Cystic Fibrosis
Conditions
Keywords
Inflammation, Essential Fatty Acids, Inflammation resolution, Docosahexaenoic acid, Lung function
Brief summary
An International Phase II, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of LAU-7b administered once-daily for 6 months for the treatment of CF.
Detailed description
An International Phase II, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of LAU-7b administered once-daily for 6 months for the treatment of CF. All patients will remain on their CF standard-of-care treatments over the trial duration. The goal for the treatment with LAU-7b in CF is to preserve lung function by reducing the persistent inflammation in the lung and to improve its capacity to defend against resistant bacteria such as Pseudomonas aeruginosa. The treatment regimen will consist of 6 consecutive dosing cycles of 21 days each, spaced by study drug-free periods of 7 days. A total of 136 eligible adult patients with CF will be randomized to receive 300 mg LAU-7b or placebo in a 1:1 ratio. The participation in the study will last about 7 months.
Interventions
DRUGLAU-7b
LAU-7b will be administered orally once-a-day with the first meal of the day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
DRUGPlacebo oral capsule
Placebo will be administered orally once-a-day with the first meal of the day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
Sponsors
Cystic Fibrosis Foundation
Laurent Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Patients will be randomly assigned to take either the active drug (fenretinide capsule) or a matching inactive placebo (inactive capsule).
Intervention model description
Double-blind, randomized, parallel groups and placebo-controlled trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Screening FEV1 between 40% and 100% predicted value for age, gender and height, in patients capable of properly performing the test; * History of pulmonary exacerbation, defined as at least one (1) pulmonary exacerbation in the year prior to Screening which resulted in documented intravenous or Oral antibiotics; * Patients are eligible independently of their history of pulmonary Pseudomonas aeruginosa (PsA) infection and their PsA status at screening; * If taking Kalydeco® (ivacaftor), Orkambi® (ivacaftor/lumacaftor), Symdeko® (ivacaftor/tezacaftor) or other commercially available CFTR modulator products, patients must be taking it for a minimum of 3 months prior to screening if naïve to CFTR modulators and 1 month if switched from another CFTR modulator product and deemed to tolerate it; * No change in CF and allowed systemic chronic therapy for a minimum of 5 weeks prior to randomization, of which 2 weeks minimum are prior to screening; * Female patients of child bearing potential should be on highly effective contraceptive methods during the study; * Male patients with spouse or partner of child bearing potential, or pregnant, are eligible if they use an appropriate method of contraception.
Exclusion criteria
* Pregnancy: due to the potential teratogenic effects of retinoids, pregnant women are NOT eligible; * Breast milk feeding by study patient is NOT allowed; * Clinically abnormal renal function: serum creatinine \> 132 μM (1.5 mg/dL); * Clinically abnormal liver function: Total bilirubin \>1.5 x ULN (in the absence of demonstrated Gilbert's syndrome), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 2.5 x ULN; * Patients with plasma retinol levels below 0.7 µM; * Presence of nyctalopia or hemeralopia at enrolment, or any other serious retinal, ophthalmological condition; * Presence of serious dermatological conditions at entry, including inflammatory or xerotic skin pathologies such as psoriasis or ichthyosis; * Intake of chronic systemic steroids in the month prior to screening and during the study; * History of acute infections (viral/bacterial/fungal) within 5 weeks prior to randomization, of which 2 weeks minimum are prior to screening, whether or not treated and resolved; * Presence of infection with Burkholderia cepacia (including all species within the Burkholderia cepacia complex group, and Burkholderia gladioli) in the 12 months prior to screening; * Patients with a confirmed diagnosis (as per the Cystic Fibrosis Foundation diagnostic criteria) of Allergic BronchoPulmonary Aspergillosis (ABPA) and actively being treated with corticosteroids and/or anti fungal agents.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | From Baseline to 28 weeks | This was assessed through adverse event monitoring at all visits, including spontaneously reported events and those obtained through serial probing of the subjects, and from safety laboratory tests |
| Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%) | From baseline to 24 weeks | Standardized, serial FEV1 measurements were performed during the trial by the clinical sites using standardized spirometers. All spirometry measurements were centrally read and validated by the spirometry provider, Vitalograph. The outcome measure is presented using the Least Squares Mean at the Week 24 time point and the Least Squares Mean of all post-baseline time points through Week 24 averaged. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Patients Achieving Normalization of the Arachidonic Acid, Docosahexaenoic Acid and Their Ratio in Phospholipids | From baseline to 28 weeks | Assessed through 4 blood sampling occasions during the trial. Plasma samples were analyzed using a validated LC/MS method and corrected for phospholipid content. Highest proportion of normalization during treatment was determined versus analyte ranges obtained from a group of 20 healthy, non-CF individuals. |
| The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | From baseline to 3, 7, 11, 15, 24 and 28 weeks into the trial | Standardized, serial FEV1 measurements were performed during the trial by the clinical sites using standardized spirometers. All spirometry measurements were centrally read and validated by the spirometry provider, Vitalograph. |
