Cystic Fibrosis
Conditions
Keywords
Cystic Fibrosis, CF, Withdrawal, ETI, hypertonic saline, discontinue
Brief summary
Despite the increasingly common use of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies in treating cystic fibrosis (CF), it is still largely unknown whether or not other chronic therapies can be safely stopped. This SIMPLIFY sub-study is being done to test whether or not it is safe to stop taking inhaled hypertonic saline in those people that are also taking elexacaftor/tezacaftor/ivacaftor (ETI). ETI is a combination CFTR modulator therapy that was approved by the Food and Drug Administration for people with CF who have at least one F508del mutation. The three drugs that make up ETI work together to allow many more chloride ions to move into and out of the cells, improving the balance of salt and water in the lungs. These changes result in better clearance of mucus from the lungs and improvements in lung function. Inhaled hypertonic saline (HS) also improves clearance of mucus from the lungs to support lung function and has been available to people with CF for many years. HS is considered to be relatively burdensome and it is not known whether HS can improve or maintain lung function above what is already gained through ETI use. The goal of this SIMPLIFY sub-study is to get information about whether or not it is safe to stop hypertonic saline by testing if there is a change in lung function in participants with cystic fibrosis (CF) who are assigned to stop taking HS as compared to those who are assigned to keep taking HS while continuing to take ETI. This is a sub study of master protocol SIMPLIFY-IP-19, NCT04378153. The sub study investigating the impact of discontinuing and continuing dornase alfa is registered under NCTXXXXXXX (will add once available).
Detailed description
This SIMPLIFY sub-study (Hypertonic Saline (HS) Trial) is designed to evaluate the effects of discontinuing HS in people with cystic fibrosis (CF) age 12 and older currently taking the highly effective modulator elexacaftor/tezacaftor/ivacaftor (ETI). This is an open label two-arm randomized non-inferiority trial consisting of a 2-week screening period, randomization to continue or discontinue hypertonic saline, followed by a 6-week study period. Participants at trial entry will be randomized 1:1 to either continue or discontinue their HS therapy. Clinical outcomes (forced expiratory volume in 1 second \[FEV1\], antibiotic use, pulmonary exacerbations, and patient reported outcomes), safety (adverse events) and patient reported outcomes to evaluate respiratory symptoms and the participant's perception of how stopping HS would impact their daily life will be evaluated in all subjects. Additionally, a subset of participants at selected study sites will participate in Multiple Breath Washout (MBW) to evaluate changes in lung clearance index (LCI).
Interventions
OTHERDiscontinuation of hypertonic saline (HS)
Discontinuation of current hypertonic saline (HS) therapy during 6-week study period.
OTHERContinuation of hypertonic saline (HS)
Continuation of current hypertonic saline (HS) therapy during 6-week study period. Therapy is taken at least once daily according to each participant's pre-existing, clinically prescribed regimen (e.g., daily, twice daily). The concentration of HS is according to clinical prescription (e.g., 7% sodium chloride or 3.5% sodium chloride) and at least 3%.
Sponsors
Cystic Fibrosis Foundation
Dartmouth-Hitchcock Medical Center
University of Washington
Nicole Hamblett
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of CF. * Age ≥ 12 years at the Screening Visit. * Forced expiratory volume in 1 second (FEV1) ≥ 70 % predicted at the Screening Visit if \< 18 years old, and ≥ 60 % predicted at Screening Visit if ≥ 18 years old. * Clinically stable with no significant changes in health status within the 7 days prior to and including the Screening Visit. * Current treatment with elexacaftor/tezacaftor/ivacaftor (ETI) for at least the 90 days prior to and including the Screening Visit and willing to continue daily use for the duration of the study. * Currently taking hypertonic saline (at least 3%) for at least the 90 days prior to and including the Screening Visit and willing to continue daily use for the 2-week screening period.
