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CompletedNCT03265288APPLAUDUpdated Oct 9, 2024Results posted

Study of LAU-7b in the Treatment of Cystic Fibrosis in Adults

A Phase 2 interventional study of LAU-7b and Placebo oral capsule in Cystic Fibrosis, sponsored by Laurent Pharmaceuticals Inc.. Completed at 40 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-10-09.

Sponsored by Laurent Pharmaceuticals Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
166
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Cystic Fibrosis

Keywords

  • Inflammation
  • Essential Fatty Acids
  • Inflammation resolution
  • Docosahexaenoic acid
  • Lung function
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
166 participants (actual)

Study arms

  • Experimental
    LAU-7b

    Active drug fenretinide (as LAU-7b capsules)

    Drug: LAU-7b

  • Placebo comparator
    Placebo

    Placebo oral capsule (as inactive capsules identical to active arm)

    Drug: Placebo oral capsule

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.

    Also known as: fenretinide

  • 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.

    Also known as: Placebo

05

What researchers measure

Primary outcomes

  1. 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

  2. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

Other outcomes

  1. 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

  2. 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

  3. 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

06

Results

Posted Oct 9, 2024
Limitations and caveats
The APPLAUD study started enrollment in November 2018 and was conducted through the COVID-19 pandemic and during market introduction of ETI (elexacaftor/tezacaftor/ivacaftor) in the participating countries. However, the study protocol and the statistical plan were amended to address the higher dropout rates caused by these two factors during the clinical trial and to allow enrolment of patients stabilized on ETI as their background CFTR modulator therapy.

Participant flow

Participant flow — Overall Study
MilestoneLAU-7bPlacebo
Started8383
Completed6071
Not completed2312
Withdrew: Adverse event01
Withdrew: Withdrawal by subject135
Withdrew: Drug withdrawn33
Withdrew: Any other reason73

