The ASCEND Study: Evaluating TMB-001 in the Treatment of RXLI or ARCI Ichthyosis (NCT05295732) | Clinical Trial Compass
CompletedPhase 3
The ASCEND Study: Evaluating TMB-001 in the Treatment of RXLI or ARCI Ichthyosis
United States153 participantsStarted 2022-06-21
Plain-language 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 congenital ichthyosis (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 (Cetaphilâ„¢) 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 on vehicle 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.
Who can participate
Age range6 Years
SexALL
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Inclusion criteria
✓. Subject is male or female, 6 years of age and older at Visit 2 (Baseline).
✓. 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.
✓. 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.
✓. 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.
What they're measuring
1
Change in Investigator Global Assessment (IGA) Score
. 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).
✓. Documented history of moderate to severe disease at Screening. Subject's designated VIIS Assessment Areas at Baseline (not applicable for Optional Maximal Use arm):
✓. Subject's IGA score in the Treatment Area at Baseline must be 3 or more.
✓. 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.
Exclusion criteria
✕. Subject is pregnant, lactating, or is planning to become pregnant during the study.
✕. Subject has inflammatory skin diseases that confound the interpretation of results (e.g., atopic dermatitis) unrelated to ichthyosis.
✕. Subject has genetic abnormality consistent with non-lamellar type or syndromic ichthyoses (including but not exclusively KRT1, KRT10, KRT2, GJB3, GJB4, CDSN)
✕. 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).
✕. 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).
✕. Subject has used any topical products in the Treatment Areas, including bland emollients, on Visit 2 (Baseline).
✕. Subject has used ultraviolet (UV) treatment within 4 weeks prior to Visit 2 (Baseline).
✕. 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.