| The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | From baseline to 3, 7, 11, 15, 24 and 28 weeks into the trial | Standardized, serial FEV1 measurements were performed during the trial by the clinical sites using standardized spirometers. All spirometry measurements were centrally read and validated by the spirometry provider, Vitalograph. |
| The Time to First Protocol-Defined Pulmonary Exacerbation | From baseline to 28 weeks | Reports of IV antibiotics-treated pulmonary exacerbations during the trial that meet the Fuch's criteria and after the first treatment cycle. |
| The Number Per Subject of Protocol-Defined Pulmonary Exacerbations (PEx) During the Trial | From baseline to 28 weeks | The number per subject of Protocol-Defined IV antibiotics-treated pulmonary exacerbations (events) during the trial that meet the Fuch's criteria. Also presented are the number per subject of IV antibiotics-treated pulmonary exacerbations and combined number per subject of IV- or Oral antibiotics-treated pulmonary exacerbations during the trial. Excluded are exacerbations occurring during the first treatment cycle. |
| The Time to First Change and Usage of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin) | From baseline to 28 weeks | The time to first change and usage of IV antibiotics to treat pulmonary exacerbations during the trial. Excluded are exacerbations occurring during the first treatment cycle. |
| The Change From Baseline of Systemic Markers of Inflammation in Blood | Change from baseline to Week 24 | This was assessed through scheduled blood sampling during the trial on three occasions. Both ITT and PP populations results presented. Samples were analyzed using validated analytical methods. |
| The Overall Change From Screening of the Pseudomonas Aeruginosa Density (Colony Forming Units) in the Sputum | From screening to Week 24 | This was assessed through induced sputum (and spontaneously obtained during COVID-19 pandemic) on 3 occasions during the trial. Samples were analyzed at a central laboratory. An area under the curve (AUC from baseline to Week 24 inclusive) of colony forming unit/mL is calculated. |
| The Impact (From Baseline) on Overall Health, Daily Life, Perceived Well-being and Symptoms Measured With the Cystic Fibrosis Questionnaire-Revised (CFQ-R) | From baseline to 24 weeks | This was assessed through administration of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at four planned times during the trial. The CFQ-R respiratory sub-score (range 0-100) was extracted and analyzed. The Minimum Clinically Important Difference (MCID) for the respiratory sub-score is 4 units. A higher score means a better outcome. |
| The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood | From baseline to 24 weeks | This was assessed through serial blood sampling during the trial. Samples were analyzed using validated methods at specialized laboratories. |
| Usage (Number of Antibiotic Treatments) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin) | From baseline to 28 weeks | Usage (number of antibiotic treatments per subject) of IV antibiotics to treat pulmonary exacerbations during the trial. Excluded are exacerbations occurring during the first treatment cycle. |
| Usage (Days) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin) | From baseline to 28 weeks | Usage (days) of IV antibiotics to treat pulmonary exacerbations during the trial. Excluded are exacerbations occurring during the first treatment cycle. |
| The Change From Screening of the Body Weight | From screening to 28 weeks | This was assessed through serial weighing during the trial. Measurements performed at clinical sites using calibrated balances. |
| The Change From Screening of the Body Mass Index (BMI) | From screening to 28 weeks | This was assessed through serial weighing during the trial and calculation of BMI. Measurements performed at clinical sites using calibrated balances. |
Other
| Measure | Time frame | Description |
|---|---|---|
| The Change in Metabolipidomic Profile in Blood, the Systemic Markers of Inflammation in Blood, the FEV1, the Body Weight and Calculated BMI | From baseline to 28 weeks | Only in patients who experience a pulmonary exacerbation requiring IV antibiotics, this was to be assessed prior to- and after receiving an IV antibiotic course. |
| The Change From Baseline of Systemic Bone Formation and Resorption Biomarkers | Baseline and 24 weeks | This was assessed through blood sampling on 2 occasions during the trial at Baseline and Week 24. |
| The Change From Baseline of Bone Mineral Density | Baseline and 28 weeks | This was assessed through Lumbar spine bone mineral density measured on 2 occasions during the trial at Baseline and at Week 28 in a subset of sites and on a voluntary basis. Bone mineral density in g/cm2 is then normalized and expressed as a Z-score distribution according to age and gender. A Z-score of 0 represents the population mean for the age and gender category, a -1 value or +1 value means below or above the population mean bone mineral density for the age and gender category, but considered normal. A -2.5 value indicates secondary osteoporosis, a worse outcome. |
Countries
Australia, Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LAU-7b Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b will be administered orally once-a-day with the first meal of the day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles. | 83 |
| Placebo Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo will be administered orally once-a-day with the first meal of the day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles. | 83 |
| Total | 166 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Any Other Reason | 7 | 3 |
| Overall Study | Drug Withdrawn | 3 | 3 |
| Overall Study | Withdrawal by Subject | 13 | 5 |
Baseline characteristics
| Characteristic | LAU-7b | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 31.5 years STANDARD_DEVIATION 10.7 | 33.9 years STANDARD_DEVIATION 12.95 | 32.7 years STANDARD_DEVIATION 11.9 |