Outcome measures

PrimaryAbsolute 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
Reported as:
Least squares mean · Change in FEV1 % predicted
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1%)
Change in FEV1 % predictedLAU-7bPlacebo
ITT population at Week 24-1.1774 (-2.5038 to 0.1490)-1.9489 (-3.2241 to -0.6738)
ITT population through Week 24-0.5417 (-1.5226 to 0.4392)-1.5470 (-2.5304 to -0.5637)
PP population through Week 24-0.3374 (-1.4987 to 0.8239)-1.5632 (-2.7333 to -0.3930)
ITT subgroup >=70% ppFEV1, at Week 24-1.4059 (-3.5506 to 0.7388)-4.0687 (-6.1289 to -2.0085)
ITT subgroup on CFTR modulators, at Week 24-0.3336 (-2.2467 to 1.5795)-1.7247 (-3.2954 to -0.1539)
ITT subgroup on ETI, at Week 24-0.7406 (-3.7472 to 2.2659)-1.8709 (-4.1669 to 0.4252)
Statistical analysis
  • LAU-7b vs Placebo · Mixed Model for Repeated Measures · p = 0.3449 (alpha is set to 0.05) · Least square means difference: 0.7716 · 95% CI -0.8397 to 2.3828A positive difference favours LAU-7b, a negative difference favours placebo.
  • LAU-7b vs Placebo · Mixed Model for Repeated Measures · p = 0.0667 (alpha is set to 0.05) · Least square means difference: 1.0053 · 95% CI -0.0700 to 2.0807A positive difference favours LAU-7b, a negative difference favours placebo.
  • LAU-7b vs Placebo · Mixed Model for Repeated Measures · p = 0.0486 (alpha is set to 0.05) · Least square means difference: 1.2258 · 95% CI 0.0078 to 2.4438A positive difference favours LAU-7b, a negative difference favours placebo.
  • LAU-7b vs Placebo · Mixed Model for Repeated Measures · p = 0.0687 (alpha is set to 0.05) · Least square means difference: 2.6628 · 95% CI -0.2069 to 5.5325A positive difference favours LAU-7b, a negative difference favours placebo.
  • LAU-7b vs Placebo · Mixed Model for Repeated Measures · p = 0.236 (alpha is set to 0.05) · Least square means difference: 1.391 · 95% CI -0.9220 to 3.7041A positive difference favours LAU-7b, a negative difference favours placebo.
  • LAU-7b vs Placebo · Mixed Model for Repeated Measures · p = 0.5323 (alpha is set to 0.05) · Least square means difference: 1.1302 · 95% CI -2.4447 to 4.7052A positive difference favours LAU-7b, a negative difference favours placebo.
PrimarySummary 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
Reported as:
Count of participants · Participants
Summary of Treatment Emergent Adverse Events With ≥ 10% Incidence
ParticipantsLAU-7bPlacebo
Subjects with at least one TEAE with ≥10% incidence7464
Mild highest reported severity2227
Moderate highest reported severity4543
Severe highest reported severity137
Life threatening00
Infective pulmonary exacerbation of cystic fibrosis3732
Cough2324
Delayed dark adaptation224
Night blindness152
Headache1410
Upper respiratory tract infections138
Hemoptysis1113
Diarrhoea116
Fatigue107
Delayed light adaptation102
Dyspnea1011
Glare96
Visual impairment92
Sputum increased713
SecondaryThe 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
Reported as:
Count of participants · Participants
The Proportion of Patients Achieving Normalization of the Arachidonic Acid, Docosahexaenoic Acid and Their Ratio in Phospholipids
ParticipantsLAU-7bPlacebo
Arachidonic acid (AA) normalization1525
Docosahexaenoic acid (DHA) normalization1618
AA/DHA ratio normalization2523
Statistical analysis
  • LAU-7b vs Placebo · Regression, Logistic · p = 0.1047 (alpha is set to 0.05) · Odds ratio (or): 0.5036 · 95% CI 0.2199 to 1.1532Odds ratio \< 1 means lower odds of normalization with LAU-7b, odds ratio \> 1 means higher odds of normalization with LAU-7b
  • LAU-7b vs Placebo · Regression, Logistic · p = 0.7596 (alpha is set to 0.05) · Odds ratio (or): 0.8773 · 95% CI 0.3793 to 2.0291Odds ratio \< 1 means lower odds of normalization with LAU-7b, odds ratio \> 1 means higher odds of normalization with LAU-7b
  • LAU-7b vs Placebo · Regression, Logistic · p = 0.8852 (alpha is set to 0.05) · Odds ratio (or): 1.0532 · 95% CI 0.5209 to 2.1296Odds ratio \< 1 means lower odds of normalization with LAU-7b, odds ratio \> 1 means higher odds of normalization with LAU-7b
SecondaryThe 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
Reported as:
Mean · FEV1 percent predicted change
The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial
FEV1 percent predicted changeLAU-7bPlacebo
Absolute change at Week 3-0.243 ± 5.110-1.494 ± 4.537
