Trial Outcomes & Findings for Study of LAU-7b in the Treatment of Cystic Fibrosis in Adults (NCT NCT03265288)
NCT ID: NCT03265288
Last Updated: 2024-10-09
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
166 participants
Primary outcome timeframe
From baseline to 24 weeks
Results posted on
2024-10-09
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
83
|
83
|
|
Overall Study
COMPLETED
|
60
|
71
|
|
Overall Study
NOT COMPLETED
|
23
|
12
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
13
|
5
|
|
Overall Study
Drug Withdrawn
|
3
|
3
|
|
Overall Study
Any Other Reason
|
7
|
3
|
Baseline Characteristics
Study of LAU-7b in the Treatment of Cystic Fibrosis in Adults
Baseline characteristics by cohort
| Measure |
LAU-7b
n=83 Participants
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.
|
Placebo
n=83 Participants
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.
|
Total
n=166 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
31.5 years
STANDARD_DEVIATION 10.70 • n=5 Participants
|
33.9 years
STANDARD_DEVIATION 12.95 • n=7 Participants
|
32.7 years
STANDARD_DEVIATION 11.90 • n=5 Participants
|
|
Age, Customized
<=25 years
|
29 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
|
Age, Customized
>25 years
|
54 Participants
n=5 Participants
|
57 Participants
n=7 Participants
|
111 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
50 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
99 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
67 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
76 Participants
n=5 Participants
|
81 Participants
n=7 Participants
|
157 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
81 Participants
n=5 Participants
|
78 Participants
n=7 Participants
|
159 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
24 participants
n=5 Participants
|
22 participants
n=7 Participants
|
46 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
48 participants
n=5 Participants
|
51 participants
n=7 Participants
|
99 participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
11 participants
n=5 Participants
|
10 participants
n=7 Participants
|
21 participants
n=5 Participants
|
|
Weight (kg), Mean (SD)
|
63.88 kg
STANDARD_DEVIATION 12.213 • n=5 Participants
|
64.53 kg
STANDARD_DEVIATION 14.329 • n=7 Participants
|
64.20 kg
STANDARD_DEVIATION 13.277 • n=5 Participants
|
|
BMI (kg/m2), Mean (SD)
|
23.34 kg/m2
STANDARD_DEVIATION 3.354 • n=5 Participants
|
23.39 kg/m2
STANDARD_DEVIATION 4.099 • n=7 Participants
|
23.36 kg/m2
STANDARD_DEVIATION 3.734 • n=5 Participants
|
|
Number of PEx in the previous year, (Mean (SD)
|
2.3 Pulmonary Exacerbation
STANDARD_DEVIATION 1.77 • n=5 Participants
|
2.1 Pulmonary Exacerbation
STANDARD_DEVIATION 1.54 • n=7 Participants
|
2.2 Pulmonary Exacerbation
STANDARD_DEVIATION 1.65 • n=5 Participants
|
|
FEV1 percent predicted at Baseline
|
63.2 percent predicted
STANDARD_DEVIATION 16.77 • n=5 Participants
|
62.3 percent predicted
STANDARD_DEVIATION 15.13 • n=7 Participants
|
62.73 percent predicted
STANDARD_DEVIATION 15.93 • n=5 Participants
|
PRIMARY outcome
Timeframe: From baseline to 24 weeksPopulation: intent to treat population (ITT) and per-protocol population (PP)
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.
