Study of LAU-7b in the Treatment of Cystic Fibrosis in Ad... | NCT03265288

Status Module

Name	Class
Cystic Fibrosis Foundation	OTHER

Description Module

Label	Type	Description	Intervention Names
LAU-7b	Experimental	Active drug fenretinide (as LAU-7b capsules)	Drug: LAU-7b
Placebo	Placebo Comparator	Placebo oral capsule (as inactive capsules identical to active arm)	Drug: Placebo oral capsule

Name	Type	Description	Arm Group Labels	Other Names
LAU-7b	Drug	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.	LAU-7b

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	From baseline to 24 weeks
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	From Baseline to 28 weeks

Secondary Outcomes

Measure	Description	Time Frame
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.

Other Outcomes

Measure	Description	Time Frame
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.	From baseline to 28 weeks

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
Larry C Lands, MD PhD	McGill Uinversity Health Centre	Study Chair
Michael W Konstan, MD	Rainbow Babies and Children's Hospital/ University Hospitals Cleveland Medical Center	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Long Beach Memorial Medical Center		Long Beach	California	90806	United States
Children's Hospital Los Angeles

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	Placebo

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 31, 2019	Aug 1, 2024

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00031.5± 10.70 BG00133.9± 12.95 BG00232.7± 11.90

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

<=25 years

Title	Measurements
	BG00029 BG00126 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00050 BG00149 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0007 BG0012 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0011 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Canada

Title	Measurements
	BG00024 BG00122 BG002

Weight (kg), Mean (SD)

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00063.88± 12.213 BG00164.53± 14.329 BG002

BMI (kg/m2), Mean (SD)

Mean

Standard Deviation

kg/m2

Title

Denominators

Categories

Title	Measurements
	BG00023.34± 3.354 BG00123.39± 4.099 BG002

Number of PEx in the previous year, (Mean (SD)

Mean

Standard Deviation

Pulmonary Exacerbation

Title

Denominators

Categories

Title	Measurements
	BG0002.3± 1.77 BG0012.1± 1.54 BG002

FEV1 percent predicted at Baseline

Mean

Standard Deviation

percent predicted

Title

Denominators

Categories

Title	Measurements
	BG00063.2± 16.77 BG00162.3± 15.13 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

intent to treat population (ITT) and per-protocol population (PP)

Posted

Least Squares Mean

95% Confidence Interval

Change in FEV1 % predicted

From baseline to 24 weeks

ID	Title	Description
OG000	LAU-7b	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.
OG001	Placebo	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.

Units	Counts
Participants	OG00083 OG00183

Title

Denominators

Categories

ITT population at Week 24

- ParticipantsOG00083
- ParticipantsOG00183

Title	Measurements
	OG000-1.1774(-2.5038 to 0.1490)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Primary analysis of the treatment effect at the Week 24 visit on the intent to treat population (ITT) Null hypothesis is no treatment difference	Mixed Model for Repeated Measures		0.3449	alpha is set to 0.05	Least square means difference	0.7716			2-Sided	95	-0.8397	2.3828			A positive difference favours LAU-7b, a negative difference favours placebo.		Superiority

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

safety population

Posted

Count of Participants

Participants

From Baseline to 28 weeks

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

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.

Intent to treat population with analytical results at any sampling visit up to 28 weeks

Posted

Count of Participants

Participants

From baseline to 28 weeks

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Secondary

The Absolute Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial

Intent to treat population (ITT)

Posted

Mean

Standard Deviation

FEV1 percent predicted change

From baseline to 3, 7, 11, 15, 24 and 28 weeks into the trial

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Secondary

The Relative (%) Change in FEV1 Percent Predicted at 3, 7, 11, 15, 24 and 28 Weeks Into the Trial

Intent to treat population (ITT)

Posted

Mean

Standard Deviation

FEV1 percent predicted change

From baseline to 3, 7, 11, 15, 24 and 28 weeks into the trial

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

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.