Absolute change at Week 70.280 ± 4.689-0.888 ± 3.968
Absolute change at Week 11-0.309 ± 4.268-0.871 ± 4.133
Absolute change at Week 15-0.508 ± 5.100-1.591 ± 4.389
Absolute change at Week 24-1.024 ± 4.286-1.759 ± 4.533
Absolute change at Week 28-1.539 ± 4.808-1.413 ± 4.457
SecondaryThe 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
Reported as:
Mean · FEV1 percent predicted change
The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial
FEV1 percent predicted changeLAU-7bPlacebo
Relative (%) change at Week 3-1.188 ± 8.632-2.341 ± 7.289
Relative (%) change at Week 70.561 ± 8.348-1.550 ± 6.829
Relative (%) change at Week 11-0.213 ± 7.124-1.277 ± 7.120
Relative (%) change at Week 15-0.924 ± 8.963-2.745 ± 7.425
Relative (%) change at Week 24-1.450 ± 6.966-2.652 ± 7.742
Relative (%) change at Week 28-2.388 ± 8.275-2.085 ± 7.525
SecondaryThe 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
Reported as:
Median · days
The Time to First Protocol-Defined Pulmonary Exacerbation
daysLAU-7bPlacebo
The Time to First Protocol-Defined Pulmonary ExacerbationNA (NA to NA)NA (NA to NA)
Statistical analysis
  • LAU-7b vs Placebo · Log Rank · p = 0.3025
SecondaryThe 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
Reported as:
Mean · Events per subject
The Number Per Subject of Protocol-Defined Pulmonary Exacerbations (PEx) During the Trial
Events per subjectLAU-7bPlacebo
Protocol-Defined IV-treated PEx events per subject0.16 ± 0.3980.10 ± 0.335
All IV-treated PEx events per subject0.24 ± 0.4580.18 ± 0.566
All IV- or Oral antibiotics-treated PEx events per subject0.53 ± 0.7210.47 ± 0.817
Statistical analysis
  • LAU-7b vs Placebo · Regression, Cox · p = 0.3366 (alpha is set to 0.05) · Risk ratio (rr): 1.55 · 95% CI 0.63 to 3.80Odds ratio \< 1 means lower odds of a pulmonary exacerbation with LAU-7b, odds ratio close to 1 means similar odds of a pulmonary exacerbation for LAU-7b and placebo, odds ratio \> 1 means higher odds of a pulmonary exacerbation with LAU-7b
  • LAU-7b vs Placebo · Regression, Cox · p = 0.3936 (alpha is set to 0.05) · Risk ratio (rr): 1.34 · 95% CI 0.68 to 2.64Odds ratio \< 1 means lower odds of a pulmonary exacerbation with LAU-7b, odds ratio close to 1 means similar odds of a pulmonary exacerbation for LAU-7b and placebo, odds ratio \> 1 means higher odds of a pulmonary exacerbation with LAU-7b
  • LAU-7b vs Placebo · Regression, Cox · p = 0.5011 (alpha is set to 0.05) · Risk ratio (rr): 1.16 · 95% CI 0.75 to 1.79Odds ratio \< 1 means lower odds of a pulmonary exacerbation with LAU-7b, odds ratio close to 1 means similar odds of a pulmonary exacerbation for LAU-7b and placebo, odds ratio \> 1 means higher odds of a pulmonary exacerbation with LAU-7b
SecondaryThe 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
Reported as:
Median · days
The Time to First Change and Usage of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)
daysLAU-7bPlacebo
The Time to First Change and Usage of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)NA (NA to NA)NA (NA to NA)
Statistical analysis
  • LAU-7b vs Placebo · Log Rank · p = 0.1955
SecondaryUsage (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
Reported as:
Mean · Number of IV antibiotic treatments
Usage (Number of Antibiotic Treatments) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)
Number of IV antibiotic treatmentsLAU-7bPlacebo
Usage (Number of Antibiotic Treatments) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)0.53 ± 1.090.41 ± 1.32
Statistical analysis
  • LAU-7b vs Placebo · Poisson regression · p = 0.1909 (alpha is set to 0.05) · Risk ratio (rr): 1.35 · 95% CI 0.86 to 2.12Odds ratio \< 1 means lower odds of an antibiotic treatment with LAU-7b, odds ratio \> 1 means higher odds of an antibiotic treatment with LAU-7b
SecondaryUsage (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
Reported as:
Mean · Days of IV antibiotics
Usage (Days) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)
Days of IV antibioticsLAU-7bPlacebo
Usage (Days) of Antibiotic (Other Than Chronic Inhaled Antibiotics Already Started Prior to Trial or Oral Chronic Azithromycin)3.8 ± 7.503.5 ± 14.94
Statistical analysis
  • LAU-7b vs Placebo · Poisson regression · p = 0.7473 (alpha is set to 0.05) · Risk ratio (rr): 1.11 · 95% CI 0.60 to 2.04Odds ratio \< 1 means lower odds in terms of days of antibiotics with LAU-7b, odds ratio close to 1 means similar odds in terms of days of antibiotics with LAU-7b or placebo, odds ratio \> 1 means higher odds in terms of days of antibiotics with LAU-7b
