A Safety, Efficacy and Systemic Exposure Study of CD5789 Cream in Adults and Adolescents With Lamellar Ichthyosis
Condition: Lamellar Ichthyosis
MeSH terms: Ichthyosis; Ichthyosis, Lamellar
Intervention: CD5789 Cream 200 µg/g; CD5789 Cream 100 µg/g; CD5789 Cream Vehicle
Intervention description: A fixed dose (determined at Visit 1) of 200 µg/g applied topically twice weekly to up to 90% BSA; A fixed dose (determined at Visit 1) of 100 µg/g applied topically twice weekly to up to 90% BSA; A fixed dose (determined at Visit 1) applied topically twice weekly, up to 36 g per dose up to 90% BSA
Intervention MeSH terms: Trifarotene
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 65.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility 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.