Exclusion criteria
* Active smoking or vaping. * Use of an investigational drug within 28 days prior to and including the Screening Visit. * Changes to chronic therapy (e.g., ibuprofen, azithromycin, inhaled tobramycin, aztreonam lysine) within 28 days prior to and including the Screening Visit. This includes new airway clearance routines. * Acute use of antibiotics (oral, inhaled or IV) or acute use of systemic corticosteroids for respiratory tract symptoms within 7 days prior to and including the Screening Visit. * Chronic use of systemic corticosteroids at a dose equivalent to ≥ 10mg per day of prednisone within 28 days prior to and including the Screening Visit. * Antibiotic treatment for nontuberculous mycobacteria (NTM) within 28 days prior to and including the Screening Visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in FEV1 % Predicted From Week 0 to Week 6 | Week 0 to Week 6 | Difference between study arms (discontinue - continue) in the absolute change in FEV1 % predicted from Week 0 to Week 6. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in Respiratory Symptoms, as Measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) From Week 0 to Week 6 | Week 0 to Week 6 | Difference between study arms (discontinue - continue) in the absolute change in respiratory symptoms, as measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) from Week 0 to Week 6. The Cystic Fibrosis Respiratory Symptoms Daily Diary (CFRSD) asks a participant to state the extent of their 8 respiratory symptoms: difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the response, with zero corresponding to the absence of the symptom and four corresponding to symptom being present 'a great deal' or 'extremely'. A summed score (range from 0-24) is calculated for each participant and converted to a final score with a range of 0 to 100, where the lowest scores indicate improvement of symptoms. Calculation of a score requires responses for at least 7 out of 8 symptoms. |
| Absolute Change in Respiratory Symptoms, as Measured by CFQ-R Respiratory Domain From Week 0 to Week 6 | Week 0 to Week 6 | Difference between study arms (discontinue - continue) in the absolute change in respiratory symptoms, as measured by the Cystic Fibrosis Questionnaire-Revised Respiratory Domain Score from Week 0 to Week 6. The Cystic Fibrosis Questionnaire - Revised asks participants 6 questions related to respiratory symptoms which are each assigned a score 1-4. The Respiratory Domain Scaled Score is calculated as follows: 100\*\[{sum of responses}/{number of responses}-1\]/3 only if number of responses ≥ 3; otherwise the score is set to missing. The scaled score ranges from 0 to 100 where higher scores indicate improvement of symptoms. |
| Absolute Change in FEV1 % Predicted From Week -2 to Week 0 | Week -2 to Week 0 | Difference between study arms (discontinue - continue) in the absolute change in FEV1 % predicted from Week -2 to Week 0. |
| Absolute Change in FEV1 % Predicted From Week 0 to Week 2 | Week 0 to Week 2 | Difference between study arms (discontinue - continue) in the absolute change in FEV1 % predicted from Week 0 to Week 2. |
| Number and Percent of Participants Initiating Acute Antibiotics From Week 0 to Week 6 | Week 0 to Week 6 | Difference between study arms (discontinue - continue) in the percent of subjects initiating acute oral, inhaled or intravenous antibiotics from Week 0 to Week 6. Includes antibiotics initiated for respiratory indications; excludes those taken as part of a chronic cycled regimen or for a UTI, skin infection, etc. |
| Absolute Change in LCI 2.5 From Baseline to Week 6 | Baseline (Week 0 or Week -2) to Week 6 | Difference between study arms (discontinue - continue) in the absolute change in LCI 2.5 (Lung Clearance Index) from Baseline (Week 0, if available, or else Week -2) to Week 6. LCI 2.5 is the number of times the volume in the lungs needs to turn over to expel an inert gas. A higher value of LCI 2.5 indicates poorer lung function. |
| Number and Percent of Participants Experiencing Pulmonary Exacerbations From Week 0 to Week 6 | Week 0 to Week 6 | Difference between study arms (discontinue - continue) in the percent of subjects experiencing a pulmonary exacerbation from Week 0 to Week 6. Pulmonary exacerbations defined using Fuchs criteria. |
| Number and Percent of Participants Experiencing Adverse Events (AEs) From Week 0 to Week 6 | Week 0 to Week 6 | Difference between study arms (discontinue - continue) in the percent of participants with at least one AE from Week 0 to Week 6. Includes serious and non-serious AEs. |