SecondaryThe 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
Reported as:
Mean · Change in mg/L
The Change From Baseline of Systemic Markers of Inflammation in Blood
Change in mg/LLAU-7bPlacebo
Absolute change from baseline of C-reactive protein at Week 24 ITT Population-1.197 ± 7.9042.532 ± 10.650
Absolute change from baseline of calprotectin at Week 24, ITT population-27 ± 962478 ± 2088
Absolute change from baseline of C-reactive protein at Week 24 PP Population-1.216 ± 7.9872.532 ± 10.654
Absolute change from baseline of calprotectin at Week 24, PP population-18 ± 970478 ± 2088
Statistical analysis
  • LAU-7b vs Placebo · Mixed Model for Repeated Measures · p = 0.0822 (alpha is set to 0.05) · Least squares means difference: -2.890 · 95% CI -6.154 to 0.374A negative difference favours LAU-7b, a positive difference favours placebo
  • LAU-7b vs Placebo · Mixed Model for Repeated Measures · p = 0.0603 (alpha is set to 0.05) · Least squares means difference: -576 · 95% CI -1177 to 25.4A negative difference favours LAU-7b, a positive difference favours placebo
  • LAU-7b vs Placebo · Mixed Model for Repeated Measures · p = 0.0287 (alpha is set to 0.05) · Least square means difference: -3.853 · 95% CI -7.297 to -0.408A negative difference favours LAU-7b, a positive difference favours placebo
  • LAU-7b vs Placebo · Mixed Model for Repeated Measures · p = 0.0459 (alpha is set to 0.05) · Least square means difference: -620 · 95% CI -1228 to 12A negative difference favours LAU-7b, a positive difference favours placebo
SecondaryThe 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
Reported as:
Mean · Change in kg
The Change From Screening of the Body Weight
Change in kgLAU-7bPlacebo
The Change From Screening of the Body Weight-0.43 ± 2.410.14 ± 1.96
Statistical analysis
  • LAU-7b vs Placebo · Mixed Model for Repeated Measures · p = 0.1006 (alpha is set to 0.05) · Least squares means difference: -0.39 · 95% CI -0.86 to 0.08
SecondaryThe 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
Reported as:
Mean · Change in kg/m2
The Change From Screening of the Body Mass Index (BMI)
Change in kg/m2LAU-7bPlacebo
The Change From Screening of the Body Mass Index (BMI)-0.162 ± 0.9220.037 ± 0.706
Statistical analysis
  • LAU-7b vs Placebo · Mixed Model for Repeated Measures · p = 0.1246 (alpha is set to 0.05) · Least squares means difference: -0.137 · 95% CI -0.312 to 0.038
SecondaryThe 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
Reported as:
Mean · CFU*weeks/mL
The Overall Change From Screening of the Pseudomonas Aeruginosa Density (Colony Forming Units) in the Sputum
CFU*weeks/mLLAU-7bPlacebo
The Overall Change From Screening of the Pseudomonas Aeruginosa Density (Colony Forming Units) in the Sputum17681448107 ± 3305010577510218800226 ± 16808101968
Statistical analysis
  • LAU-7b vs Placebo · ANOVA · p = 0.7640 (alpha is set to 0.05)
SecondaryThe 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
Reported as:
Mean · Change of units on a scale
The Impact (From Baseline) on Overall Health, Daily Life, Perceived Well-being and Symptoms Measured With the Cystic Fibrosis Questionnaire-Revised (CFQ-R)
Change of units on a scaleLAU-7bPlacebo
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 ± 20.280.235 ± 11.44
Statistical analysis
  • LAU-7b vs Placebo · Mixed Model for Repeated Measures · p = 0.2996 (alpha is set to 0.05) · Least squares means difference: -2.758 · 95% CI -7.998 to 2.482
SecondaryThe 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
Reported as:
Mean · umol/L
The Change in Metabolipidomic Profile and in Markers of Oxidative Stress in Blood
umol/LLAU-7bPlacebo
11-Hydroxy Eicosatetraenoic Acid-0.0195 ± 0.135590.0187 ± 0.08397
12-Hydroxy Eicosatetraenoic Acid-0.00445 ± 0.491341-0.01181 ± 0.820744
15-Hydroxy Eicosapentaenoic Acid0.00069 ± 0.0258280.02028 ± 0.059147
19,20-diHydroxy Docosapentaenoic Acid0.16447 ± 0.8657880.06606 ± 0.568695
8-Hydroxy Eicosatetraenoic Acid-0.00744 ± 0.0934980.01879 ± 0.088266
Thiobarbituric Acid Reactive Substances-0.0504 ± 0.799400.0406 ± 1.19656
Nitrotyrosine (NT3)-1.57 ± 72.96410.35 ± 146.824
Other pre-specifiedThe 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