Outcome measures
| Measure |
LAU-7b
n=83 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=83 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%)
PP population through Week 24
|
-0.3374 Change in FEV1 % predicted
Interval -1.4987 to 0.8239
|
-1.5632 Change in FEV1 % predicted
Interval -2.7333 to -0.393
|
|
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%)
ITT population at Week 24
|
-1.1774 Change in FEV1 % predicted
Interval -2.5038 to 0.149
|
-1.9489 Change in FEV1 % predicted
Interval -3.2241 to -0.6738
|
|
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%)
ITT population through Week 24
|
-0.5417 Change in FEV1 % predicted
Interval -1.5226 to 0.4392
|
-1.5470 Change in FEV1 % predicted
Interval -2.5304 to -0.5637
|
|
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
Interval -3.5506 to 0.7388
|
-4.0687 Change in FEV1 % predicted
Interval -6.1289 to -2.0085
|
|
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
Interval -2.2467 to 1.5795
|
-1.7247 Change in FEV1 % predicted
Interval -3.2954 to -0.1539
|
|
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
Interval -3.7472 to 2.2659
|
-1.8709 Change in FEV1 % predicted
Interval -4.1669 to 0.4252
|
PRIMARY outcome
Timeframe: From Baseline to 28 weeksPopulation: safety population
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
Outcome measures
| Measure |
LAU-7b
n=83 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=83 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Subjects with at least one TEAE with ≥10% incidence
|
74 Participants
|
64 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Mild highest reported severity
|
22 Participants
|
27 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Moderate highest reported severity
|
45 Participants
|
43 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Severe highest reported severity
|
13 Participants
|
7 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Life threatening
|
0 Participants
|
0 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Infective pulmonary exacerbation of cystic fibrosis
|
37 Participants
|
32 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Cough
|
23 Participants
|
24 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Delayed dark adaptation
|
22 Participants
|
4 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Night blindness
|
15 Participants
|
2 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Headache
|
14 Participants
|
10 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Upper respiratory tract infections
|
13 Participants
|
8 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Hemoptysis
|
11 Participants
|
13 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Diarrhoea
|
11 Participants
|
6 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Fatigue
|
10 Participants
|
7 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Delayed light adaptation
|
10 Participants
|
2 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Dyspnea
|
10 Participants
|
11 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Glare
|
9 Participants
|
6 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Visual impairment
|
9 Participants
|
2 Participants
|
|
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
Sputum increased
|
7 Participants
|
13 Participants
|
SECONDARY outcome
Timeframe: From baseline to 28 weeksPopulation: Intent to treat population with analytical results at any sampling visit up 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.
Outcome measures
| Measure |
LAU-7b
n=58 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=61 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
The Proportion of Patients Achieving Normalization of the Arachidonic Acid, Docosahexaenoic Acid and Their Ratio in Phospholipids
Arachidonic acid (AA) normalization
|
15 Participants
|
25 Participants
|
|
The Proportion of Patients Achieving Normalization of the Arachidonic Acid, Docosahexaenoic Acid and Their Ratio in Phospholipids
Docosahexaenoic acid (DHA) normalization
|
16 Participants
|
18 Participants
|
|
The Proportion of Patients Achieving Normalization of the Arachidonic Acid, Docosahexaenoic Acid and Their Ratio in Phospholipids
AA/DHA ratio normalization
|
25 Participants
|
23 Participants
|
SECONDARY outcome
Timeframe: From baseline to 3, 7, 11, 15, 24 and 28 weeks into the trialPopulation: Intent to treat population (ITT)
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.
Outcome measures
| Measure |
LAU-7b
n=83 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=83 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
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
|
-0.888 FEV1 percent predicted change
Standard Deviation 3.968
|
|
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
|
-0.871 FEV1 percent predicted change
Standard Deviation 4.133
|
|
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 5.110
|
-1.494 FEV1 percent predicted change
Standard Deviation 4.537
|
|
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 5.100
|
-1.591 FEV1 percent predicted change
Standard Deviation 4.389
|
|
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
|
-1.759 FEV1 percent predicted change
Standard Deviation 4.533
|
|
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
|
-1.413 FEV1 percent predicted change
Standard Deviation 4.457
|
SECONDARY outcome
Timeframe: From baseline to 3, 7, 11, 15, 24 and 28 weeks into the trialPopulation: Intent to treat population (ITT)
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.
Outcome measures
| Measure |
LAU-7b
n=83 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=83 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
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
|
-2.085 FEV1 percent predicted change
Standard Deviation 7.525
|
|
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
|
-2.341 FEV1 percent predicted change
Standard Deviation 7.289
|
|
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
|
-1.550 FEV1 percent predicted change
Standard Deviation 6.829
|
|
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
|
-1.277 FEV1 percent predicted change
Standard Deviation 7.120
|
|
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
|
-2.745 FEV1 percent predicted change
Standard Deviation 7.425
|
|
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
|
-2.652 FEV1 percent predicted change
Standard Deviation 7.742
|
SECONDARY outcome
Timeframe: From baseline to 28 weeksReports of IV antibiotics-treated pulmonary exacerbations during the trial that meet the Fuch's criteria and after the first treatment cycle.