| Rate of Adverse Events (AEs) From Week 0 to Week 6 Therapy Arms | Week 0 to Week 6 | Comparison of study arms (discontinue/continue) in the rate of AE occurrence (number of events divided by total follow-up weeks in each arm) from Week 0 to Week 6. Includes serious and non-serious AEs. |
| Number and Percent of Participants With Temporary or Permanent Changes From Assigned Therapy Regimen Due to Adverse Event From Week 0 to Week 6 | Week 0 to Week 6 | Difference between study arms (discontinue - continue) in the percent of subjects temporarily or permanently changing their assigned therapy regimen due to an adverse event Week 0 to Week 6 |
| Number and Percent of Participants Hospitalized From Week 0 to Week 6 | Week 0 to Week 6 | Difference between study arms (discontinue - continue) in the percent of subjects hospitalized from Week 0 to Week 6. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HS-Discontinue Discontinuation of current hypertonic saline (HS) therapy
Discontinuation of hypertonic saline (HS): Discontinuation of current hypertonic saline (HS) therapy during 6-week study period. | 133 |
| HS-Continue Continuation of current hypertonic saline (HS) therapy
Continuation of hypertonic saline (HS): Continuation of current hypertonic saline (HS) therapy during 6-week study period. Therapy is taken at least once daily according to each participant's pre-existing, clinically prescribed regimen (e.g., daily, twice daily). The concentration of HS is according to clinical prescription (e.g., 7% sodium chloride or 3.5% sodium chloride) and at least 3%. | 140 |
| Total | 273 |
Baseline characteristics
| Characteristic | HS-Continue | HS-Discontinue | Total |
|---|---|---|---|
| Age, Continuous | 23.5 years STANDARD_DEVIATION 11.34 | 21.8 years STANDARD_DEVIATION 11.06 | 22.7 years STANDARD_DEVIATION 11.22 |
| Age, Customized Age Distribution (years) >=12 to 18 | 64 Participants | 68 Participants | 132 Participants |
| Age, Customized Age Distribution (years) >=18 to <24 | 28 Participants | 24 Participants | 52 Participants |
| Age, Customized Age Distribution (years) >=24 to <30 | 15 Participants | 22 Participants | 37 Participants |
| Age, Customized Age Distribution (years) >=30 | 33 Participants | 19 Participants | 52 Participants |
| Current Airway Clearance Use | 132 Participants | 127 Participants | 259 Participants |
| Current Dornase Alfa Use | 120 Participants | 111 Participants | 231 Participants |
| Cystic Fibrosis (CF) Genotype F508 Heterozygous | 53 Participants | 51 Participants | 104 Participants |
| Cystic Fibrosis (CF) Genotype F508 Homozygous | 84 Participants | 82 Participants | 166 Participants |
| Cystic Fibrosis (CF) Genotype Other or Unknown | 3 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 11 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 134 Participants | 122 Participants | 256 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| FEV1 (% Predicted) | 96.8 Percent of Predicted STANDARD_DEVIATION 17.3 | 97.6 Percent of Predicted STANDARD_DEVIATION 17.55 | 97.2 Percent of Predicted STANDARD_DEVIATION 17.4 |
| FEV1 (% Predicted) Distribution >=100 | 66 Participants | 60 Participants | 126 Participants |
| FEV1 (% Predicted) Distribution <60 | 1 Participants | 1 Participants | 2 Participants |
| FEV1 (% Predicted) Distribution >=60 to <70 | 10 Participants | 9 Participants | 19 Participants |
| FEV1 (% Predicted) Distribution >=70 to <90 | 37 Participants | 32 Participants | 69 Participants |
| FEV1 (% Predicted) Distribution >=90 to <100 | 26 Participants | 31 Participants | 57 Participants |
| Forced Expiratory Volume in 1 second (FEV1) | 3.4 Liters STANDARD_DEVIATION 0.89 | 3.4 Liters STANDARD_DEVIATION 0.91 | 3.4 Liters STANDARD_DEVIATION 0.9 |
| Previous Enrollment in SIMPLIFY-DA Study No | 95 Participants | 91 Participants | 186 Participants |
| Previous Enrollment in SIMPLIFY-DA Study Yes | 45 Participants | 42 Participants | 87 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaskan Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other, More than one Race, or Unknown/Not Reported | 3 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Race White | 136 Participants | 128 Participants | 264 Participants |
| Sex: Female, Male Female | 63 Participants | 65 Participants | 128 Participants |
| Sex: Female, Male Male | 77 Participants | 68 Participants | 145 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 184 | 0 / 186 |
| other Total, other adverse events | 5 / 184 | 10 / 186 |
| serious Total, serious adverse events | 2 / 184 | 1 / 186 |
Outcome results
Primary
Absolute Change in FEV1 % Predicted From Week 0 to Week 6
Difference between study arms (discontinue - continue) in the absolute change in FEV1 % predicted from Week 0 to Week 6.