Posted

Median

95% Confidence Interval

days

From baseline to 28 weeks

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

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.

Posted

Mean

Standard Deviation

Events per subject

From baseline to 28 weeks

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

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.

Posted

Median

95% Confidence Interval

days

From baseline to 28 weeks

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

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.

Posted

Mean

Standard Deviation

Number of IV antibiotic treatments

From baseline to 28 weeks

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

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.

Posted

Mean

Standard Deviation

Days of IV antibiotics

From baseline to 28 weeks

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

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.

Intent to treat population (ITT) and per-protocol population (PP)

Posted

Mean

Standard Deviation

Change in mg/L

Change from baseline to Week 24

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

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.

Posted

Mean

Standard Deviation

Change in kg

From screening to 28 weeks

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

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.

Intent to treat (ITT)

Posted

Mean

Standard Deviation

Change in kg/m2

From screening to 28 weeks

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

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.

Intent to treat population (ITT) with samples at screening and post-screening timepoints, and at sites able to obtain sputum samples

Posted

Mean

Standard Deviation

CFU*weeks/mL

From screening to Week 24

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

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.

Absolute change of CFQ-R Respiratory sub-score, from Baseline to Week 24. Intent to treat population (ITT)

Posted

Mean

Standard Deviation

Change of units on a scale

From baseline to 24 weeks

ID	Title	Description
OG000	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.
OG001	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.

Units

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.

Absolute change from Baseline at Week 24. Intent to treat population (ITT) in subjects with samples analyzed at baseline and at Week 24

Posted

Mean

Standard Deviation

umol/L

From baseline to 24 weeks

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

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.

Only very few subjects got sampled pre- and post-pulmonary exacerbation, rendering this data anecdotic. No outcome measure is presented.

Posted

From baseline to 28 weeks

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

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.

Absolute change from Baseline at Week 24. Intent to treat population (ITT)

Posted

Mean

Standard Deviation

Change in ug/L

Baseline and 24 weeks

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

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.

Absolute change from Baseline at Week 24. Intent to treat population (ITT) in subjects volunteering to undergo bone density measurement