| Age, Customized <=25 years | 29 Participants | 26 Participants | 55 Participants |
| Age, Customized >25 years | 54 Participants | 57 Participants | 111 Participants |
| BMI (kg/m2), Mean (SD) | 23.34 kg/m2 STANDARD_DEVIATION 3.354 | 23.39 kg/m2 STANDARD_DEVIATION 4.099 | 23.36 kg/m2 STANDARD_DEVIATION 3.734 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 2 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 76 Participants | 81 Participants | 157 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| FEV1 percent predicted at Baseline | 63.2 percent predicted STANDARD_DEVIATION 16.77 | 62.3 percent predicted STANDARD_DEVIATION 15.13 | 62.73 percent predicted STANDARD_DEVIATION 15.93 |
| Number of PEx in the previous year, (Mean (SD) | 2.3 Pulmonary Exacerbation STANDARD_DEVIATION 1.77 | 2.1 Pulmonary Exacerbation STANDARD_DEVIATION 1.54 | 2.2 Pulmonary Exacerbation STANDARD_DEVIATION 1.65 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 81 Participants | 78 Participants | 159 Participants |
| Region of Enrollment Australia | 11 participants | 10 participants | 21 participants |
| Region of Enrollment Canada | 24 participants | 22 participants | 46 participants |
| Region of Enrollment United States | 48 participants | 51 participants | 99 participants |
| Sex: Female, Male Female | 50 Participants | 49 Participants | 99 Participants |
| Sex: Female, Male Male | 33 Participants | 34 Participants | 67 Participants |
| Weight (kg), Mean (SD) | 63.88 kg STANDARD_DEVIATION 12.213 | 64.53 kg STANDARD_DEVIATION 14.329 | 64.20 kg STANDARD_DEVIATION 13.277 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 83 | 0 / 83 |
| other Total, other adverse events | 80 / 83 | 79 / 83 |
| serious Total, serious adverse events | 20 / 83 | 15 / 83 |
Outcome results
Primary
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%)
Standardized, serial FEV1 measurements were performed during the trial by the clinical sites using standardized spirometers. All spirometry measurements were centrally read and validated by the spirometry provider, Vitalograph. The outcome measure is presented using the Least Squares Mean at the Week 24 time point and the Least Squares Mean of all post-baseline time points through Week 24 averaged.
Time frame: From baseline to 24 weeks
Population: intent to treat population (ITT) and per-protocol population (PP)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| LAU-7b | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%) | ITT population at Week 24 | -1.1774 Change in FEV1 % predicted |
| LAU-7b | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%) | ITT population through Week 24 | -0.5417 Change in FEV1 % predicted |
| LAU-7b | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%) | PP population through Week 24 | -0.3374 Change in FEV1 % predicted |
| LAU-7b | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%) | ITT subgroup >=70% ppFEV1, at Week 24 | -1.4059 Change in FEV1 % predicted |
| LAU-7b | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%) | ITT subgroup on CFTR modulators, at Week 24 | -0.3336 Change in FEV1 % predicted |
| LAU-7b | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%) | ITT subgroup on ETI, at Week 24 | -0.7406 Change in FEV1 % predicted |
| Placebo | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%) | ITT subgroup on CFTR modulators, at Week 24 | -1.7247 Change in FEV1 % predicted |
| Placebo | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%) | ITT population at Week 24 | -1.9489 Change in FEV1 % predicted |
| Placebo | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%) | ITT subgroup >=70% ppFEV1, at Week 24 | -4.0687 Change in FEV1 % predicted |
| Placebo | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%) | ITT population through Week 24 | -1.5470 Change in FEV1 % predicted |
| Placebo | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%) | ITT subgroup on ETI, at Week 24 | -1.8709 Change in FEV1 % predicted |
| Placebo | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%) | PP population through Week 24 | -1.5632 Change in FEV1 % predicted |
Comparison: Primary analysis of the treatment effect at the Week 24 visit on the intent to treat population (ITT) Null hypothesis is no treatment differencep-value: 0.344995% CI: [-0.8397, 2.3828]Mixed Model for Repeated Measures
Comparison: Analysis of the overall treatment effect from baseline through Week 24 in the intent to treat population (ITT), Null hypothesis is no treatment differencep-value: 0.066795% CI: [-0.07, 2.0807]Mixed Model for Repeated Measures
Comparison: Secondary analysis of the overall treatment effect from baseline through Week 24 on the per protocol population (PP), null hypothesis is no treatment differencep-value: 0.048695% CI: [0.0078, 2.4438]Mixed Model for Repeated Measures
Comparison: Secondary analysis of treatment effect at the Week 24 visit for stratification factor ppFEV1 (\<70% or ≥70%) in intent to treat population (ITT), null hypothesis is no treatment difference.~Here presented is the analysis for subgroup ≥70%, n=29 (LAU-7b), n=27 (Placebo)p-value: 0.068795% CI: [-0.2069, 5.5325]Mixed Model for Repeated Measures
Comparison: Secondary analysis of treatment effect at the Week 24 visit for stratification factor co-administration of CFTR modulator (yes/no) in intent to treat population (ITT), null hypothesis is no treatment difference.~Here presented is the analysis for subgroup receiving CFTR modulators, n=41 (LAU-7b), n=46 (Placebo)p-value: 0.23695% CI: [-0.922, 3.7041]Mixed Model for Repeated Measures
Comparison: Secondary analysis of treatment effect at the Week 24 visit for à priori defined subgroup co-administration of ETI - elexacaftor/tezacaftor/ivacaftor (yes/no) in intent to treat population (ITT), null hypothesis is no treatment difference.~Here presented is the analysis for subgroup receiving ETI, n=18 (LAU-7b), n=23 (Placebo)p-value: 0.532395% CI: [-2.4447, 4.7052]Mixed Model for Repeated Measures
Primary