Time frame: Week 0 to Week 6
Population: Per Protocol Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HS-Discontinue | Absolute Change in FEV1 % Predicted From Week 0 to Week 6 | -0.2 FEV1 % predicted | Standard Deviation 4.1 |
| HS-Continue | Absolute Change in FEV1 % Predicted From Week 0 to Week 6 | 0.1 FEV1 % predicted | Standard Deviation 3.64 |
Comparison: The non-inferiority test was a priori designed to be conducted on the per-protocol (PP) population.p-value: <0.000195% CI: [-1.3, 0.6]ANOVA
Secondary
Absolute Change in FEV1 % Predicted From Week 0 to Week 2
Difference between study arms (discontinue - continue) in the absolute change in FEV1 % predicted from Week 0 to Week 2.
Time frame: Week 0 to Week 2
Population: Participants in the per-protocol (PP) population with FEV1 measurements at Week 0 and at Week 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HS-Discontinue | Absolute Change in FEV1 % Predicted From Week 0 to Week 2 | 0.3 % predicted | Standard Deviation 3.66 |
| HS-Continue | Absolute Change in FEV1 % Predicted From Week 0 to Week 2 | 0.6 % predicted | Standard Deviation 2.94 |
p-value: 0.5695% CI: [-1.04, 0.57]t-test, 2 sided
Secondary
Absolute Change in FEV1 % Predicted From Week -2 to Week 0
Difference between study arms (discontinue - continue) in the absolute change in FEV1 % predicted from Week -2 to Week 0.
Time frame: Week -2 to Week 0
Population: Per-protocol (PP) population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HS-Discontinue | Absolute Change in FEV1 % Predicted From Week -2 to Week 0 | 0.2 % predicted | Standard Deviation 3.63 |
| HS-Continue | Absolute Change in FEV1 % Predicted From Week -2 to Week 0 | -0.4 % predicted | Standard Deviation 3.86 |
p-value: 0.1695% CI: [-0.25, 1.54]t-test, 2 sided
Secondary
Absolute Change in LCI 2.5 From Baseline to Week 6
Difference between study arms (discontinue - continue) in the absolute change in LCI 2.5 (Lung Clearance Index) from Baseline (Week 0, if available, or else Week -2) to Week 6. LCI 2.5 is the number of times the volume in the lungs needs to turn over to expel an inert gas. A higher value of LCI 2.5 indicates poorer lung function.
