COVID-19 studies are our top priority. For all other trials, there is a 4-week delay in processing a trial submitted/resubmitted to the ANZCTR and additional delays for updates of registered trials. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03738800




Registration number
NCT03738800
Ethics application status
Date submitted
24/10/2018
Date registered
13/11/2018
Date last updated
17/03/2020

Titles & IDs
Public title
A Safety, Efficacy and Systemic Exposure Study of CD5789 Cream in Adults and Adolescents With Lamellar Ichthyosis
Scientific title
A Phase 2 Randomized, Multicenter, Doubleblind, Vehicle Controlled, 12 Week, Safety, Efficacy & Systemic Exposure Study Followed by a 12 Week Open-label Extension of CD5789 in Adults and Adolescents With Autosomal Recessive Ichthyosis With Lamellar Scale
Secondary ID [1] 0 0
18-ICH-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lamellar Ichthyosis 0 0
Condition category
Condition code
Skin 0 0 0 0
Other skin conditions
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CD5789 Cream 200 µg/g
Treatment: Drugs - CD5789 Cream 100 µg/g
Treatment: Drugs - CD5789 Cream Vehicle

Experimental: CD5789 Cream 200 µg/g - CD5789 200 µg/g, topical, 50g

Experimental: CD5789 Cream 100 µg/g - CD5789 100 µg/g, topical, 50g

Placebo Comparator: CD5789 Cream Vehicle - CD5789 Cream Vehicle, topical, 50g


Treatment: Drugs: CD5789 Cream 200 µg/g
A fixed dose (determined at Visit 1) of 200 µg/g applied topically twice weekly to up to 90% BSA

Treatment: Drugs: CD5789 Cream 100 µg/g
A fixed dose (determined at Visit 1) of 100 µg/g applied topically twice weekly to up to 90% BSA

Treatment: Drugs: CD5789 Cream Vehicle
A fixed dose (determined at Visit 1) applied topically twice weekly, up to 36 g per dose up to 90% BSA

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The number of subjects in each treatment group who experience successful resolution of LI. - The number of subjects in each treatment group who experience successful resolution of LI where "success" is defined as clear/almost clear overall and at least a 50% reduction from Baseline at Week 12/end-of-treatment (EOT) in the Double-blind Period on the overall 16-point VIIS for scaling (i.e., 0-4 points on each of the 4 body areas: chest/abdomen, back, arms, and legs).
Timepoint [1] 0 0
12 weeks
Secondary outcome [1] 0 0
The difference in mean scores using Individual score for roughness - The amount of roughness of the skin will be measured on a 5-point scale. 0 (Clear) Smooth skin
(Almost Clear) Hardly palpably roughness
(Mild) Mild roughness (fine sand paper-like)
(Moderate) Moderate, coarse roughness (coarse sand paper-like)
(Severe) Very coarse skin (broken cornflakes-like)
Timepoint [1] 0 0
12 weeks
Secondary outcome [2] 0 0
The difference in mean scores using Palm Sole Assessment - Thickening of the skin on the palms and soles will be measured on a 5-point scale:
0 (Clear) No thickening, no roughness, no fissure
(Almost Clear) Only slight thickening, minimal to no roughness, no fissures
(Mild) Some thickening, mild roughness on palpation, few fissures may be present
(Moderate) Substantial and diffuse thickening, coarse roughness on palpation may be present, fissures may be present
(Severe) Very thickened and rough skin, numerous fissures
Timepoint [2] 0 0
12 weeks
Secondary outcome [3] 0 0
The difference in proportion of subjects with presence of fissures between the active and vehicle groups - Fissuring will be assessed by recording the presence or absence of fissures, the number of fissures present, and the pain associated with each fissure. The subject will assess pain associated with fissures as ranging from 0-3 (none, mild, moderate, severe) at week 12 between the active trifarotene cream HE1 and vehicle groups
Timepoint [3] 0 0
12 weeks
Secondary outcome [4] 0 0
Quality of life measurement per Dermatology Life Quality Index (DLQI) - The DLQI, or the Dermatology Quality of Life Index, is a dermatology-specific Quality of Life instrument. It is a simple 10-question validated questionnaire with 6 domains (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment); higher scores indicate poorer quality of life. Responses collected are on a scale of 0-3 depending on the question relevance to the subject.
Response (Score) Very much (scored 3) A lot (scored 2) A little (scored 1) Not at all (scored 0) Not relevant (scored 0) A minimum score of 0 and maximum score of 30 is obtained by summing the score of each question. The higher the score, the more quality of life is impaired.
0-1 = no effect at all on patient's life 2-5 = small effect on patient's life 6-10 = moderate effect on patient's life 11-20 = very large effect on patient's life 21-30 = extremely large effect on patient's life
Timepoint [4] 0 0
12 weeks
Secondary outcome [5] 0 0
5-point Visual Index for Ichthyosis Severity (VIIS) - The amount of scaling will be measured on a 5-point scale. 0 (Clear) No scaling
(Almost Clear) Very fine, non-coalescent scales
(Mild) Small and thin, non-coalescent scales
(Moderate) Large and rather thick scales starting to coalesce
(Severe) Very large, adherent, coalescent and very thick scales
Timepoint [5] 0 0
12 weeks

Eligibility
Key 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 (IGA3-4) LI on the IGA of LI severity.

