Safety and Efficacy of CD10367 in Psoriasis Vulgaris

Phase 2

Completed

• Conditions: Psoriasis Vulgaris
• Interventions: Drug: CD10367 1% Solution - Non-desquamated zone; Drug: CD10367 3% Solution - Non-desquamated zone; Drug: CD10367 solution placebo - Non-desquamated zone; Drug: Betneval ointment - Non-desquamated zone; Drug: CD10367 3% Solution - Desquamated zone; Drug: CD10367 solution placebo - Desquamated zone

• Registration Number: NCT03025282
• Lead Sponsor: Galderma R&D

Brief Summary

This is an exploratory, single-centre, investigator blinded, randomized, controlled, intra-individual study, involving subjects with psoriasis vulgaris.

The objective is to evaluate, in a modified Dumas-Scholtz psoriasis mini-zone test, the safety and efficacy of CD10367 solution at 1% and 3% after a 3-week treatment period of once daily application.

Detailed Description

Study drugs will be applied in each subject once daily, 5 days a week during the first 2 weeks and for 4 days the third week on 6 mini-zones located on at least 2 psoriatic plaques as described below:

* on 2 mini-zones pretreated by a keratolytic product, will be tested:

* CD10367 3% solution

* CD10367 solution placebo

* on 4 mini-zones non-pretreated, will be tested:

* CD10367 3% solution

* CD10367 1% solution

* CD10367 solution placebo

* Betneval 0.1% ointment

Study Timeline

• Study Start: 2016-11-03
• Study First Submitted: 2017-01-17
• Study First Submitted QC: 2017-01-17
• Study First Posted: 2017-01-19
• Primary Completion: 2017-03-24
• Study Completion: 2017-03-24
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-04
• Last Update Posted: 2017-04-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Adult male or female aged at least 18 and up to 70 years old inclusive at screening visit.
2. Female of non childbearing potential (postmenopausal [absence of menstrual bleeding for 1 year prior to screening, without any other medical reason], hysterectomy or bilateral oophorectomy).
3. Subject has a skin phototype I to IV on Fitzpatrick's scale. (Screening visit).
4. The subject has a clinical diagnosis of stable plaque psoriasis, defined as no flare during the month before Screening visit and no change between Screening visit and Baseline visit, of mild to moderate severity. (Screening visit and Baseline Visit).
5. The subject presents with at least six eligible mini-zones, on at least two psoriasis plaques (Screening visit and verified also at Baseline Visit) with specific severity grades,
6. Subject agrees not to wear his/her contact lenses from the Baseline visit till the D19 visit, (Screening visit)

Exclusion Criteria

1. The subject presents guttate, erythrodermic, exfoliative, inverse, pustular, palmo plantar, infected or ulcerated psoriasis (Screening visit).
2. The subject has any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with the interpretation of the clinical trial results, and/or put the subject at significant risk (according to Investigator's judgment) if he/she participates in the clinical trial (e.g. history of on-going gastric or duodenal ulcer, clinically significant lung disease, etc.) (Screening visit).
3. The subject has known or suspected allergies or sensitivities to any components of the study drugs or of the keratolytic product (see Investigator's Brochure/Product label). (Screening visit).
4. The subject has known history of adverse drug reaction or hypersensitivity to a product with the same mode of action
5. The subject has any abnormal clinically significant findings according to the ophthalmologist, at the ophthalmological exam at Screening visit,
6. The subject presents any abnormal laboratory tests judged clinically significant by the investigator (blood samplings and urinalysis done at Screening visit),
7. The subject has QTc interval >450msec or any abnormal ECG value considered as clinically significant by the cardiologist (Screening visit).
8. The subject has received, applied or taken some specified treatments within the specified time frame prior to the Baseline visit.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CD10367 1% Solution - Non-desquamated zone	CD10367 1% Solution - Non-desquamated zone	-
CD10367 3% Solution - Non-desquamated zone	CD10367 3% Solution - Non-desquamated zone	-
CD10367 solution placebo - Non-desquamated zone	CD10367 solution placebo - Non-desquamated zone	CD10367 solution placebo serves as negative control.
Betneval ointment - Non-desquamated zone	Betneval ointment - Non-desquamated zone	This comparator containing Betamethasone valerate 0.1% serves as positive control.
CD10367 3% Solution - Desquamated zone	CD10367 3% Solution - Desquamated zone	-
CD10367 solution placebo - Desquamated zone	CD10367 solution placebo - Desquamated zone	-

Primary Outcome Measures

Name	Time	Method
Area Under the Curve (AUC) of Total Sum Score (Sum of Erythema, Scaling and Induration Scores)	Day 1 to Day 19	The TSS is the sum of the individual clinical scores of erythema, scaling and induration determined on a mini-zone. Each score was evaluated by the Investigator on all mini-zones using a 5-point scale (0: none; 1: mild; 2: moderate; 3: severe; 4: very severe) and were summed to obtain the Total Sum Score (TSS). Maximum total score was 12 (very severe); minimum total score was 0 (None). The mean AUC of TSSs were calculated for each intervention for all participants.

