Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This is a randomized, double-blind and vehicle-controlled Phase III study to evaluate the
safety and efficacy of topical TMB-001 0.05% ointment for the treatment of CI in subjects
with either the RXLI or ARCI subtypes.
In addition, a subset of preselected centers will recruit subjects in parallel with either
the RXLI or ARCI subtypes for enrollment into an Optional Maximal Use arm for evaluation of
the systemic exposure and safety of topical TMB-001 0.05% ointment for the treatment of CI.
The Phase III Study is designed in three periods:
• Period 1 - Induction (3 weeks): At the beginning of the 3-week Induction Period, eligible
subjects will be randomized (2:1 ratio) to either TMB-001 0.05% once-a-day (QD) or Vehicle QD
treatment, with use of mandatory standardized bland emollient (Cetaphil™) provided by the
Sponsor.
• Period 2 - Treatment (9 weeks): The dosing frequency in the 9-week treatment period will be
increased in each treatment group to TMB-001 0.05% BID or Vehicle BID. Mandatory bland
emollient will be discontinued.
• Period 3 - Maintenance (12 weeks): At Week 12, eligible subjects in the TMB-001 treatment
group will be randomized (1:1 ratio) to an open-label treatment with TMB-001 0.05% BID or
TMB-001 0.05% QD. To be eligible, subjects must have achieved a ≥1-point reduction in IGA
score from Baseline. Subjects with less than a 1-point reduction in IGA score from Baseline
will be discontinued from the study.
Vehicle-treated subjects who achieved <1-point reduction in IGA score from Baseline are
eligible to cross over to the TMB-001 0.05% BID treatment group. Subjects with a ≥1-point
reduction in IGA score from Baseline will be discontinued from the study.
Subjects at the end of the study or subjects discontinued from the study at any time will be
followed-up for additional 2 weeks for AEs.
Phase
Phase 3
Funding Agency/Sponsor
Industry
Disease
Other
Enrollment Eligibility
Inclusion Criteria:
1. Subject is male or female, 6 years of age and older at Visit 2 (Baseline).
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 consent/assent 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. Females must be postmenopausal (defined as amenorrhea greater than 12 consecutive
months in women 50 years of age and older), surgically sterile (hysterectomy,
bilateral salpingectomy, or bilateral oophorectomy), or use 2 acceptable forms of
birth control. WOCBP must have a negative serum pregnancy test at screening and
negative urine pregnancy test (UPT) at Visit 2 (Baseline) (UPTs must have a minimum
sensitivity to detect 25 mIU beta human chorionic gonadotropin [β hCG]/mL). Female
subjects who become sexually active or begin to have relations with a partner during
the study must agree to use 2 forms of birth control for 30 days prior to having
relations and to continue such forms of birth control for the duration of the study.
4. Subject has clinical diagnosis of CI and has a genetic confirmation of either ARCI
(including but not exclusively transglutaminase 1-deficient, ALOX-12B) or RXLI (e.g.,
deletion of steroid sulfatase gene) subtypes of CI. Other genetically confirmed
ARCI-LI mutations can potentially be enrolled as long as the phenotype is consistent
with ARCI and the other inclusion criteria are met, as determined by the Investigator
5. The amount of CI affected skin in the Treatment Area at Baseline will be between a
minimum of 10% and maximum of 90% of the total BSA (1% BSA is approximately equal to
the surface area of the subject's palm and fingers, with the fingers extended yet
grouped together, creating a flat oval-like surface area).
• For the Optional Maximal Use arm: The amount of CI affected skin in the Treatment
Area at Baseline will be between a minimum of 75% and maximum of 90% of the total BSA.
6. Documented history of moderate to severe disease at Screening. Subject's designated
VIIS Assessment Areas at Baseline (not applicable for Optional Maximal Use arm) MUST:
- Include any of the 4 VIIS Assessment Areas that have some CI disease involving:
(a) the upper back from the posterior axillary fold to the other encompassing the
T1-T10, (b) the upper arm (excluding elbows), left or right, (c) the shin/lower
leg (the portion below the proximal aspect of the kneecap), left or right, and
(d) dorsal foot (left or right); AND
- At least 2 of the 4 VIIS Assessment Areas MUST have a scaling score of 3 or more.
7. Subject's IGA score in the Treatment Area at Baseline must be 3 or more.
8. Subject and parent/guardian (if applicable) are willing and able to apply the study
treatment(s) as directed, comply with study instructions, and commit to all follow-up
visits for the duration of the study.
9. Subject, in the Investigator's opinion, is in good general health and free of any
disease state or physical condition that might impair evaluation of the Treatment
Areas or exposes the subject to an unacceptable risk by study participation.
Exclusion Criteria:
1. Subject is pregnant, lactating, or is planning to become pregnant during the study.
2. Subject has inflammatory skin diseases that confound the interpretation of results
(e.g., atopic dermatitis) unrelated to ichthyosis.
3. Subject has genetic abnormality consistent with non-lamellar type or syndromic
ichthyoses (including but not exclusively KRT1, KRT10, KRT2, GJB3, GJB4, CDSN)
4. Subject has previously failed on topical/oral retinoid therapy for treatment of CI,
defined as documented intolerance and or lack of clinical efficacy as determined by
the subject.
5. Subject, in the Treatment Areas, has used: (a) any topical prescription or
over-the-counter (OTC) therapies (except emollients, keratolytics, and topical
steroids - see below), that are intended for, or that in the opinion of the
Investigator, may improve CI within 2 weeks of Visit 2 (Baseline), or (b) keratolytics
or topical corticosteroids within 5 days prior to Visit 2 (Baseline).
6. Subject, in the Treatment Areas, has used TMB-001 in the past or oral isotretinoin in
the past 12 months (not applicable for Optional Maximal Use arm).
7. Subject has used any topical products in the Treatment Areas, including bland
emollients, on Visit 2 (Baseline).
8. Subject has used ultraviolet (UV) treatment within 4 weeks prior to Visit 2
(Baseline).
9. Subject has undergone systemic therapies using vitamin A supplements or St. John's
Wort within 4 weeks prior to Visit 2 (Baseline). Note: Use of a multivitamin including
vitamin A is not exclusionary provided it is taken as directed on the packaging.
10. Subject is immunosuppressed (e.g., human immunodeficiency virus, systemic malignancy,
graft host disease) or receives systemic immunotherapy.
11. Subject is currently taking concomitant immunosuppressive drugs, including systemic
corticosteroids, within 2 weeks of Visit 2 (Baseline).
12. Subject has untreated secondary infections; however, subject may become eligible after
successful treatment of his/her infection(s) at the Investigator's discretion.
13. Subject is currently enrolled in an investigational drug or device study or has used
an investigational drug or investigational device treatment within 30 days or five
half-lives prior to Visit 2 (Baseline).
14. Subject has lesions suspicious for skin cancer (if skin cancer is not ruled out by
biopsy) or untreated skin cancers within the Treatment Areas.
15. Subject has a physical condition or other dermatologic disorder that, in the
Investigator's opinion, might impair evaluation of CI, or that exposes the subject to
unacceptable risk by study participation.
16. Subjects with ALT or AST >2 x Upper Limit of Normal (ULN) and/or creatinine >1.5 x
ULN.
17. Subject is unable to communicate or cooperate with the Investigator due to language
problems, impaired cerebral function, or physical limitations.
18. Subject has a history of drug or alcohol abuse within the past 6 months, or if
suspected 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.
19. Subject has a history of sensitivity to any of the ingredients in the study
treatments.
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