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
This was assessed through adverse event monitoring at all visits, including spontaneously reported events and those obtained through serial probing of the subjects, and from safety laboratory tests
Time frame: From Baseline to 28 weeks
Population: safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Infective pulmonary exacerbation of cystic fibrosis | 37 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Upper respiratory tract infections | 13 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Severe highest reported severity | 13 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Hemoptysis | 11 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Cough | 23 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Delayed light adaptation | 10 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Diarrhoea | 11 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Moderate highest reported severity | 45 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Fatigue | 10 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Delayed dark adaptation | 22 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Life threatening | 0 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Dyspnea | 10 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Night blindness | 15 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Glare | 9 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Mild highest reported severity | 22 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Visual impairment | 9 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Headache | 14 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Sputum increased | 7 Participants |
| LAU-7b | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Subjects with at least one TEAE with ≥10% incidence | 74 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Sputum increased | 13 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Subjects with at least one TEAE with ≥10% incidence | 64 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Mild highest reported severity | 27 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Moderate highest reported severity | 43 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Severe highest reported severity | 7 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Life threatening | 0 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Infective pulmonary exacerbation of cystic fibrosis | 32 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Cough | 24 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Delayed dark adaptation | 4 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Night blindness | 2 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Headache | 10 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Upper respiratory tract infections | 8 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Hemoptysis | 13 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Diarrhoea | 6 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Fatigue | 7 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Delayed light adaptation | 2 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Dyspnea | 11 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Glare | 6 Participants |
| Placebo | Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence | Visual impairment | 2 Participants |
Secondary
The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial
Standardized, serial FEV1 measurements were performed during the trial by the clinical sites using standardized spirometers. All spirometry measurements were centrally read and validated by the spirometry provider, Vitalograph.
Time frame: From baseline to 3, 7, 11, 15, 24 and 28 weeks into the trial
Population: Intent to treat population (ITT)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LAU-7b | The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Absolute change at Week 3 | -0.243 FEV1 percent predicted change | Standard Deviation 5.11 |
| LAU-7b | The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Absolute change at Week 7 | 0.280 FEV1 percent predicted change | Standard Deviation 4.689 |
| LAU-7b | The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Absolute change at Week 11 | -0.309 FEV1 percent predicted change | Standard Deviation 4.268 |
| LAU-7b | The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Absolute change at Week 15 | -0.508 FEV1 percent predicted change | Standard Deviation 5.1 |
| LAU-7b | The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Absolute change at Week 24 | -1.024 FEV1 percent predicted change | Standard Deviation 4.286 |
| LAU-7b | The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Absolute change at Week 28 | -1.539 FEV1 percent predicted change | Standard Deviation 4.808 |
| Placebo | The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Absolute change at Week 24 | -1.759 FEV1 percent predicted change | Standard Deviation 4.533 |
| Placebo | The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Absolute change at Week 3 | -1.494 FEV1 percent predicted change | Standard Deviation 4.537 |
| Placebo | The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Absolute change at Week 15 | -1.591 FEV1 percent predicted change | Standard Deviation 4.389 |
| Placebo | The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Absolute change at Week 7 | -0.888 FEV1 percent predicted change | Standard Deviation 3.968 |
| Placebo | The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Absolute change at Week 28 | -1.413 FEV1 percent predicted change | Standard Deviation 4.457 |
| Placebo | The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Absolute change at Week 11 | -0.871 FEV1 percent predicted change | Standard Deviation 4.133 |
Secondary
The Change From Baseline of Systemic Markers of Inflammation in Blood
This was assessed through scheduled blood sampling during the trial on three occasions. Both ITT and PP populations results presented. Samples were analyzed using validated analytical methods.
