Lamellar ichthyosis (LI) Autosomal Recessive Ichthyosis with Lamellar Scale MedDRA version: 20.0 Level: LLT Classification code 10023686 Term: Lamellar ichthyosis System Organ Class: 100000004850
Conditions
Sponsors
Mayne Pharma LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. For Cohort A: subject is =18 years old; for Cohort B: subject is =12 years old. 2. Subject has known diagnosis of LI. 3. Subject has moderate to severe (IGA 3-4) LI on the IGA of LI severity 4. Subject has signed an ICF at Screening before any investigational procedures. Subjects =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Subject has any variant of ichthyosis other than LI or another disorder of keratinization including syndromic ichthyoses. 2. Subject has current moderate or severe stinging/burning at Screening. 3. Subject has an ongoing cutaneous infection or any other significant concomitant skin disease (other than the LI) which, in the investigator’s opinion, may interfere with the study assessments. 4. Subject with a known lipid disorder (hypertriglyceridemia >200 mg/dL, hypercholesterolemia >250 mg/dL) unless well controlled by stable doses of lipid-lowering agents for at least 6 months. 5. Subject was previously treated with trifarotene/CD5789, in an acne or ichthyosis study. 6. Subject has any other significant concomitant disease, or poorly controlled medical condition other than LI that in the investigator’s opinion may put him or her at risk if he or she takes part in the study, and/or that may interfere with the study assessments. 7. Subject has a medical condition that potentially alters bone metabolism (e.g., osteoporosis, thyroid dysfunction, Cushing syndrome, Crohn’s disease, or ulcerative colitis). 8. Subject is being treated for major depression disorder and/or has a history of major depression or suicide attempt requiring hospitalization, medications, and close psychiatric surveillance to prevent suicide attempts. 9. Subject with positive serology for hepatitis B surface antigen, hepatitis C, or are known to be HIV positive or to have AIDS at Screening. 10. Subject with any of the following laboratory values at Screening: a. Aspartate aminotransferase or alanine aminotransferase >1.5 × upper limit of normal defined by the laboratory b. Total bilirubin >1.1 mg/dL or, in case of Gilbert’s syndrome, total bilirubin >3 mg/dL c. Hemoglobin 400 × 109/L. 11. Subject has any clinically other significant abnormal laboratory value (hematology,chemistry, or urinalysis) at Screening that, in the investigator’s opinion, may put the subject at risk if he or she takes part in the study, and/or that may interfere with the study assessments. 12.Subject has had recent systemic malignancy (e.g., within 5 years) with exception of nonmelanoma skin cancer or cervical intraepithelial neoplasia of Grade 1 who are >6 months post-treatment 13. Subject has a history of long QT syndrome or clinically significant electrocardiogram (ECG) abnormalities, including clinically significant conduction disorders or significant arrhythmias, QTcF interval >450 ms, PR interval is not between 120 and 220 ms (inclusive), HR >100 bpm or 110 ms, or QT intervals that cannot be consistently analyzed. 14. Subject has a known allergy or sensitivity to any of the components of the investigational products. 15. Subject has been exposed to excessive ultraviolet (UV) radiations on the treated zones within 1 month before Baseline visit or who is planning intensive UV exposure during the study (e.g., occupational exposure to the sun, sunbathing, phototherapy, etc.). 16. Subject is inherently sensitive to sunlight. 17.Subject is unable or unwilling to stop use of topical or systemic retinoids 18. Subject is presumed to be abusing drugs or alcohol at Screening or Baseline Visits based on medical history or current clinical symptoms. 19. Subject is participating in another interventional clinical trial. 20. Subject is institutionalized 21.Subject is in any way relat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the safety and efficacy of 2 concentrations of trifarotene cream HE1 versus vehicle in adults and adolescents with moderate to severe autosomal recessive ichthyosis with lamellar scale, also known as lamellar ichthyosis (LI) after 12 weeks of treatment.;Secondary Objective: • To assess systemic exposure to trifarotene and its major metabolites after topical application of the investigational product (IP) on up to 90% body surface area (BSA) twice weekly. • To assess safety for up to 24 weeks of dosing with open-label trifarotene cream HE1 200 µg/g.;Primary end point(s): The proportion of subjects in each treatment group who experience successful resolution of LI where “success” is defined as clear/almost clear on treated areas and at least a 2-grade change from Baseline at Week 12/end-of-treatment (EOT) in the Double-blind Period on the 5-point IGA full body scale;Timepoint(s) of evaluation of this end point: The primary time point is Day 90 for double blind and day 194 for open label part of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The difference in mean scores between the active trifarotene cream HE1 and vehicle groups in the following assessment indices from Baseline through Week 12: -5-point Visual Index for Ichthyosis Severity (VIIS) for scaling from Baseline through Week 12 (overall 16 points for scaling, i.e. 0-4 points for 4 body areas: chest/abdomen, back, arms and legs) -Individual score for roughness (Scale: 0–4) overall -Palm/sole Assessment (Scale: 0–4) -Quality of life per Dermatology Life Quality Index (DLQI) and children’s DLQI (cDLQI) • The difference in proportion of subjects with presence of fissures on palms/soles (presence/absence, number of fissures, and pain associated with fissures on a 0 3 scale) at Week 12 between the active trifarotene cream HE1 and vehicle groups Exploratory endpoints: • The difference in mean ectropion (Ectropion Severity Score [ESS] of 0–8) scores between the active trifarotene cream HE1 and vehicle groups from Baseline through Week 12 • The difference in quality of life per EQ-5D-5L and EQ-5D-Y score between the active trifarotene cream HE1 and vehicle groups from Baseline through Week 12 Safety endpoints: • Reported serious adverse events (SAEs), treatment-emergent AEs (TEAEs), and changes in clinical laboratory tests, vital signs, physical examinations, and 12-lead ECGs • Local tolerability (Scale: 0–3 [none, mild, moderate, severe], determined by the investigator) for each body area (chest/abdomen, back, legs, arms, and face/neck). Pharmacokinetic endpoints: Plasma concentrations of CD5789 and its major metabolites will be measured.;Timepoint(s) of evaluation of this end point: secondary and exploratory efficacy endpoints as well as PK endpoints will be presented for all study visits (Day 1,14,30,60,90 and 104,120,150,180,194). Safety endpoints will be monitored throughout the entire study. | — |
Countries
Australia, Canada, France, Germany, Israel, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactPhoevos Hughes
Mayne Pharma LLC
Outcome results
None listed