4. Subject has signed an ICF at Screening before any investigational procedures. Subjects
<18 years of age (or Age of Majority) must sign an assent form in conjunction with an
ICF signed by the parent/legal representative.

5. Subject who is participating in photography has signed a photography ICF.

6. Subject who is participating in the optional PK substudy has signed a PK ICF.

7. Subject is not of childbearing potential, i.e., a female who has not yet begun
menstruating or who is postmenopausal (absence of menstrual bleeding for 1 year before
Baseline, without any other medical reason, hysterectomy or bilateral oophorectomy),
OR

- Subject is a woman of childbearing potential (WOCBP) or a male subject with
sexual partners capable of reproduction who agrees to use 2 effective forms of
contraception during the study and for at least 1 month after the last study drug
application. The 2 authorized forms of contraception are condom used with 1 of
the following methods of contraception:

- bilateral tubal ligation

- combined oral contraceptives (estrogens and progesterone) or implanted or
injectable contraceptives with a stable dose for at least 1 month before Baseline

- hormonal intrauterine device (IUD) inserted at least 1 month before Baseline OR
Agrees to abstain from sex during study participation and for 1 month after the
last application of study drug and to use a highly effective contraceptive as
backup if he or she becomes sexually active during the study.

AND Male subjects may not donate sperm during the study and for at least 1 month after
the last study drug application.

Note: Subjects who are premenstrual at Screening but begin menses during the study
should follow the pregnancy testing schedule for WOCBP and must abstain from sexual
intercourse while in the study and for at least 1 month after the last study drug
application.

8. Women of child-bearing potential must be nonlactating and have negative pregnancy test
results at Screening (serum) and on Day 1 before study drug administration (urine).

9. Subject is reliable and capable of adhering to the protocol and visit schedule, in the
investigator's judgment, and has signed informed consent/assent, as applicable.

10. Subject is taking no more than 3500 IU/day Vitamin A (e.g., as in a multivitamin).
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 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 known skeletal disease, hypertriglyceridemia, hypercholesterolemia, liver
disease, or other poorly controlled medical conditions.

7. Subject has a medical condition that potentially alters bone metabolism (e.g.,
osteoporosis, thyroid dysfunction, Cushing syndrome), Crohn's disease, or any other
significant concomitant disease 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.

8. Subject is being treated for major depression disorder.

9. Subject with positive serology for hepatitis B surface antigen, hepatitis C, or human
immunodeficiency virus antibody at Screening.

10. Subject with any of the following laboratory values at Screening:

1. Aspartate aminotransferase or alanine aminotransferase >1.5 × upper limit of
normal defined by the laboratory

2. Total bilirubin >1.1mg/dL or, in case of Gilbert's syndrome, total bilirubin
>3mg/dL

3. Hemoglobin <12.5 g/dL for men and <11.5 g/dL for women

4. Platelets <150 × 109/L or >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 a 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 <50 bpm, QRS interval >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 drug 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 related to the sponsor, investigator, or site personnel

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Eastern Health Monash University - Box Hill
Recruitment hospital [2] 0 0
Veracity Clinical Research - Brisbane
Recruitment hospital [3] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [4] 0 0
Premier Specialists Ptd Ltd - Sydney
Recruitment postcode(s) [1] 0 0
- Box Hill
Recruitment postcode(s) [2] 0 0
- Brisbane
Recruitment postcode(s) [3] 0 0
- Parkville
Recruitment postcode(s) [4] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
France
State/province [12] 0 0
Paris
Country [13] 0 0
France
State/province [13] 0 0
Rouen
Country [14] 0 0
France
State/province [14] 0 0
Toulouse
Country [15] 0 0
Spain
State/province [15] 0 0
Barcelona
Country [16] 0 0
Spain
State/province [16] 0 0
Madrid
Country [17] 0 0
Spain
State/province [17] 0 0
Pamplona
Country [18] 0 0
Ukraine
State/province [18] 0 0
Dnipro
Country [19] 0 0
Ukraine
State/province [19] 0 0
Ternopil'
Country [20] 0 0
Ukraine
State/province [20] 0 0
Uzhhorod
Country [21] 0 0
Ukraine
State/province [21] 0 0
Zaporizhzhya

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Mayne Pharma International Pty Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a phase 2 randomized, multi-center, double-blind, vehicle controlled, 12-week,
safety, efficacy, and systemic exposure study followed by a 12-week open-label extension of
trifarotene cream in adults and adolescents with autosomal recessive ichthyosis with lamellar
scale
Trial website
https://clinicaltrials.gov/show/NCT03738800
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Keith A. Choate, MD
Address 0 0
Yale University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Phoevos Hughes, JD
Address 0 0
Country 0 0
Phone 0 0
9193096970
Fax 0 0
Email 0 0
phoevos.hughes@maynepharma.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03738800