Time frame: Baseline (Week 0 or Week -2) to Week 6
Population: Participants in the per-protocol (PP) population with an acceptable LCI 2.5 measurement at baseline and at Week 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HS-Discontinue | Absolute Change in LCI 2.5 From Baseline to Week 6 | 0.1 number of lung volume turnovers | Standard Deviation 0.72 |
| HS-Continue | Absolute Change in LCI 2.5 From Baseline to Week 6 | 0.1 number of lung volume turnovers | Standard Deviation 0.73 |
p-value: 0.73395% CI: [-0.4, 0.4]ANOVA
Secondary
Absolute Change in Respiratory Symptoms, as Measured by CFQ-R Respiratory Domain From Week 0 to Week 6
Difference between study arms (discontinue - continue) in the absolute change in respiratory symptoms, as measured by the Cystic Fibrosis Questionnaire-Revised Respiratory Domain Score from Week 0 to Week 6. The Cystic Fibrosis Questionnaire - Revised asks participants 6 questions related to respiratory symptoms which are each assigned a score 1-4. The Respiratory Domain Scaled Score is calculated as follows: 100\*\[{sum of responses}/{number of responses}-1\]/3 only if number of responses ≥ 3; otherwise the score is set to missing. The scaled score ranges from 0 to 100 where higher scores indicate improvement of symptoms.
Time frame: Week 0 to Week 6
Population: Participants in the per-protocol (PP) population with a score at Week 0 and at Week 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HS-Discontinue | Absolute Change in Respiratory Symptoms, as Measured by CFQ-R Respiratory Domain From Week 0 to Week 6 | 0.7 score on a scale | Standard Deviation 9.56 |
| HS-Continue | Absolute Change in Respiratory Symptoms, as Measured by CFQ-R Respiratory Domain From Week 0 to Week 6 | 0.5 score on a scale | Standard Deviation 6.35 |
p-value: 0.85795% CI: [-1.8, 2.1]ANOVA
Secondary
Absolute Change in Respiratory Symptoms, as Measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) From Week 0 to Week 6
Difference between study arms (discontinue - continue) in the absolute change in respiratory symptoms, as measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) from Week 0 to Week 6. The Cystic Fibrosis Respiratory Symptoms Daily Diary (CFRSD) asks a participant to state the extent of their 8 respiratory symptoms: difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the response, with zero corresponding to the absence of the symptom and four corresponding to symptom being present 'a great deal' or 'extremely'. A summed score (range from 0-24) is calculated for each participant and converted to a final score with a range of 0 to 100, where the lowest scores indicate improvement of symptoms. Calculation of a score requires responses for at least 7 out of 8 symptoms.
Time frame: Week 0 to Week 6
Population: Participants in the per-protocol (PP) population with a CRISS score at Week 0 and Week 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HS-Discontinue | Absolute Change in Respiratory Symptoms, as Measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) From Week 0 to Week 6 | -1.4 score on a scale | Standard Deviation 11.02 |
| HS-Continue | Absolute Change in Respiratory Symptoms, as Measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) From Week 0 to Week 6 | 0.2 score on a scale | Standard Deviation 9.73 |
p-value: 0.22695% CI: [-4.1, 0.9]ANOVA
Secondary
Number and Percent of Participants Experiencing Adverse Events (AEs) From Week 0 to Week 6
Difference between study arms (discontinue - continue) in the percent of participants with at least one AE from Week 0 to Week 6. Includes serious and non-serious AEs.
Time frame: Week 0 to Week 6
Population: Intent-to-treat (ITT) population of all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HS-Discontinue | Number and Percent of Participants Experiencing Adverse Events (AEs) From Week 0 to Week 6 | 65 Participants |
| HS-Continue | Number and Percent of Participants Experiencing Adverse Events (AEs) From Week 0 to Week 6 | 44 Participants |
Comparison: Null hypothesis: proportion of participants with at least one AE is the same in Discontinue and Continue arms.p-value: 0.016595% CI: [2.4, 20.7]Fisher Exact
Secondary
Number and Percent of Participants Experiencing Pulmonary Exacerbations From Week 0 to Week 6
Difference between study arms (discontinue - continue) in the percent of subjects experiencing a pulmonary exacerbation from Week 0 to Week 6. Pulmonary exacerbations defined using Fuchs criteria.