Outcome measures
| Measure |
LAU-7b
n=83 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=83 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
The Time to First Protocol-Defined Pulmonary Exacerbation
|
NA days
Insufficient number of participants with events
|
NA days
Insufficient number of participants with events
|
SECONDARY outcome
Timeframe: From baseline to 28 weeksThe 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.
Outcome measures
| Measure |
LAU-7b
n=83 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=83 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
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
|
0.10 Events per subject
Standard Deviation 0.335
|
|
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
|
0.18 Events per subject
Standard Deviation 0.566
|
|
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
|
0.47 Events per subject
Standard Deviation 0.817
|
SECONDARY outcome
Timeframe: From baseline to 28 weeksThe 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.
Outcome measures
| Measure |
LAU-7b
n=83 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=83 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
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
Insufficient number of participants with events
|
NA days
Insufficient number of participants with events
|
SECONDARY outcome
Timeframe: From baseline to 28 weeksUsage (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.
Outcome measures
| Measure |
LAU-7b
n=83 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=83 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
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
|
0.41 Number of IV antibiotic treatments
Standard Deviation 1.32
|
SECONDARY outcome
Timeframe: From baseline to 28 weeksUsage (days) of IV antibiotics to treat pulmonary exacerbations during the trial. Excluded are exacerbations occurring during the first treatment cycle.
Outcome measures
| Measure |
LAU-7b
n=83 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=83 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
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 7.50
|
3.5 Days of IV antibiotics
Standard Deviation 14.94
|
SECONDARY outcome
Timeframe: Change from baseline to Week 24Population: Intent to treat population (ITT) and per-protocol population (PP)
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.
Outcome measures
| Measure |
LAU-7b
n=83 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=83 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
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
|
478 Change in mg/L
Standard Deviation 2088
|
|
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
|
2.532 Change in mg/L
Standard Deviation 10.650
|
|
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
|
2.532 Change in mg/L
Standard Deviation 10.654
|
|
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
|
478 Change in mg/L
Standard Deviation 2088
|
SECONDARY outcome
Timeframe: From screening to 28 weeksThis was assessed through serial weighing during the trial. Measurements performed at clinical sites using calibrated balances.
Outcome measures
| Measure |
LAU-7b
n=83 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=83 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
The Change From Screening of the Body Weight
|
-0.43 Change in kg
Standard Deviation 2.41
|
0.14 Change in kg
Standard Deviation 1.96
|
SECONDARY outcome
Timeframe: From screening to 28 weeksPopulation: Intent to treat (ITT)
This was assessed through serial weighing during the trial and calculation of BMI. Measurements performed at clinical sites using calibrated balances.
Outcome measures
| Measure |
LAU-7b
n=83 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=83 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
The Change From Screening of the Body Mass Index (BMI)
|
-0.162 Change in kg/m2
Standard Deviation 0.922
|
0.037 Change in kg/m2
Standard Deviation 0.706
|
SECONDARY outcome
Timeframe: From screening to Week 24Population: Intent to treat population (ITT) with samples at screening and post-screening timepoints, and at sites able to obtain sputum samples
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.
Outcome measures
| Measure |
LAU-7b
n=26 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=31 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
The Overall Change From Screening of the Pseudomonas Aeruginosa Density (Colony Forming Units) in the Sputum
|
17681448107 CFU*weeks/mL
Standard Deviation 33050105775
|
10218800226 CFU*weeks/mL
Standard Deviation 16808101968
|
SECONDARY outcome
Timeframe: From baseline to 24 weeksPopulation: Absolute change of CFQ-R Respiratory sub-score, from Baseline to Week 24. Intent to treat population (ITT)
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.
Outcome measures
| Measure |
LAU-7b
n=83 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=83 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
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
|
0.235 Change of units on a scale
Standard Deviation 11.44
|
SECONDARY outcome
Timeframe: From baseline to 24 weeksPopulation: Absolute change from Baseline at Week 24. Intent to treat population (ITT) in subjects with samples analyzed at baseline and at Week 24
This was assessed through serial blood sampling during the trial. Samples were analyzed using validated methods at specialized laboratories.
