A Safety, Efficacy and Systemic Exposure Study of CD5789 Cream in Adults and Adolescents With Lamellar Ichthyosis

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.