Secondary Outcome Measures

Name	Time	Method
Area Under the Curve (AUC) of Individual Clinical Scores	Day 1 to Day 19	Each mini zone was evaluated by recording individual clinical scores (items: erythema, scaling, induration) for each participant using 5-point scale for each item and score ranged from 0(none), 1(mild), 2(moderate), 3(severe) and 4(very severe). Erythema: 0=No detectable erythema,1=Slight pinkness present, 2=Definite redness, easily recognized, 3=Intense redness, 4=Very intense redness; Scaling: 0=No shedding, 1=Barely perceptible shedding, noticeable only on light scratching or rubbing, 2=Obvious but not profuse shedding, 3=Heavy scale production, 4=Very thick scales; Induration: 0=Normal skin thickness/No elevation of skin, 1=Barely perceptible elevation (by touching) of the psoriasis plaques, 2=Obvious elevation above normal skin level/moderate thickening, 3=Definite thick elevation above normal skin level, 4=Very thick elevation. Higher score indicated worst conditions. The mean AUC for each intervention was calculated for each participant.
Total Sum Score (TSS) of Individual Clinical Scores	Day 1, Day 4, Day 8, Day 11, Day 15 and Day 19	The TSS was the sum of the individual clinical scores of erythema, scaling and induration determined on a mini-zone. Each score was evaluated by the Investigator on all mini-zones using a 5-point scale (0: none; 1: mild; 2: moderate; 3: severe; 4: very severe) and were summed to obtain the Total Sum Score (TSS). where maximum total score was 12 (worst condition) and minimum total score was 0 (no symptoms).
Percent Change in Total Sum Score (TSS)	Day 1, Day 4, Day 8, Day 11, Day 15 and Day 19	The TSS was the sum of the individual clinical scores of erythema, scaling and induration determined on a mini-zone. Each score was evaluated by the Investigator on all mini-zones using a 5-point scale (0: none; 1: mild; 2: moderate; 3: severe; 4: very severe) and were summed to obtain the Total Sum Score (TSS). where maximum score was 12 (worst condition) and minimum score was 0 (no symptoms). The TSS percentage change from Day 1 at each visit and erythema, scaling and induration scores and their changes from Day 1 at each visit were evaluated by visit and by treatment received.
Erythema, Scaling and Induration Scores at Each Visit	Day 1, Day 4, Day 8, Day 11, Day 15 and Day 19	Status of psoriasis for each mini zone was evaluated by recording individual clinical scores (items: erythema, scaling, induration) using 5-point scale for each item and score ranged from 0(none), 1(mild), 2(moderate), 3(severe) and 4(very severe). Erythema: 0=No detectable erythema,1=Slight pinkness present, 2=Definite redness, easily recognized, 3=Intense redness, 4=Very intense redness; Scaling: 0=No shedding, 1=Barely perceptible shedding, noticeable only on light scratching or rubbing, 2=Obvious but not profuse shedding, 3=Heavy scale production, 4=Very thick scales; Induration: 0=Normal skin thickness/No elevation of skin, 1=Barely perceptible elevation (by touching) of the psoriasis plaques, 2=Obvious elevation above normal skin level/moderate thickening, 3=Definite thick elevation above normal skin level, 4=Very thick elevation. Higher score indicated worst conditions.
Percent Changes of Erythema, Scaling and Induration From Day 1 to Day 19	Day 1, Day 4, Day 8, Day 11, Day 15, Day 19	Status of psoriasis for each mini zone was evaluated by recording individual clinical scores (items: erythema, scaling, induration) using 5-point scale for each item and score ranged from 0(none), 1(mild), 2(moderate), 3(severe) and 4(very severe). Erythema: 0=No detectable erythema,1=Slight pinkness present, 2=Definite redness, easily recognized, 3=Intense redness, 4=Very intense redness; Scaling: 0=No shedding, 1=Barely perceptible shedding, noticeable only on light scratching or rubbing, 2=Obvious but not profuse shedding, 3=Heavy scale production, 4=Very thick scales; Induration: 0=Normal skin thickness/No elevation of skin, 1=Barely perceptible elevation (by touching) of the psoriasis plaques, 2=Obvious elevation above normal skin level/moderate thickening, 3=Definite thick elevation above normal skin level, 4=Very thick elevation. Higher score indicated worst conditions.
Number of Participants With Success Rate at Each Visit	Day 4, Day 8, Day 11, Day 15 and Day 19	Success rate was defined as a clearing score of 0 or 1, at each evaluation visit (Day 4, Day 8, Day 11, Day 15 and Day 19). The clearing score was ranged from 0 to 2, where scores were indicated as follows: 0=complete clearing (no scaling and no infiltration even on palpation. Post inflammatory hypo- or hyperpigmentation might be present, 1=almost clear (Residual erythema with some induration/infiltration \[not clinically visible but palpable\] without scaling, or residual erythema and residual scaling with no infiltration, 2=unchanged (unchanged or less than almost clear). Higher score indicated less success in clearing condition (worse outcome).
Time to First Success	Day 1 to Day 19	The time to first success was defined as 0=no Success at any day, 1=success at Day 19 and not before, 2=success at Day 15 and not before, 3=success at Day 11 and not before, where lower score indicated less success in clearing condition (worse outcome).

Trial Locations

Locations (1)

Galderma Investigational Site; 🇫🇷 Nice, France