A Safety, Efficacy and Systemic Exposure Study of CD5789 Cream in Adults and Adolescents With Lamellar Ichthyosis
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|ClinicalTrials.gov Identifier: NCT03738800|
Recruitment Status : Recruiting
First Posted : November 13, 2018
Last Update Posted : March 17, 2020
|Condition or disease||Intervention/treatment||Phase|
|Lamellar Ichthyosis||Drug: CD5789 Cream 200 µg/g Drug: CD5789 Cream 100 µg/g Drug: CD5789 Cream Vehicle||Phase 2|
This is a 2-cohort, multicenter study in subjects with moderate to severe LI. Adults (Cohort A) and adults and adolescents (Cohort B) will be randomized in a double-blind fashion to 1 of 2 doses of active or vehicle and treated twice weekly for 12 weeks. Subjects who complete the randomized, double-blind portion of the study will be eligible to enter a 12 week, open-label extension study.
Approximately 15 adults (≥18 years old) will be randomized into the first cohort of subjects (Cohort A) in a 1:1:1 ratio and treated twice weekly for up to 12 weeks. If no safety issues are identified, both adults and adolescents (ages 12-17 years, inclusive) will be allowed to enroll in Cohort B. Subjects in Cohort B will be randomized 1:1:1 and treated twice weekly for up to 12 weeks in the same manner as subjects in Cohort A.
All subjects who complete 12 weeks of double-blind study treatment will be eligible to enroll in a 12-week open-label extension. Subjects in the open-label extension will receive active twice weekly for up to 12 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Phase 2 Randomized, Multicenter, Doubleblind, Vehicle Controlled, 12 Week, Safety, Efficacy & Systemic Exposure Study Followed by a 12 Week Open-label Extension of CD5789 in Adults and Adolescents With Autosomal Recessive Ichthyosis With Lamellar Scale|
|Actual Study Start Date :||May 1, 2019|
|Estimated Primary Completion Date :||September 10, 2020|
|Estimated Study Completion Date :||December 4, 2020|
Experimental: CD5789 Cream 200 µg/g
CD5789 200 µg/g, topical, 50g
Drug: CD5789 Cream 200 µg/g
A fixed dose (determined at Visit 1) of 200 µg/g applied topically twice weekly to up to 90% BSA
Experimental: CD5789 Cream 100 µg/g
CD5789 100 µg/g, topical, 50g
Drug: CD5789 Cream 100 µg/g
A fixed dose (determined at Visit 1) of 100 µg/g applied topically twice weekly to up to 90% BSA
Placebo Comparator: CD5789 Cream Vehicle
CD5789 Cream Vehicle, topical, 50g
Drug: CD5789 Cream Vehicle
A fixed dose (determined at Visit 1) applied topically twice weekly, up to 36 g per dose up to 90% BSA
- The number of subjects in each treatment group who experience successful resolution of LI. [ Time Frame: 12 weeks ]The number of subjects in each treatment group who experience successful resolution of LI where "success" is defined as clear/almost clear overall and at least a 50% reduction from Baseline at Week 12/end-of-treatment (EOT) in the Double-blind Period on the overall 16-point VIIS for scaling (i.e., 0-4 points on each of the 4 body areas: chest/abdomen, back, arms, and legs).
- The difference in mean scores using Individual score for roughness [ Time Frame: 12 weeks ]
The amount of roughness of the skin will be measured on a 5-point scale. 0 (Clear) Smooth skin
- (Almost Clear) Hardly palpably roughness
- (Mild) Mild roughness (fine sand paper-like)
- (Moderate) Moderate, coarse roughness (coarse sand paper-like)
- (Severe) Very coarse skin (broken cornflakes-like)
- The difference in mean scores using Palm Sole Assessment [ Time Frame: 12 weeks ]
Thickening of the skin on the palms and soles will be measured on a 5-point scale:
0 (Clear) No thickening, no roughness, no fissure
- (Almost Clear) Only slight thickening, minimal to no roughness, no fissures
- (Mild) Some thickening, mild roughness on palpation, few fissures may be present
- (Moderate) Substantial and diffuse thickening, coarse roughness on palpation may be present, fissures may be present
- (Severe) Very thickened and rough skin, numerous fissures
- The difference in proportion of subjects with presence of fissures between the active and vehicle groups [ Time Frame: 12 weeks ]Fissuring will be assessed by recording the presence or absence of fissures, the number of fissures present, and the pain associated with each fissure. The subject will assess pain associated with fissures as ranging from 0-3 (none, mild, moderate, severe) at week 12 between the active trifarotene cream HE1 and vehicle groups
- Quality of life measurement per Dermatology Life Quality Index (DLQI) [ Time Frame: 12 weeks ]
The DLQI, or the Dermatology Quality of Life Index, is a dermatology-specific Quality of Life instrument. It is a simple 10-question validated questionnaire with 6 domains (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment); higher scores indicate poorer quality of life. Responses collected are on a scale of 0-3 depending on the question relevance to the subject.