Outcome measures
| Measure |
LAU-7b
n=83 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=83 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
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
|
0.0187 umol/L
Standard Deviation 0.08397
|
|
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
|
-0.01181 umol/L
Standard Deviation 0.820744
|
|
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
|
0.02028 umol/L
Standard Deviation 0.059147
|
|
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
|
0.06606 umol/L
Standard Deviation 0.568695
|
|
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
|
0.01879 umol/L
Standard Deviation 0.088266
|
|
The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood
Thiobarbituric Acid Reactive Substances
|
-0.0504 umol/L
Standard Deviation 0.79940
|
0.0406 umol/L
Standard Deviation 1.19656
|
|
The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood
Nitrotyrosine (NT3)
|
-1.57 umol/L
Standard Deviation 72.964
|
10.35 umol/L
Standard Deviation 146.824
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to 28 weeksPopulation: Only very few subjects got sampled pre- and post-pulmonary exacerbation, rendering this data anecdotic. No outcome measure is presented.
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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and 24 weeksPopulation: Absolute change from Baseline at Week 24. Intent to treat population (ITT)
This was assessed through blood sampling on 2 occasions during the trial at Baseline and Week 24.
Outcome measures
| Measure |
LAU-7b
n=83 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=83 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
The Change From Baseline of Systemic Bone Formation and Resorption Biomarkers
Aminoterminal Propeptide
|
-5.0 Change in ug/L
Standard Deviation 14.90
|
-4.5 Change in ug/L
Standard Deviation 16.97
|
|
The Change From Baseline of Systemic Bone Formation and Resorption Biomarkers
C-Telopeptide
|
-0.012 Change in ug/L
Standard Deviation 0.2092
|
0.015 Change in ug/L
Standard Deviation 0.1857
|
|
The Change From Baseline of Systemic Bone Formation and Resorption Biomarkers
Osteocalcin
|
-1.46 Change in ug/L
Standard Deviation 6.181
|
0.57 Change in ug/L
Standard Deviation 5.703
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and 28 weeksPopulation: Absolute change from Baseline at Week 24. Intent to treat population (ITT) in subjects volunteering to undergo bone density measurement
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.
Outcome measures
| Measure |
LAU-7b
n=6 Participants
Active drug fenretinide (as LAU-7b capsules)
LAU-7b: LAU-7b administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
Placebo
n=11 Participants
Placebo oral capsule (as inactive capsules identical to active arm)
Placebo oral capsule: Placebo administered orally once-a-day as cycles of 21 days on, 7 days off, for a total of 6 planned cycles.
|
|---|---|---|
|
The Change From Baseline of Bone Mineral Density
|
-0.18 Z-score
Standard Deviation 0.69
|
0.09 Z-score
Standard Deviation 0.28
|
Adverse Events
LAU-7b
Serious events: 20 serious events
Other events: 80 other events
Deaths: 0 deaths
Placebo
Serious events: 15 serious events
Other events: 79 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LAU-7b
n=83 participants at risk
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.
|
Placebo
n=83 participants at risk
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.
|
|---|---|---|
|
Eye disorders
Loss of visual contrast sensitivity
|
1.2%
1/83 • 28 weeks
|
0.00%
0/83 • 28 weeks
|
|
Gastrointestinal disorders
Distal intestinal obstruction syndrome
|
2.4%
2/83 • 28 weeks
|
2.4%
2/83 • 28 weeks
|
|
Gastrointestinal disorders
Constipation
|
1.2%
1/83 • 28 weeks
|
0.00%
0/83 • 28 weeks
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/83 • 28 weeks
|
1.2%
1/83 • 28 weeks
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
18.1%
15/83 • 28 weeks
|
12.0%
10/83 • 28 weeks
|
|
Infections and infestations
Appendicitis
|
2.4%
2/83 • 28 weeks
|
0.00%
0/83 • 28 weeks
|
|
Infections and infestations
Influenza
|
1.2%
1/83 • 28 weeks
|
0.00%
0/83 • 28 weeks
|
|
Infections and infestations
Pneumonia staphylococcal
|
1.2%
1/83 • 28 weeks
|
0.00%
0/83 • 28 weeks
|
|
Infections and infestations
Pneumonia
|
0.00%
0/83 • 28 weeks
|
1.2%
1/83 • 28 weeks
|
|
Injury, poisoning and procedural complications
Traumatic intracranial hemorrhage
|
0.00%
0/83 • 28 weeks
|
1.2%
1/83 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
1.2%
1/83 • 28 weeks
|
2.4%
2/83 • 28 weeks
|
Other adverse events
| Measure |
LAU-7b
n=83 participants at risk
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.
