The objective of this study is to determine and compare the safety and efficacy of topical 146-9251 cream and vehicle cream applied twice daily for 6 weeks in subjects with moderate to severe ichthyosis vulgaris (IV).

Inclusion Criteria:

1. Subject is a male or female and is at least 12 years old at the time of enrollment.
2. Subject has provided written informed consent/assent. A subject under 18 years of age must provide written informed assent and be accompanied by the parent or legal guardian at the time of assent/consent signing. The parent or legal guardian must provide informed consent for the subject. If a subject becomes 18 years of age during the study, the subject must provide written informed consent at that time to continue study participation.
3. Subject and parent/guardian (if applicable) are willing and able to apply the test article(s) as directed, comply with study instructions, and commit to all follow-up visits for the duration of the study.
4. Subject has a clinical diagnosis of ichthyosis vulgaris involving a minimum of 5% body surface area (BSA). If the subject has IV involving over 40% BSA, the investigator must be able to identify a Treatment Area comprising distinct anatomic units that contains about 40% (excluding the scalp and mucosal areas) as detailed in Section 6.2.
5. Subject has an Investigator's Global Assessment (IGA) score of at least three (3 = moderate) at the Baseline Visit.
6. Subject is in good general health and free of any disease state or physical condition that might impair evaluation of IV or which, in the investigator's opinion, exposes the subject to an unacceptable risk by study participation.
7. Females must be post-menopausal, surgically sterile, or use an effective method of birth control. , Women of childbearing potential (WOCBP) must have with a negative urine pregnancy test (UPT) at the Baseline Visit.

Exclusion Criteria:

• 1. Subject is pregnant, lactating, or is planning to become pregnant during the study.

  2. Subject is currently enrolled in an investigational drug or device study. 3. Subject has used an investigational drug or investigational device treatment within 30 days prior to first application of the test article.

  4. Subject has used any topical therapy, including topical corticosteroids or retinoids, in the Treatment Area within 2 weeks prior to the initiation of treatment. Note: a bland emollient may be used in the Treatment Area up to 3 days prior to the initiation of treatment.

  5. Subject has used systemic corticosteroids within 4 weeks or retinoids within 24 weeks prior to the initiation of treatment.

  6. Subject has stable use of vitamin or herbal supplements for less than 2 weeks prior to the initiation of treatment.

  7. Subject has a history of sensitivity to any of the ingredients in the test articles.

  8. Subject is known to be noncompliant or is unlikely to comply with the requirements of the study protocol (e.g., due to alcoholism, drug dependency, mental incapacity) in the opinion of the investigator.

  9. Subject has a physical condition or other dermatologic disorders (e.g., atopic, seborrheic or contact dermatitis, psoriasis, tinea infections, etc.) which, in the investigator's opinion, might impair evaluation of IV, or which exposes the subject to unacceptable risk by study participation.

Intent to treat (ITT) population defined as subjects who applied at least one dose of the assigned test article.

AEs were collected from study day 1 to end of study (week 6).