Response (Score) Very much (scored 3) A lot (scored 2) A little (scored 1) Not at all (scored 0) Not relevant (scored 0) A minimum score of 0 and maximum score of 30 is obtained by summing the score of each question. The higher the score, the more quality of life is impaired.
0-1 = no effect at all on patient's life 2-5 = small effect on patient's life 6-10 = moderate effect on patient's life 11-20 = very large effect on patient's life 21-30 = extremely large effect on patient's life
- 5-point Visual Index for Ichthyosis Severity (VIIS) [ Time Frame: 12 weeks ]
The amount of scaling will be measured on a 5-point scale. 0 (Clear) No scaling
- (Almost Clear) Very fine, non-coalescent scales
- (Mild) Small and thin, non-coalescent scales
- (Moderate) Large and rather thick scales starting to coalesce
- (Severe) Very large, adherent, coalescent and very thick scales
- The difference in mean ectropion scores between the active and vehicle groups [ Time Frame: 24 weeks ]
The Ectropion Severity Score (ESS), is a proven system to be reliable and sensitive to the presence of ectropion and has a maximum score of 8 points (0-8). A higher score indicates a worse ectropion. The score takes the severity of ectropion in terms of lateral and medial apposition, scleral show, conjunctival show, and roundness of the eye into account and gives an indication of the functional aspects involved in ectropion by scoring redness, excess tear film, and the position of the lacrimal punctum A point scale of 0=Nonaffected, 0.5=Emerging, 1= Affected is assigned to 8 observations.
- Lateral apposition
- Medial apposition
- Sceral show
- Conjunctival show
- Excess team film
- Redness of the eye
- Round canthus
- Punctum lacrimale
- Quality of life measurement per EQ-5D-5L [ Time Frame: 24 weeks ]
The EQ-5D is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life used in a wide range of health conditions and treatments. The EQ-5D consists of a descriptive system and the EQ visual analog scale (VAS). Descriptive system of health-related quality of life states consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which can take 1 of 5 responses.
- no problem
- slight problems
- moderate problems
- severe problems
- extreme problems It should be noted that the numerals 1-5 have no arithmetic properties and should not be used as a cardinal score. The EQ VAS records the respondent's self-rated health on a 20 cm vertical, visual analogue scale with endpoints labelled 100-'the best health you can imagine' and 0-'the worst health you can imagine'. This information can be used as a quantitative measure of health as judged by the individual respondents.
- Incidents of adverse events [ Time Frame: 24 weeks ]The number of subjects with AEs will be collected for each treatment group
- Measurement of local tolerability [ Time Frame: 24 weeks ]Local tolerability will be assessed on a 0-3 scale (none, mild, moderate, severe).
- Clinical Laboratory Evaluations [ Time Frame: 24 weeks ]The number of subjects with clinical laboratory values categorized as below (vital signs, 12 lead electrocardiogram, Physical Exam), within, or above normal ranges will be evaluated (changes from baseline for each clinical laboratory parameter by treatment group and by study visit).
- Measurement of vital signs [ Time Frame: 24 weeks ]Blood pressure (systolic blood pressure [SBP], diastolic blood pressure [DBP] and pulse will be measured. Measurement of actual values and changes from baseline will be calculated. Vital signs The number of subjects with vital signs values categorized as below, within, or above normal ranges (change from baseline for each parameter by period, by treatment group and by study visit).
- Measurement of 12-lead ECG Readings [ Time Frame: 24 weeks ]The number of subjects with normal and abnormal ECG findings will be measured for each treatment group at each time point for QT and the QT interval corrected for heart rate (QTc) calculated using Fridericia's QT correction methods.
- Physical examination findings [ Time Frame: 24 weeks ]The number of subjects with normal and abnormal findings in the complete physical examination for each treatment group. This is a limited physical examination to include HEENT, cardiorespiratory, abdomen, and range of motion.
- Measurement of area under the plasma concentration versus time curve (AUC) [ Time Frame: 24 weeks ]Measurement of the extent of absorption using estimates of the area-under-the-curve (AUC).
- Measurement of peak plasma concentration (Cmax) [ Time Frame: 24 weeks ]Measurement of therate-of-absorption using the maximum concentration (Cmax) and the time of Cmax (Tmax).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03738800
|Contact: Phoevos Hughes, JDfirstname.lastname@example.org|
|Contact: Alicia Altonemail@example.com|
|Principal Investigator:||Keith A. Choate, MD||Yale University|