|
Placebo
n=83 participants at risk
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.
|
|---|---|---|
|
Eye disorders
Delayed dark adaptation
|
26.5%
22/83 • 28 weeks
|
4.8%
4/83 • 28 weeks
|
|
Eye disorders
Night blindness
|
18.1%
15/83 • 28 weeks
|
2.4%
2/83 • 28 weeks
|
|
Eye disorders
Delayed light adaptation
|
12.0%
10/83 • 28 weeks
|
2.4%
2/83 • 28 weeks
|
|
Eye disorders
Glare
|
10.8%
9/83 • 28 weeks
|
7.2%
6/83 • 28 weeks
|
|
Eye disorders
Visual impairment
|
10.8%
9/83 • 28 weeks
|
2.4%
2/83 • 28 weeks
|
|
Eye disorders
Xanthopsia
|
8.4%
7/83 • 28 weeks
|
0.00%
0/83 • 28 weeks
|
|
Eye disorders
Photophobia
|
7.2%
6/83 • 28 weeks
|
4.8%
4/83 • 28 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
13.3%
11/83 • 28 weeks
|
7.2%
6/83 • 28 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
9.6%
8/83 • 28 weeks
|
8.4%
7/83 • 28 weeks
|
|
Gastrointestinal disorders
Nausea
|
7.2%
6/83 • 28 weeks
|
8.4%
7/83 • 28 weeks
|
|
General disorders
Fatigue
|
12.0%
10/83 • 28 weeks
|
8.4%
7/83 • 28 weeks
|
|
General disorders
Pyrexia
|
7.2%
6/83 • 28 weeks
|
4.8%
4/83 • 28 weeks
|
|
General disorders
Chest discomfort
|
6.0%
5/83 • 28 weeks
|
4.8%
4/83 • 28 weeks
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
26.5%
22/83 • 28 weeks
|
26.5%
22/83 • 28 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
15.7%
13/83 • 28 weeks
|
9.6%
8/83 • 28 weeks
|
|
Infections and infestations
Nasopharyngitis
|
7.2%
6/83 • 28 weeks
|
3.6%
3/83 • 28 weeks
|
|
Investigations
Glucose urine present
|
7.2%
6/83 • 28 weeks
|
2.4%
2/83 • 28 weeks
|
|
Investigations
Blood glucose increased
|
4.8%
4/83 • 28 weeks
|
6.0%
5/83 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.0%
5/83 • 28 weeks
|
3.6%
3/83 • 28 weeks
|
|
Nervous system disorders
Headache
|
16.9%
14/83 • 28 weeks
|
12.0%
10/83 • 28 weeks
|
|
Psychiatric disorders
Insomnia
|
4.8%
4/83 • 28 weeks
|
8.4%
7/83 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
27.7%
23/83 • 28 weeks
|
28.9%
24/83 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
13.3%
11/83 • 28 weeks
|
15.7%
13/83 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
12.0%
10/83 • 28 weeks
|
13.3%
11/83 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
8.4%
7/83 • 28 weeks
|
15.7%
13/83 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.2%
6/83 • 28 weeks
|
10.8%
9/83 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
3.6%
3/83 • 28 weeks
|
6.0%
5/83 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
1.2%
1/83 • 28 weeks
|
6.0%
5/83 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Acne
|
7.2%
6/83 • 28 weeks
|
6.0%
5/83 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.0%
5/83 • 28 weeks
|
3.6%
3/83 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.8%
4/83 • 28 weeks
|
9.6%
8/83 • 28 weeks
|
Additional Information
Dr Jean-Marie Houle, VP Clinical Development
Laurent Pharmaceuticals Inc.
Phone: 514-941-2313
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place