Time frame: Week 0 to Week 6
Population: Intent-to-treat (ITT) population of all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HS-Discontinue | Number and Percent of Participants Experiencing Pulmonary Exacerbations From Week 0 to Week 6 | 1 Participants |
| HS-Continue | Number and Percent of Participants Experiencing Pulmonary Exacerbations From Week 0 to Week 6 | 3 Participants |
Comparison: Null hypothesis: proportion of participants with at least one protocol-defined pulmonary exacerbation is the same in Discontinue and Continue arms.p-value: 0.62395% CI: [-4.1, 1.6]Fisher Exact
Secondary
Number and Percent of Participants Hospitalized From Week 0 to Week 6
Difference between study arms (discontinue - continue) in the percent of subjects hospitalized from Week 0 to Week 6.
Time frame: Week 0 to Week 6
Population: Intent-to-treat (ITT) population of all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HS-Discontinue | Number and Percent of Participants Hospitalized From Week 0 to Week 6 | 2 Participants |
| HS-Continue | Number and Percent of Participants Hospitalized From Week 0 to Week 6 | 1 Participants |
Comparison: Null hypothesis: proportion of participants with at least one hospitalization is the same in Discontinue and Continue arms.p-value: 0.62295% CI: [-2, 3.4]Fisher Exact
Secondary
Number and Percent of Participants Initiating Acute Antibiotics From Week 0 to Week 6
Difference between study arms (discontinue - continue) in the percent of subjects initiating acute oral, inhaled or intravenous antibiotics from Week 0 to Week 6. Includes antibiotics initiated for respiratory indications; excludes those taken as part of a chronic cycled regimen or for a UTI, skin infection, etc.
Time frame: Week 0 to Week 6
Population: Intent to treat (ITT) population of all randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HS-Discontinue | Number and Percent of Participants Initiating Acute Antibiotics From Week 0 to Week 6 | 11 Participants |
| HS-Continue | Number and Percent of Participants Initiating Acute Antibiotics From Week 0 to Week 6 | 9 Participants |
Comparison: Null hypothesis: proportion of participants initiating acute antibiotics is the same in the Discontinue and Continue armsp-value: 0.65395% CI: [-3.7, 6.1]Fisher Exact
Secondary
Number and Percent of Participants With Temporary or Permanent Changes From Assigned Therapy Regimen Due to Adverse Event From Week 0 to Week 6
Difference between study arms (discontinue - continue) in the percent of subjects temporarily or permanently changing their assigned therapy regimen due to an adverse event Week 0 to Week 6
Time frame: Week 0 to Week 6
Population: Intent-to-treat (ITT) population of all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HS-Discontinue | Number and Percent of Participants With Temporary or Permanent Changes From Assigned Therapy Regimen Due to Adverse Event From Week 0 to Week 6 | 5 Participants |
| HS-Continue | Number and Percent of Participants With Temporary or Permanent Changes From Assigned Therapy Regimen Due to Adverse Event From Week 0 to Week 6 | 1 Participants |
Comparison: Null hypothesis: proportion of participants changing assigned regimen is the same in Discontinue and Continue arms.p-value: 0.121595% CI: [-0.7, 5.7]Fisher Exact
Secondary
Rate of Adverse Events (AEs) From Week 0 to Week 6 Therapy Arms
Comparison of study arms (discontinue/continue) in the rate of AE occurrence (number of events divided by total follow-up weeks in each arm) from Week 0 to Week 6. Includes serious and non-serious AEs.
Time frame: Week 0 to Week 6
Population: Intent-to-treat (ITT) population of all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HS-Discontinue | Rate of Adverse Events (AEs) From Week 0 to Week 6 Therapy Arms | 0.086 events per week |
| HS-Continue | Rate of Adverse Events (AEs) From Week 0 to Week 6 Therapy Arms | 0.067 events per week |
Comparison: Rate ratio, confidence interval, and p-value calculated using Poisson Regression with an offset for the log of follow-up time in weeks. The total number of follow-up weeks in the HS-discontinue and HS-continue arms are 1135.7 and 1163.9 weeks, respectively. Ratio is Discontinue / Continue.p-value: 0.095895% CI: [0.96, 1.74]Poisson Regression