No measurements were reported for this outcome.

Other pre-specifiedThe 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
Reported as:
Mean · Change in ug/L
The Change From Baseline of Systemic Bone Formation and Resorption Biomarkers
Change in ug/LLAU-7bPlacebo
Aminoterminal Propeptide-5.0 ± 14.90-4.5 ± 16.97
C-Telopeptide-0.012 ± 0.20920.015 ± 0.1857
Osteocalcin-1.46 ± 6.1810.57 ± 5.703
Other pre-specifiedThe 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
Reported as:
Mean · Z-score
The Change From Baseline of Bone Mineral Density
Z-scoreLAU-7bPlacebo
The Change From Baseline of Bone Mineral Density-0.18 ± 0.690.09 ± 0.28

Adverse events

Collected over 28 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
LAU-7b0/83 (0%)20/83 (24.1%)80/83 (96.4%)
Placebo0/83 (0%)15/83 (18.1%)79/83 (95.2%)
Most frequent serious events
Showing 10 of 11
Most frequent serious events
EventLAU-7bPlacebo
Infective pulmonary exacerbation of cystic fibrosisInfections and infestations15/8310/83
Distal intestinal obstruction syndromeGastrointestinal disorders2/832/83
AppendicitisInfections and infestations2/830/83
HemoptysisRespiratory, thoracic and mediastinal disorders1/832/83
Loss of visual contrast sensitivityEye disorders1/830/83
ConstipationGastrointestinal disorders1/830/83
Small intestinal obstructionGastrointestinal disorders0/831/83
InfluenzaInfections and infestations1/830/83
Pneumonia staphylococcalInfections and infestations1/830/83
PneumoniaInfections and infestations0/831/83
Most frequent other events
Showing 10 of 31
Most frequent other events
EventLAU-7bPlacebo
CoughRespiratory, thoracic and mediastinal disorders23/8324/83
Delayed dark adaptationEye disorders22/834/83
Infective pulmonary exacerbation of cystic fibrosisInfections and infestations22/8322/83
Night blindnessEye disorders15/832/83
HeadacheNervous system disorders14/8310/83
Upper respiratory tract infectionInfections and infestations13/838/83
HemoptysisRespiratory, thoracic and mediastinal disorders11/8313/83
Sputum increasedRespiratory, thoracic and mediastinal disorders7/8313/83
DiarrheaGastrointestinal disorders11/836/83
DyspneaRespiratory, thoracic and mediastinal disorders10/8311/83

Baseline characteristics

Age, Continuous
Age, Continuous(years)LAU-7bPlaceboTotal
Mean31.5 ± 10.7033.9 ± 12.9532.7 ± 11.90
Age, Customized
Age, Customized(Participants)LAU-7bPlaceboTotal
<=25 years292655
>25 years5457111
Sex: Female, Male
Sex: Female, Male(Participants)LAU-7bPlaceboTotal
Female504999
Male333467
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)LAU-7bPlaceboTotal
Hispanic or Latino729
Not Hispanic or Latino7681157
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)LAU-7bPlaceboTotal
American Indian or Alaska Native011
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American235
White8178159
More than one race000
Unknown or Not Reported011
Region of Enrollment
Region of Enrollment(participants)LAU-7bPlaceboTotal
Canada242246
United States485199
Australia111021
Weight (kg), Mean (SD)
Weight (kg), Mean (SD)(kg)LAU-7bPlaceboTotal
Mean63.88 ± 12.21364.53 ± 14.32964.20 ± 13.277
BMI (kg/m2), Mean (SD)
BMI (kg/m2), Mean (SD)(kg/m2)LAU-7bPlaceboTotal
Mean23.34 ± 3.35423.39 ± 4.09923.36 ± 3.734

2 further baseline measures are reported on the registry.