Time frame: Change from baseline to Week 24
Population: Intent to treat population (ITT) and per-protocol population (PP)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LAU-7b | The Change From Baseline of Systemic Markers of Inflammation in Blood | Absolute change from baseline of C-reactive protein at Week 24 ITT Population | -1.197 Change in mg/L | Standard Deviation 7.904 |
| LAU-7b | The Change From Baseline of Systemic Markers of Inflammation in Blood | Absolute change from baseline of calprotectin at Week 24, ITT population | -27 Change in mg/L | Standard Deviation 962 |
| LAU-7b | The Change From Baseline of Systemic Markers of Inflammation in Blood | Absolute change from baseline of C-reactive protein at Week 24 PP Population | -1.216 Change in mg/L | Standard Deviation 7.987 |
| LAU-7b | The Change From Baseline of Systemic Markers of Inflammation in Blood | Absolute change from baseline of calprotectin at Week 24, PP population | -18 Change in mg/L | Standard Deviation 970 |
| Placebo | The Change From Baseline of Systemic Markers of Inflammation in Blood | Absolute change from baseline of calprotectin at Week 24, PP population | 478 Change in mg/L | Standard Deviation 2088 |
| Placebo | The Change From Baseline of Systemic Markers of Inflammation in Blood | Absolute change from baseline of C-reactive protein at Week 24 ITT Population | 2.532 Change in mg/L | Standard Deviation 10.65 |
| Placebo | The Change From Baseline of Systemic Markers of Inflammation in Blood | Absolute change from baseline of C-reactive protein at Week 24 PP Population | 2.532 Change in mg/L | Standard Deviation 10.654 |
| Placebo | The Change From Baseline of Systemic Markers of Inflammation in Blood | Absolute change from baseline of calprotectin at Week 24, ITT population | 478 Change in mg/L | Standard Deviation 2088 |
Comparison: C-Reactive Protein (CRP), Intent-to-Treat population (ITT), null hypothesis is no treatment effectp-value: 0.082295% CI: [-6.154, 0.374]Mixed Model for Repeated Measures
Comparison: Calprotectin, Intent-to-Treat population (ITT), null hypothesis is no treatment effectp-value: 0.060395% CI: [-1177, 25.4]Mixed Model for Repeated Measures
Comparison: C-Reactive Protein (CRP), Per-Protocol population (PP), null hypothesis is no treatment effectp-value: 0.028795% CI: [-7.297, -0.408]Mixed Model for Repeated Measures
Comparison: Calprotectin, Per-Protocol population (PP), null hypothesis is no treatment effectp-value: 0.045995% CI: [-1228, 12]Mixed Model for Repeated Measures
Secondary
The Change From Screening of the Body Mass Index (BMI)
This was assessed through serial weighing during the trial and calculation of BMI. Measurements performed at clinical sites using calibrated balances.
Time frame: From screening to 28 weeks
Population: Intent to treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LAU-7b | The Change From Screening of the Body Mass Index (BMI) | -0.162 Change in kg/m2 | Standard Deviation 0.922 |
| Placebo | The Change From Screening of the Body Mass Index (BMI) | 0.037 Change in kg/m2 | Standard Deviation 0.706 |
Comparison: Body mass index, intent to treat population (ITT), null hypothesis is no treatment effectp-value: 0.124695% CI: [-0.312, 0.038]Mixed Model for Repeated Measures
Secondary
The Change From Screening of the Body Weight
This was assessed through serial weighing during the trial. Measurements performed at clinical sites using calibrated balances.
Time frame: From screening to 28 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LAU-7b | The Change From Screening of the Body Weight | -0.43 Change in kg | Standard Deviation 2.41 |
| Placebo | The Change From Screening of the Body Weight | 0.14 Change in kg | Standard Deviation 1.96 |
Comparison: Body weight, Intent to treat population (ITT), null hypothesis is no treatment effectp-value: 0.100695% CI: [-0.86, 0.08]Mixed Model for Repeated Measures
Secondary
The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood
This was assessed through serial blood sampling during the trial. Samples were analyzed using validated methods at specialized laboratories.
Time frame: From baseline to 24 weeks
Population: Absolute change from Baseline at Week 24. Intent to treat population (ITT) in subjects with samples analyzed at baseline and at Week 24
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LAU-7b | The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood | 12-Hydroxy Eicosatetraenoic Acid | -0.00445 umol/L | Standard Deviation 0.491341 |
| LAU-7b | The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood | 8-Hydroxy Eicosatetraenoic Acid | -0.00744 umol/L | Standard Deviation 0.093498 |
| LAU-7b | The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood | 15-Hydroxy Eicosapentaenoic Acid | 0.00069 umol/L | Standard Deviation 0.025828 |
| LAU-7b | The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood | Thiobarbituric Acid Reactive Substances | -0.0504 umol/L | Standard Deviation 0.7994 |
| LAU-7b | The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood | 11-Hydroxy Eicosatetraenoic Acid | -0.0195 umol/L | Standard Deviation 0.13559 |
| LAU-7b | The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood | Nitrotyrosine (NT3) | -1.57 umol/L | Standard Deviation 72.964 |
| LAU-7b | The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood | 19,20-diHydroxy Docosapentaenoic Acid | 0.16447 umol/L | Standard Deviation 0.865788 |
| Placebo | The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood | Nitrotyrosine (NT3) | 10.35 umol/L | Standard Deviation 146.824 |
| Placebo | The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood | 11-Hydroxy Eicosatetraenoic Acid | 0.0187 umol/L | Standard Deviation 0.08397 |
| Placebo | The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood | 15-Hydroxy Eicosapentaenoic Acid | 0.02028 umol/L | Standard Deviation 0.059147 |
| Placebo | The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood | 19,20-diHydroxy Docosapentaenoic Acid | 0.06606 umol/L | Standard Deviation 0.568695 |
| Placebo | The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood | 8-Hydroxy Eicosatetraenoic Acid | 0.01879 umol/L | Standard Deviation 0.088266 |
| Placebo | The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood | Thiobarbituric Acid Reactive Substances | 0.0406 umol/L | Standard Deviation 1.19656 |
| Placebo | The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood | 12-Hydroxy Eicosatetraenoic Acid | -0.01181 umol/L | Standard Deviation 0.820744 |
Secondary
The Impact (From Baseline) on Overall Health, Daily Life, Perceived Well-being and Symptoms Measured With the Cystic Fibrosis Questionnaire-Revised (CFQ-R)
This was assessed through administration of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at four planned times during the trial. The CFQ-R respiratory sub-score (range 0-100) was extracted and analyzed. The Minimum Clinically Important Difference (MCID) for the respiratory sub-score is 4 units. A higher score means a better outcome.
