A Safety, Efficacy and Pharmacokinetics Study of CD11301 for the Treatment of Cutaneous T-Cell Lymphoma (CTCL)

Study Overview
=================
Brief Summary
-----------------
To assess the efficacy, safety and pharmacokinetics in participants treated with CD11301 gel vs. placebo for early stage CTCL (IA, IB, or IIA).

Detailed Description
-----------------
To assess the efficacy and safety of two concentrations (0.03% and 0.06%) of CD11301 gel in the treatment of early stage CTCL (stage IA, IB, or IIA) versus placebo.

Official Title
-----------------
A Randomized, Double-blind, Multi-centre, Placebo-controlled, Parallel-arm Phase 2 Trial to Assess Safety, Efficacy and Pharmacokinetics of CD11301 0.03% and 0.06% Gel in the Treatment of Cutaneous T-Cell Lymphoma (CTCL), Stages IA, IB and IIA

Conditions
-----------------
Cutaneous T Cell Lymphoma

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: CD11301 0.03%
* Drug: CD11301 0.06%


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical Diagnosis of CTCL stage IA, IB, or IIA with biopsy within last 3 months Have BSA involvement corresponding to stages IA, IB or IIA CTCL with at least 3 distinct lesions Exclusion Criteria: CTCL that is stage IIB or great or stage IIA with stage N2 with >5% circulating Sezary cells or CD8+ or large cell transformation or Progressive CTCL History of autoimmune disease Laboratory test values at screening outside of the normal range and judged clinically significant by the investigator Current participation in another clinical trial of a drug or device or past participation within 4 weeks before Baseline or participant is in exclusion period from a previous clinical trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD11301 Gel 0.06%<br>Participants applied 0.06% CD11301 gel (up to 500 mg per dose) topically once daily, 3 to 5 times per week, for cycle 1 and 2 i.e. 24 weeks. | Drug: CD11301 0.06%<br>* Topical Gel<br>|
| Experimental: CD11301 Gel 0.03%<br>Participants applied 0.03% CD11301 gel (up to 500 mg per dose) topically once daily, 3 to 5 times per week, for cycle 1 and 2 i.e. 24 weeks. | Drug: CD11301 0.03%<br>* Topical Gel<br>|
| Experimental: Placebo<br>Participants applied placebo gel during cycle one followed by 0.03% CD11301 gel topically during cycle two once daily, 3 to 5 times per week, for 24 weeks. | Drug: Placebo<br>* Non active ingredients of CD11301<br>Drug: CD11301 0.03%<br>* Topical Gel<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reported Overall Response (Complete and Partial) of Target Treated Lesions Based on Modified Composite Assessment of Index Lesion Severity (mCAILS) Score at Week 12 | Overall response is defined as the number of participants that achieved a complete response (CR) or partial response (PR) as assessed by mCAILS. The mCAILS assessment total was derived from components collected on the case report form (CRF). Target treated lesions (1-5 lesions) were rated in erythema (0-8, where 0=no evidence and 8= very severe), scaling (0-8, where 0=no evidence and 8= very severe), plaque elevation (0-3, where 0=no evidence and 3= marked elevation), and size (scale=0-18, where 0= no measurable area and 18= size of lesion >300 centimeter [cm]^2). These 4 ratings were summed to create subtotals, 1 per lesion. The final mCAILS assessment score was the sum of these subtotals. Total summation Score: 0-50 where higher score indicated higher severity. Complete response is defined as a 100% decrease from baseline i.e. score of '0' on the mCAILS scale. Partial response is defined as at least a 50%, but less than 100%, decrease from baseline. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reported Overall Response (OR) of Target Treated Lesions Based on Modified Severity-Weighted Assessment Tool (mSWAT) Score at Week 12 | OR is defined as the number of participants that achieved a complete response or partial response as assessed by mSWAT. mSWAT composite score involved the direct assessment of the BSA of each type of lesion (palm plus fingers of the participant= approximately 1% BSA) in each of 12 areas (Head, Neck, Anterior trunk, Arms, Forearms, Hands, Posterior trunk, Buttocks, Thighs, Legs, Feet, Groin) of the body, multiplying the sum of the BSA of each lesion type by a weighting factor (patch = 1, plaque = 2, and tumor = 3 or 4) and generating a sum of the subtotals of each lesion subtype. mSWAT score (0=no lesions; 400= lesions covering all areas). Complete response is defined as a 100% decrease from baseline. Partial response is defined as at least a 50%, but less than 100%, decrease from baseline, and with a tumor subscore of zero (no tumor). | Week 12 | 
| Time to Participant's First Overall Response (Complete or Partial) of the Target Treated Lesions Based on the mCAILS Score | Time to overall response (CR or PR) is the number of days from the start of drug application to the first documentation of objective response assessed by mCAILS Score. The 25th, 50th, and 75th percentiles were presented along with 95% confidence intervals using the log-log transformation. The mCAILS assessment total was derived from components collected on the case report form (CRF). Target treated lesions (1-5 lesions) were rated in erythema (0-8, where 0=no evidence and 8= very severe), scaling (0-8, where 0=no evidence and 8= very severe), plaque elevation (0-3, where 0=no evidence and 3= marked elevation), and size (scale=0-18, where 0= no measurable area and 18= size of lesion >300 centimeter [cm]^2). These 4 ratings were summed to create subtotals, 1 per lesion. The final mCAILS assessment score was the sum of these subtotals. Total summation Score: 0-50 where higher score indicated higher severity. | Up to Week 36 | 
| Duration of Overall Response (Complete Response or Partial Response) Based on mCAILS Score | The duration of overall response (complete or partial) of the target treated lesions based on the mCAILS score was calculated in days as: (date of first non-response after responding) - (date of response) + 1. The mCAILS assessment total was derived from components collected on the case report form (CRF). Target treated lesions (1-5 lesions) were rated in erythema (0-8, where 0=no evidence and 8= very severe), scaling (0-8, where 0=no evidence and 8= very severe), plaque elevation (0-3, where 0=no evidence and 3= marked elevation), and size (scale=0-18, where 0= no measurable area and 18= size of lesion >300 centimeter [cm]^2). These 4 ratings were summed to create subtotals, 1 per lesion. The final mCAILS assessment score was the sum of these subtotals. Total summation Score: 0-50 where higher score indicated higher severity. | Up to Week 36 | 
| Time to Progressive Disease Using mSWAT | Progressive disease is defined as ≥ 25% increase in skin disease from baseline, or loss of response: in those with CR or PR, increase of skin score of greater than the sum of nadir plus 50% baseline score, Nadir is defined as the lowest skin score (best response). | Up to Week 36 | 
| Change From Baseline in Skindex-29 Survey Results at Week 12, 24 and 36 | Participants answered 30 questions as part of the Skindex-29 survey. A composite score and 3 sub scores were calculated from the results. Item 18 of the survey was not used in any scoring. First, answers to each item were given a numeric value: Never = 0; Rarely = 25; Sometimes = 50; Often = 75; All the time = 100. The items used to calculate each subscore were: Emotions: 3, 6, 9, 12, 13, 15, 21, 23, 26, and 28 (10 items), Symptoms: 1, 7, 10, 16, 19, 24, and 27 (7 items), Functioning: 2, 4, 5, 8, 11, 14, 17, 20, 22, 25, 29, and 30 (12 items). The composite score is the average of the 3 sub scores ranging from 0 (no effect)-100 (maximum effect), higher score corresponds to lower quality of life. | Week 12, 24 and Follow up (Week 36) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
T-Cell, Lymphoma, Cutaneous, CTCL