Purpose

This is a phase 2 randomized, multi-center, double-blind, vehicle controlled, 90 day, safety, efficacy, and systemic exposure study followed by a 90 day open-label extension of trifarotene cream in adults and adolescents with autosomal recessive ichthyosis with lamellar scale.

Condition

Eligibility

Eligible Ages
Over 12 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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
<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 optional photography has signed a photography ICF.

6. Subject who is participating in the optional PK substudy has signed a PK ICF. Minors,
in the event of their reaching majority during the study, should be capable of giving
consent to take part in the PK substudy.

7. Subject is not of childbearing potential, who is postmenopausal (absence of menstrual
bleeding for 1 year before Baseline, without any other medical reason), or has
documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy. For
individuals with permanent infertility due to an alternate medical cause other than
the above, (e.g., Mullerian agenesis, androgen insensitivity), investigator discretion
should be applied to determining study entry.

OR

- Subject is a woman of childbearing potential (WOCBP), i.e., a female ≥12 years of
age (regardless of whether they have experienced/reported menarche), 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), vaginal ring, or
implanted or injectable hormonal contraceptives with a stable dose for at least 1
month before Baseline; hormonal contraceptives must inhibit ovulation

- intrauterine device (IUD) inserted at least 1 month before Baseline OR Agrees to
abstain from heterosexual intercourse 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.
Abstinence is only acceptable if this is the subject's usual lifestyle. Periodic
abstinence (calendar, symptothermal, postovulation methods), withdrawal (coitus
interruptus), spermicides only, and lactational amenorrhoea method are not
acceptable methods of contraception.

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

Note: Female subjects who are premenstrual at screening should nonetheless follow the
pregnancy testing schedule for WOCBP even if they abstain from sexual intercourse
while in the study and for at least 1 month after the last study drug application.

8. Women of childbearing 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).

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 fasting triglycerides >200 mg/dL or >2.25 mmol/L and/or total cholesterol
>250 mg/dL or >6.5 mmol/L. Subjects whose triglycerides and/or total cholesterol are
within normal limits with a stable dose of lipid-lowering agents for at least 6 months
may be included.

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). Subjects with hypothyroidism who are on a stable dose of thyroid hormone
replacement therapy and whose thyroid-stimulating hormone (TSH) is normal may be
included

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:

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

2. Total bilirubin >1.25 × ULN at Screening. Subjects with known Gilbert's syndrome
may be included with total bilirubin >1.25 × ULN

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 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 has clinically significant
electrocardiogram (ECG) abnormalities, including clinically significant conduction
disorders or significant arrhythmias, or QTcF interval >450 ms.

14. Subject has a known allergy or sensitivity to any of the components of the
investigational products.

15. Subject has been exposed to excessive UV radiations on the treated zones within 1
month before Baseline visit or 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

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
CD5789 Cream 200 µg/g
CD5789 200 µg/g, topical, 50g
  • Drug: 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
Experimental
CD5789 Cream 100 µg/g
CD5789 100 µg/g, topical, 50g
  • Drug: 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
Placebo Comparator
CD5789 Cream Vehicle
CD5789 Cream Vehicle, topical, 50g
  • Drug: CD5789 Cream Vehicle
    A fixed dose (determined at Visit 1) applied topically twice weekly, up to 36 g per dose up to 90% BSA

More Details

Status
Terminated
Sponsor
Mayne Pharma International Pty Ltd

Study Contact

Detailed Description

This is a 2-cohort, multicenter study in subjects with moderate to severe LI. Adults (Cohort A) and adults and adolescents (Cohort B) will be randomized in a double-blind fashion to 1 of 2 doses of active or vehicle and treated twice weekly for 90 days. Subjects who complete the randomized, double-blind portion of the study will be eligible to enter a 90 day, open-label extension study. Approximately 15 adults (≥18 years old) will be randomized into the first cohort of subjects (Cohort A) in a 1:1:1 ratio and treated twice weekly for up to 90 days. If no safety issues are identified, both adults and adolescents (ages 12-17 years, inclusive) will be allowed to enroll in Cohort B. Subjects in Cohort B will be randomized 1:1:1 and treated twice weekly for up to 90 days in the same manner as subjects in Cohort A. All subjects who complete 90 days of double-blind study treatment will be eligible to enroll in a 90 open-label extension. Subjects in the open-label extension will receive active twice weekly for up to 90 days.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.