Time frame: From baseline to 24 weeks
Population: Absolute change of CFQ-R Respiratory sub-score, from Baseline to Week 24. Intent to treat population (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LAU-7b | The Impact (From Baseline) on Overall Health, Daily Life, Perceived Well-being and Symptoms Measured With the Cystic Fibrosis Questionnaire-Revised (CFQ-R) | -2.485 Change of units on a scale | Standard Deviation 20.28 |
| Placebo | The Impact (From Baseline) on Overall Health, Daily Life, Perceived Well-being and Symptoms Measured With the Cystic Fibrosis Questionnaire-Revised (CFQ-R) | 0.235 Change of units on a scale | Standard Deviation 11.44 |
Comparison: CFQ-R Respiratory subscore, intent to treat population (ITT), null hypothesis is no treatment effectp-value: 0.299695% CI: [-7.998, 2.482]Mixed Model for Repeated Measures
Secondary
The Number Per Subject of Protocol-Defined Pulmonary Exacerbations (PEx) During the Trial
The number per subject of Protocol-Defined IV antibiotics-treated pulmonary exacerbations (events) during the trial that meet the Fuch's criteria. Also presented are the number per subject of IV antibiotics-treated pulmonary exacerbations and combined number per subject of IV- or Oral antibiotics-treated pulmonary exacerbations during the trial. Excluded are exacerbations occurring during the first treatment cycle.
Time frame: From baseline to 28 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LAU-7b | The Number Per Subject of Protocol-Defined Pulmonary Exacerbations (PEx) During the Trial | Protocol-Defined IV-treated PEx events per subject | 0.16 Events per subject | Standard Deviation 0.398 |
| LAU-7b | The Number Per Subject of Protocol-Defined Pulmonary Exacerbations (PEx) During the Trial | All IV-treated PEx events per subject | 0.24 Events per subject | Standard Deviation 0.458 |
| LAU-7b | The Number Per Subject of Protocol-Defined Pulmonary Exacerbations (PEx) During the Trial | All IV- or Oral antibiotics-treated PEx events per subject | 0.53 Events per subject | Standard Deviation 0.721 |
| Placebo | The Number Per Subject of Protocol-Defined Pulmonary Exacerbations (PEx) During the Trial | Protocol-Defined IV-treated PEx events per subject | 0.10 Events per subject | Standard Deviation 0.335 |
| Placebo | The Number Per Subject of Protocol-Defined Pulmonary Exacerbations (PEx) During the Trial | All IV-treated PEx events per subject | 0.18 Events per subject | Standard Deviation 0.566 |
| Placebo | The Number Per Subject of Protocol-Defined Pulmonary Exacerbations (PEx) During the Trial | All IV- or Oral antibiotics-treated PEx events per subject | 0.47 Events per subject | Standard Deviation 0.817 |
Comparison: Protocol-Defined IV antibiotics-treated pulmonary exacerbation events. Intent to treat population (ITT), null hypothesis is no treatment effectp-value: 0.336695% CI: [0.63, 3.8]Regression, Cox
Comparison: ALL IV antibiotics-treated pulmonary exacerbation events. Intent to treat population (ITT), null hypothesis is no treatment effectp-value: 0.393695% CI: [0.68, 2.64]Regression, Cox
Comparison: Combined IV- or Oral antibiotics-treated pulmonary exacerbation events. Intent to treat population (ITT), null hypothesis is no treatment effectp-value: 0.501195% CI: [0.75, 1.79]Regression, Cox
Secondary
The Overall Change From Screening of the Pseudomonas Aeruginosa Density (Colony Forming Units) in the Sputum
This was assessed through induced sputum (and spontaneously obtained during COVID-19 pandemic) on 3 occasions during the trial. Samples were analyzed at a central laboratory. An area under the curve (AUC from baseline to Week 24 inclusive) of colony forming unit/mL is calculated.
