undetectable fecal elastase level or normal level at 6 months, indicating change in pancreatic function at 6 months.
Measured: 6 months
Change in Gastrointestinal Symptom Tracker Score From Baseline to 6 Months
The Exocrine Pancreatic Insufficiency (EPI) GI Symptom Tracker is meant to measure the impact treatment is having on GI symptoms, perceived by person completing the tracker. Participants answer 24 symptom questions on a scale from almost always to never (scale 4 to 1). Higher scores reflect more challenges/problems related to GI symptoms. For purposes of this outcome measure, subscales were combined to compute a total score (minimum score 24, maximum score 96). The difference of total scores from baseline at 6 months were calculated to measure average overall change in GI symptoms.
Measured: Baseline to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2018
- Study start1 Mar 2018
- Primary completion1 Nov 2019
- Study completion1 Nov 2019
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.
- Other trials for Cystic Fibrosis (CF)Studies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Jewish Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jennifer Taylor-Cousar, National Jewish Health
- Investigators
- Jennifer Taylor-Cousar, MD, MSCS, Principal investigator, National Jewish Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03445793
- Sponsor's protocol ID
- HS-3145
- Status last verified
- Jan 2024
- First submitted
- 5 Feb 2018
- Last updated
- 23 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- : TRANSITION: An Observational Study of the Effects on Sweat Chloride and Clinical Outcomes of Transition From Lumacaftor/Ivacaftor to Tezacaftor/Ivacaftor (Tez/Iva)
- ClinicalTrials.gov ID
- NCT03445793
- Acronym / sponsor ID
- HS-3145
- Conditions
- Cystic Fibrosis (CF)
- Keywords
- DeltaF508deletion (F508del) mutation in 2 copies
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- National Jewish HealthUniversity, hospital or other
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 1 Nov 2019 (actual)
- Study completion
- 1 Nov 2019 (actual)
- First posted
- 26 Feb 2018 (actual)
- Results
- Posted 1 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a single center study of clinical and laboratory outcomes in patients ≥ 12 who transition from use of Orkambi to tez/iva. Clinical and laboratory measurements will be measured at baseline, 1 month, 3 months, and 6 months after initiation of tez/iva. Change from baseline at 6 months pre-specified will be reported. The length of study participation will be approximately 6 months.
Detailed description
While cystic fibrosis (CF) therapeutic development previously targeted the signs and symptoms of the disease, in the last 5 years, two drugs that treat the basic defect in CF have been approved, ivacaftor (iva) and lumacaftor/ivacaftor (lum/iva). This class of drugs, deemed cystic fibrosis transmembrane conductance regulator (CFTR) modulators, variably improve CFTR function as measured by pilocarpine iontophoresis and sweat collection, and clinical outcomes including lung function, body mass index (BMI), rate of exacerbations and patient reported quality of life.
In patients with the G551D mutation who received iva, there was a marked decrease in sweat chloride and marked improvement in lung function as measured by absolute change from baseline of percent predicted expiratory volume in 1 second (ppFEV1). The clinical outcomes assessed in the phase III studies of lum/iva and tez/iva were similar, and included lung function, rate of pulmonary exacerbations, BMI, and CFQ-R scores. While the correlation between improvement in sweat chloride and lung function is poor, and a minimum threshold for change in sweat chloride that correlates with clinical outcomes has yet to be defined, it has also not been determined if an increase in sweat chloride caused by a transition from one drug to another would adversely impact clinical outcomes. Outcomes between the phase III studies of lum/iva and tez/iva were similar, tez/iva has three advantages that are likely to make it more appealing to patients and providers than lum/iva including positive clinical efficacy data, fewer drug-drug interactions, and an improved tolerance profile.
Following tez/iva approval, a rapid uptake of tez/iva for patients homozygous for F508del CFTR is expected; as a result of the transition from lum/iva to tez/iva, sweat chloride will increase possibly resulting in an adverse impact on clinical outcomes. This study aims to determine the rationale for patient transition from lum/iva to tez/iva, in addition to evaluate the impact of transition on CFTR function, pulmonary health, gastrointestinal health, and general health. While it is possible that there will be no change in sweat chloride or small changes that are without clinical significance, systematic collection of data as patients transition from lum/iva to tez/iva would permit rapid identification of any safety issues. Because the U.S. always leads the way with approval and reimbursement of new therapeutics, our experience with this transition will help guide its conduct for physicians and patients in the rest of the world.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Cystic fibrosis with 2 copies of F508del mutation.
Key inclusion criteria (6 listed)
- Confirmed diagnosis of CF
- Male or female subjects greater than or equal to 12 years of age
- Ability to reproducibly perform spirometry testing
- Physician decision to treat with tezacaftor/ivacaftor (Smydeko)
- Ability to understand and sign a written informed consent or assent and comply with the requirements of the study
Key exclusion criteria (11 listed)
- History of hypersensitivity to tezacaftor and/or ivacaftor
- 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
- Any acute lower respiratory symptoms treated with oral, inhaled or intravenous antibiotics (IV) or systemic corticosteroids within the 2 weeks prior to Visit 1
- Major or traumatic surgery within 12 weeks prior to Visit 1
- For women 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.
Primary outcome
Change in Sweat Chloride Concentration in Millimoles/Liter From Baseline at 6 Months Pre-specified to be Reported
Time frame: Baseline to 6 months
Sweat chloride is a measure of cystic fibrosis transmembrane conductance regulator function. The calculations represent the average change from baseline to the average change at 6 months.
9 secondary outcomes
Rationale for Transition Per Physician Questionnaire
Time frame: 1 day (the questionnaire is done once at visit 1)
Rationale for Transition Per Subject Questionnaire
Time frame: 1 day (the questionnaire is done once at visit 1)
Pulmonary Exacerbations
Time frame: One year prior to study entry (time of consent) and during study participation
Change in Percent Predicted (ppFEV1) Value From Baseline at 6 Months Pre-specified to be Reported
Time frame: Baseline to 6 months
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline at 6 Months
Time frame: Baseline to 6 months
Change in Weight in Kilograms From Baseline at 6 Months Pre-specified to be Reported
Time frame: Baseline to 6 months
Change in BMI in kg/m^2 From Baseline at 6 Months Pre-specified to be Reported
Time frame: Baseline to 6 months
Number of People With Undetectable or Normal Fecal Elastase Measurements at 6 Months Pre-specified to be Reported
Time frame: 6 months
Change in Gastrointestinal Symptom Tracker Score From Baseline to 6 Months
Time frame: Baseline to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Jennifer Taylor-Cousar, MD, MSCS principal investigator
National Jewish Health
1 site 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 (CF), run by National Jewish Health at 1 site 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 6 inclusion and 11 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 23 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 Oct 2021). 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?
Change in Sweat Chloride Concentration in Millimoles/Liter From Baseline at 6 Months Pre-specified to be Reported (time frame: Baseline to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Jan 2024.