Posted

Mean

Standard Deviation

Z-score

Baseline and 28 weeks

ID	Title	Description
OG000	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.
OG001	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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Loss of visual contrast sensitivity	Eye disorders	MedDRA (11.0)	Non-systematic Assessment	EG0001 affected83 at risk EG0010 affected83 at risk
Distal intestinal obstruction syndrome	Gastrointestinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG0002 affected83 at risk EG0012 affected83 at risk
Constipation	Gastrointestinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG0001 affected83 at risk EG0010 affected83 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG0000 affected83 at risk EG0011 affected83 at risk
Infective pulmonary exacerbation of cystic fibrosis	Infections and infestations	MedDRA (11.0)	Non-systematic Assessment	EG00015 affected83 at risk EG00110 affected83 at risk
Appendicitis	Infections and infestations	MedDRA (11.0)	Non-systematic Assessment	EG0002 affected83 at risk EG0010 affected83 at risk
Influenza	Infections and infestations	MedDRA (11.0)	Non-systematic Assessment	EG0001 affected83 at risk EG0010 affected83 at risk
Pneumonia staphylococcal	Infections and infestations	MedDRA (11.0)	Non-systematic Assessment	EG0001 affected83 at risk EG0010 affected83 at risk
Pneumonia	Infections and infestations	MedDRA (11.0)	Non-systematic Assessment	EG0000 affected83 at risk EG0011 affected83 at risk
Traumatic intracranial hemorrhage	Injury, poisoning and procedural complications	MedDRA (11.0)	Non-systematic Assessment	EG0000 affected83 at risk EG0011 affected83 at risk
Hemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG0001 affected83 at risk EG0012 affected83 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Delayed dark adaptation	Eye disorders	MedDRA (11.0)	Non-systematic Assessment	EG00022 affected83 at risk EG0014 affected83 at risk
Night blindness	Eye disorders	MedDRA (11.0)	Non-systematic Assessment	EG00015 affected83 at risk EG0012 affected83 at risk
Delayed light adaptation	Eye disorders	MedDRA (11.0)	Non-systematic Assessment	EG00010 affected83 at risk EG0012 affected83 at risk
Glare	Eye disorders	MedDRA (11.0)	Non-systematic Assessment	EG0009 affected83 at risk EG0016 affected83 at risk
Visual impairment	Eye disorders	MedDRA (11.0)	Non-systematic Assessment	EG0009 affected83 at risk EG0012 affected83 at risk
Xanthopsia	Eye disorders	MedDRA (11.0)	Non-systematic Assessment	EG0007 affected83 at risk EG0010 affected83 at risk
Photophobia	Eye disorders	MedDRA (11.0)	Non-systematic Assessment	EG0006 affected83 at risk EG0014 affected83 at risk
Diarrhea	Gastrointestinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG00011 affected83 at risk EG0016 affected83 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG0008 affected83 at risk EG0017 affected83 at risk
Nausea	Gastrointestinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG0006 affected83 at risk EG0017 affected83 at risk
Fatigue	General disorders	MedDRA (11.0)	Non-systematic Assessment	EG00010 affected83 at risk EG0017 affected83 at risk
Pyrexia	General disorders	MedDRA (11.0)	Non-systematic Assessment	EG0006 affected83 at risk EG0014 affected83 at risk
Chest discomfort	General disorders	MedDRA (11.0)	Non-systematic Assessment	EG0005 affected83 at risk EG0014 affected83 at risk
Infective pulmonary exacerbation of cystic fibrosis	Infections and infestations	MedDRA (11.0)	Non-systematic Assessment	EG00022 affected83 at risk EG00122 affected83 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (11.0)	Non-systematic Assessment	EG00013 affected83 at risk EG0018 affected83 at risk
Nasopharyngitis	Infections and infestations	MedDRA (11.0)	Non-systematic Assessment	EG0006 affected83 at risk EG0013 affected83 at risk
Glucose urine present	Investigations	MedDRA (11.0)	Non-systematic Assessment	EG0006 affected83 at risk EG0012 affected83 at risk
Blood glucose increased	Investigations	MedDRA (11.0)	Non-systematic Assessment	EG0004 affected83 at risk EG0015 affected83 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Non-systematic Assessment	EG0005 affected83 at risk EG0013 affected83 at risk
Headache	Nervous system disorders	MedDRA (11.0)	Non-systematic Assessment	EG00014 affected83 at risk EG00110 affected83 at risk
Insomnia	Psychiatric disorders	MedDRA (11.0)	Non-systematic Assessment	EG0004 affected83 at risk EG0017 affected83 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG00023 affected83 at risk EG00124 affected83 at risk
Hemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG00011 affected83 at risk EG00113 affected83 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG00010 affected83 at risk EG00111 affected83 at risk
Sputum increased	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG0007 affected83 at risk EG00113 affected83 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG0006 affected83 at risk EG0019 affected83 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG0003 affected83 at risk EG0015 affected83 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG0001 affected83 at risk EG0015 affected83 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA (11.0)	Non-systematic Assessment	EG0006 affected83 at risk EG0015 affected83 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (11.0)	Non-systematic Assessment	EG0005 affected83 at risk EG0013 affected83 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (11.0)	Non-systematic Assessment	EG0004 affected83 at risk EG0018 affected83 at risk

ID	Term
D010182	Pancreatic Diseases
D004066	Digestive System Diseases
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D007232	Infant, Newborn, Diseases
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D012176	Retinoids
D002338	Carotenoids
D011090	Polyenes
D000475	Alkenes
D006839	Hydrocarbons, Acyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D053138	Cyclohexenes
D003510	Cyclohexanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D013729	Terpenes
D010860	Pigments, Biological
D001685	Biological Factors

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	0	83	20	83	80	83
EG001	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.	0	83	15	83	79	83