Time frame: From screening to Week 24
Population: Intent to treat population (ITT) with samples at screening and post-screening timepoints, and at sites able to obtain sputum samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LAU-7b | The Overall Change From Screening of the Pseudomonas Aeruginosa Density (Colony Forming Units) in the Sputum | 17681448107 CFU*weeks/mL | Standard Deviation 33050105775 |
| Placebo | The Overall Change From Screening of the Pseudomonas Aeruginosa Density (Colony Forming Units) in the Sputum | 10218800226 CFU*weeks/mL | Standard Deviation 16808101968 |
Comparison: Intent to treat population (ITT), null hypothesis is no treatment effectp-value: 0.764ANOVA
Secondary
The Proportion of Patients Achieving Normalization of the Arachidonic Acid, Docosahexaenoic Acid and Their Ratio in Phospholipids
Assessed through 4 blood sampling occasions during the trial. Plasma samples were analyzed using a validated LC/MS method and corrected for phospholipid content. Highest proportion of normalization during treatment was determined versus analyte ranges obtained from a group of 20 healthy, non-CF individuals.
Time frame: From baseline to 28 weeks
Population: Intent to treat population with analytical results at any sampling visit up to 28 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LAU-7b | The Proportion of Patients Achieving Normalization of the Arachidonic Acid, Docosahexaenoic Acid and Their Ratio in Phospholipids | Arachidonic acid (AA) normalization | 15 Participants |
| LAU-7b | The Proportion of Patients Achieving Normalization of the Arachidonic Acid, Docosahexaenoic Acid and Their Ratio in Phospholipids | Docosahexaenoic acid (DHA) normalization | 16 Participants |
| LAU-7b | The Proportion of Patients Achieving Normalization of the Arachidonic Acid, Docosahexaenoic Acid and Their Ratio in Phospholipids | AA/DHA ratio normalization | 25 Participants |
| Placebo | The Proportion of Patients Achieving Normalization of the Arachidonic Acid, Docosahexaenoic Acid and Their Ratio in Phospholipids | Arachidonic acid (AA) normalization | 25 Participants |
| Placebo | The Proportion of Patients Achieving Normalization of the Arachidonic Acid, Docosahexaenoic Acid and Their Ratio in Phospholipids | Docosahexaenoic acid (DHA) normalization | 18 Participants |
| Placebo | The Proportion of Patients Achieving Normalization of the Arachidonic Acid, Docosahexaenoic Acid and Their Ratio in Phospholipids | AA/DHA ratio normalization | 23 Participants |
Comparison: Highest normalization of Arachidonic Acid (AA) during treatment Intent to treat population (ITT), null hypothesis is no treatment effectp-value: 0.104795% CI: [0.2199, 1.1532]Regression, Logistic
Comparison: Highest normalization of Docosahexaenoic Acid (DHA) during treatment Intent to treat population (ITT, null hypothesis is no treatment effectp-value: 0.759695% CI: [0.3793, 2.0291]Regression, Logistic
Comparison: Highest normalization of AA/DHA ratio during treatment Intent to treat population (ITT), null hypothesis is no treatment effectp-value: 0.885295% CI: [0.5209, 2.1296]Regression, Logistic
Secondary
The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial
Standardized, serial FEV1 measurements were performed during the trial by the clinical sites using standardized spirometers. All spirometry measurements were centrally read and validated by the spirometry provider, Vitalograph.
Time frame: From baseline to 3, 7, 11, 15, 24 and 28 weeks into the trial
Population: Intent to treat population (ITT)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LAU-7b | The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Relative (%) change at Week 3 | -1.188 FEV1 percent predicted change | Standard Deviation 8.632 |
| LAU-7b | The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Relative (%) change at Week 7 | 0.561 FEV1 percent predicted change | Standard Deviation 8.348 |
| LAU-7b | The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Relative (%) change at Week 11 | -0.213 FEV1 percent predicted change | Standard Deviation 7.124 |
| LAU-7b | The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Relative (%) change at Week 15 | -0.924 FEV1 percent predicted change | Standard Deviation 8.963 |
| LAU-7b | The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Relative (%) change at Week 24 | -1.450 FEV1 percent predicted change | Standard Deviation 6.966 |
| LAU-7b | The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Relative (%) change at Week 28 | -2.388 FEV1 percent predicted change | Standard Deviation 8.275 |
| Placebo | The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Relative (%) change at Week 24 | -2.652 FEV1 percent predicted change | Standard Deviation 7.742 |
| Placebo | The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Relative (%) change at Week 3 | -2.341 FEV1 percent predicted change | Standard Deviation 7.289 |
| Placebo | The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Relative (%) change at Week 15 | -2.745 FEV1 percent predicted change | Standard Deviation 7.425 |
| Placebo | The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Relative (%) change at Week 7 | -1.550 FEV1 percent predicted change | Standard Deviation 6.829 |
| Placebo | The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Relative (%) change at Week 28 | -2.085 FEV1 percent predicted change | Standard Deviation 7.525 |
| Placebo | The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial | Relative (%) change at Week 11 | -1.277 FEV1 percent predicted change | Standard Deviation 7.12 |
Secondary
The Time to First Change and Usage of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)
The time to first change and usage of IV antibiotics to treat pulmonary exacerbations during the trial. Excluded are exacerbations occurring during the first treatment cycle.