07

Study locations

40 sites
  • Long Beach Memorial Medical Center
    Long Beach, California 90806, United States
  • Children's Hospital Los Angeles
    Los Angeles, California 90227, United States
  • UC Davis Medical Center, Division of Pulmonary & Critical Care Medicine
    Sacramento, California 95817, United States
  • Children's National Medical Center
    Washington, District of Columbia 20010, United States
  • Division of pulmonary, critical care and sleep medicine, University of Florida
    Gainesville, Florida 32610, United States
  • Memorial Healthcare System, Joe DiMaggio Children's Hospital Cystic Fibrosis & Pulmonary Center
    Hollywood, Florida 33021, United States
  • Avanza Medical Research Center
    Pensacola, Florida 32603, United States
  • St-Luke's CF Center of Idaho
    Boise, Idaho 83712, United States
  • Riley Hospital for Children
    Indianapolis, Indiana 46202, United States
  • University of Kansas Medical Center
    Kansas City, Kansas 66103, United States
  • Maine Medical Center Cystic Fibrosis Research
    Portland, Maine 04102, United States
  • University of Michigan Health System
    Ann Arbor, Michigan 48109, United States
  • Wayne State University, Harper University Hospital
    Detroit, Michigan 48201, United States
  • The Minnesota Cystic Fibrosis Center, University of Minnesota
    Minneapolis, Minnesota 55455, United States
  • Washington University Medical School
    Saint Louis, Missouri 63110, United States
  • Morristown Medical Center, NJ Adult Cystic Fibrosis Center
    Morristown, New Jersey 07962, United States
  • Rutgers University Clinical Research Center, RW Johnson University Hospital
    New Brunswick, New Jersey 08901, United States
  • Albany Medical College
    Albany, New York 12208, United States
  • University Hospitals Cleveland Medical Center, Rainbow Babies and Children's Hospital
    Cleveland, Ohio 44106, United States
  • Nationwide Children's Hospital
    Columbus, Ohio 43205, United States
  • University of Oklahoma Health Sciences Center
    Oklahoma City, Oklahoma 73104, United States
  • Cystic Fibrosis Center, Doernbecher Children's Hospital, Oregon Health & Science University
    Portland, Oregon 97239, United States
  • Children's Hospital of Pittsburgh of UPMC
    Pittsburgh, Pennsylvania 15224, United States
  • Medical University of South Carolina
    Charleston, South Carolina 29425, United States
  • University of Utah
    Salt Lake City, Utah 84132, United States
  • Virginia Commonwealth University
    Richmond, Virginia 23298, United States
  • Medical College of Wisconsin, Div of Pulmonary and Critical Care Medicine
    Milwaukee, Wisconsin 53226, United States
  • Respiratory Medicine, John Hunter Hospital
    New Lambton Heights, New South Wales 2305, Australia
  • Department of Respiratory Medicine, Royal Prince Alfred Hospital
    Sydney, New South Wales 2050, Australia
  • Department of Respiratory and Sleep Medicine, Westmead Hospital
    Westmead, New South Wales 2145, Australia
  • Mater Misericordiae Ltd
    Brisbane, Queensland 4101, Australia
  • Monash Lung and Sleep, Monash Health
    Clayton, Victoria 3168, Australia
  • The Alfred Hospital
    Melbourne, Victoria 3004, Australia
  • Institute of Respiratory Health, Harry Perkins Institute
    Nedlands, Western Australia 6009, Australia
  • Pacific Lung Research Institute at St. Paul's Hospital
    Vancouver, British Columbia V6Z 1Y6, Canada
  • The Ottawa Hospital Center for Practice-Changing Research
    Ottawa, Ontario K1H 8L6, Canada
  • Centre d'études cliniques CIUSS SLJ, Hôpital Chicoutimi
    Chicoutimi, Quebec G7H 5H6, Canada
  • Centre Hospitalier de l'Université de Montréal
    Montréal, Quebec H2X2P1, Canada
  • McGill University Health Center
    Montréal, Quebec H4A 3J1, Canada
  • Centre de recherche de l'institut Universitaire de Cardiologie et de Pneumologie de Québec
    Québec City, Quebec G1V 4G5, Canada
08

References and documents

Study documents

  • Study protocol · Jul 31, 2019
  • Statistical analysis plan · Sep 3, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03265288
Lead sponsor
Laurent Pharmaceuticals Inc.
Collaborators
Cystic Fibrosis Foundation
Responsible party
Sponsor
First posted
Aug 29, 2017
Start date
Nov 5, 2018
Primary completion
Sep 15, 2021
Completion
Sep 15, 2021
Results posted
Oct 9, 2024
Last update
Oct 9, 2024

Study contacts

Larry C Lands, MD PhD
study chair · McGill Uinversity Health Centre
Michael W Konstan, MD
study chair · Rainbow Babies and Children's Hospital/ University Hospitals Cleveland Medical Center

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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