Time frame: From baseline to 28 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LAU-7b | The Time to First Change and Usage of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin) | NA days |
| Placebo | The Time to First Change and Usage of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin) | NA days |
p-value: 0.1955Log Rank
Secondary
The Time to First Protocol-Defined Pulmonary Exacerbation
Reports of IV antibiotics-treated pulmonary exacerbations during the trial that meet the Fuch's criteria and after the first treatment cycle.
Time frame: From baseline to 28 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LAU-7b | The Time to First Protocol-Defined Pulmonary Exacerbation | NA days |
| Placebo | The Time to First Protocol-Defined Pulmonary Exacerbation | NA days |
p-value: 0.3025Log Rank
Secondary
Usage (Days) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)
Usage (days) of IV antibiotics to treat pulmonary exacerbations during the trial. Excluded are exacerbations occurring during the first treatment cycle.
Time frame: From baseline to 28 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LAU-7b | Usage (Days) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin) | 3.8 Days of IV antibiotics | Standard Deviation 7.5 |
| Placebo | Usage (Days) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin) | 3.5 Days of IV antibiotics | Standard Deviation 14.94 |
Comparison: Number of days of intravenous antibiotics required for a pulmonary exacerbation, excludes Cycle 1 pulmonary exacerbations, Intent to treat population (ITT), null hypothesis is no treatment effectp-value: 0.747395% CI: [0.6, 2.04]Poisson regression
Secondary
Usage (Number of Antibiotic Treatments) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)
Usage (number of antibiotic treatments per subject) of IV antibiotics to treat pulmonary exacerbations during the trial. Excluded are exacerbations occurring during the first treatment cycle.
Time frame: From baseline to 28 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LAU-7b | Usage (Number of Antibiotic Treatments) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin) | 0.53 Number of IV antibiotic treatments | Standard Deviation 1.09 |
| Placebo | Usage (Number of Antibiotic Treatments) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin) | 0.41 Number of IV antibiotic treatments | Standard Deviation 1.32 |
Comparison: Number per subject of intravenous antibiotic treatments required for a pulmonary exacerbation, excludes Cycle 1 pulmonary exacerbations Intent to treat population (ITT), null hypothesis is no treatment effectp-value: 0.190995% CI: [0.86, 2.12]Poisson regression
Other Pre-specified
The Change From Baseline of Bone Mineral Density
This was assessed through Lumbar spine bone mineral density measured on 2 occasions during the trial at Baseline and at Week 28 in a subset of sites and on a voluntary basis. Bone mineral density in g/cm2 is then normalized and expressed as a Z-score distribution according to age and gender. A Z-score of 0 represents the population mean for the age and gender category, a -1 value or +1 value means below or above the population mean bone mineral density for the age and gender category, but considered normal. A -2.5 value indicates secondary osteoporosis, a worse outcome.
Time frame: Baseline and 28 weeks
Population: Absolute change from Baseline at Week 24. Intent to treat population (ITT) in subjects volunteering to undergo bone density measurement
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LAU-7b | The Change From Baseline of Bone Mineral Density | -0.18 Z-score | Standard Deviation 0.69 |
| Placebo | The Change From Baseline of Bone Mineral Density | 0.09 Z-score | Standard Deviation 0.28 |
Other Pre-specified
The Change From Baseline of Systemic Bone Formation and Resorption Biomarkers
This was assessed through blood sampling on 2 occasions during the trial at Baseline and Week 24.
Time frame: Baseline and 24 weeks
Population: Absolute change from Baseline at Week 24. Intent to treat population (ITT)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LAU-7b | The Change From Baseline of Systemic Bone Formation and Resorption Biomarkers | Aminoterminal Propeptide | -5.0 Change in ug/L | Standard Deviation 14.9 |
| LAU-7b | The Change From Baseline of Systemic Bone Formation and Resorption Biomarkers | C-Telopeptide | -0.012 Change in ug/L | Standard Deviation 0.2092 |
| LAU-7b | The Change From Baseline of Systemic Bone Formation and Resorption Biomarkers | Osteocalcin | -1.46 Change in ug/L | Standard Deviation 6.181 |
| Placebo | The Change From Baseline of Systemic Bone Formation and Resorption Biomarkers | Aminoterminal Propeptide | -4.5 Change in ug/L | Standard Deviation 16.97 |
| Placebo | The Change From Baseline of Systemic Bone Formation and Resorption Biomarkers | C-Telopeptide | 0.015 Change in ug/L | Standard Deviation 0.1857 |
| Placebo | The Change From Baseline of Systemic Bone Formation and Resorption Biomarkers | Osteocalcin | 0.57 Change in ug/L | Standard Deviation 5.703 |
Other Pre-specified
The Change in Metabolipidomic Profile in Blood, the Systemic Markers of Inflammation in Blood, the FEV1, the Body Weight and Calculated BMI
Only in patients who experience a pulmonary exacerbation requiring IV antibiotics, this was to be assessed prior to- and after receiving an IV antibiotic course.
Time frame: From baseline to 28 weeks
Population: Only very few subjects got sampled pre- and post-pulmonary exacerbation, rendering this data anecdotic. No outcome measure is presented.