A Phase 2 Study With CC-220 in Skin Sarcoidosis

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of oral CC-220 in adult subjects with chronic cutaneous sarcoidosis.

Detailed Description
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This is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled, sequential, dose-ascending, safety and tolerability study in subjects with chronic cutaneous sarcoidosis. Two dose cohorts of CC-220 (Cohort 1: 0.3 mg by mouth (PO) every day (QD) or matching placebo and Cohort 2: 0.6 mg PO QD or matching placebo) will be evaluated using a sequential, dose-ascending design

Official Title
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A Phase 2A, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Sequential, Dose-Ascending Study Of CC-220 In Subjects With Chronic Cutaneous Sarcoidosis

Conditions
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Sarcoidosis

Intervention / Treatment
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* Drug: CC-220 0.3 mg Daily
* Drug: CC-220 0.6mg Daily
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females aged ≥ 18 years at the time of consent. Have chronic cutaneous sacrcoidosis (CCS) prior to consent Have active cutaneous sarcoidosis lesion(s) at screening Forced vital capacity of ≥ 45% of predicted normal value at screening. Estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/min. Females of childbearing potential must have negative pregnancy tests prior to starting study therapy and agree to either commit to true abstinence or use effective contraception. Male subjects must practice true abstinence or agree to use a condom even if he has undergone a successful vasectomy Exclusion Criteria: Positive tuberculosis test at screening. History of inadequately treated tuberculosis History of Human Immunodeficiency Virus (HIV) and/or Common Variable Immunodeficiency Disease. History of alcohol or drug abuse History or current peripheral neuropathy Current uveitis or any other clinically significant ophthalmological finding Currently require therapy for precapillary pulmonary hypertension.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CC-220 0.3mg<br>CC-220 0.3 mg capsules by mouth (PO) daily for 12 weeks | Drug: CC-220 0.3 mg Daily<br> <br> |
| Experimental: CC-220 0.6mg<br>CC-220 0.6mg capsules by PO daily for 12 weeks | Drug: CC-220 0.6mg Daily<br> <br> |
| Placebo Comparator: Placebo<br>Identically matching placebo PO daily for 12 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) | An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health. | Up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in modified Sarcoidosis Activity and Severity Index | Proportion of subjects who achieve a ≥ 1-point change in the index lesion as measured by the cutaneous sarcoidosis outcome instrument (modified Sarcoidosis Activity and Severity Index) as compared to baseline | Week 4, 8 and 12 | 
| Improvement in lesion induration | Change from baseline in lesion induration via dermascope compared to Week 12 | Week 12 | 
| Improvement in sarcoidosis disease markers | Change from baseline in sarcoidosis disease markers: serum angiotensin converting enzyme (ACE), Immunoglobulin G (IgG) levels, 25-hydroxy vitamin D (25-OH-vit D), and 1,25-dihydroxy vitamin D (1,25-vit D) as compared to Weeks 4, 8 and 12. | Weeks 4, 8, 12 | 
| Pharmacokinetics- Maximum Plasma Concentration (Cmax) of CC-220 After Single and Multiple Doses | Maximum observed plasma concentration after a single dose on Day 1 or multiple doses on Day 29). | Day 1 and Day 29 at predose, 1, 2, 3, 4, 6, 8, and 24 hours post-dose | 
| Pharmacokinetics - Area Under the Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Time Point After Single and Multiple Doses (AUC 0-t) | Area under the plasma concentration time-curve from time 0 to the last quantifiable concentration at time t following a single dose (day 1) and multiple doses (Day 29) determined using the trapezoidal method (non-compartmental analysis). | Day 1 and Day 29 at predose, 1, 2, 3, 4, 6, 8, and 24 hours post-dose | 
| Pharmacokinetics - Area Under the Plasma Concentration-time Curve From Time Zero to Infinity After Single and Multiple Doses (AUC0-inf) | The area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) for CC-220 after a single dose on day 1 and multiple doses on Day 29, calculated by the linear trapezoidal rule and extrapolated to infinity. | Day 1 and Day 29 at predose, 1, 2, 3, 4, 6, 8, and 24 hours post-dose | 
| Pharmacokinetics - Terminal Phase Half-life (t1/2) After Single and Multiple Doses | Terminal phase elimination half-life (t1/2) after a single dose on day 1 and multiple doses on Day 29 | Day 1 and Day 29 at predose, 1, 2, 3, 4, 6, 8, and 24 hours post-dose | 
| Pharmacokinetics - Apparent Volume of Distribution (Vz/f) After Single and Multiple Doses | Apparent volume of distribution after a single dose on day 1 and multiple doses on Day 29, based on the terminal phase after a orally administration | Day 1 and Day 29 at predose, 1, 2, 3, 4, 6, 8, and 24 hours post-dose | 
| Pharmacokinetics - Apparent Total Clearance of CC-220 (CL/F) After Single and Multiple Doses | The apparent total clearance after a single dose on Day 1 and multiple doses Day 29, calculated as Dose/AUC0-inf | Day 1 and Day 29 at predose, 1, 2, 3, 4, 6, 8, and 24 hours post-dose | 
| Pharmacokinetics - Time to Maximum Plasma Concentration (Tmax) After Single and Multiple Doses | The time to first maximum observed plasma concentration of CC-220 after a single dose (Day 1) or multiple doses (Day 29). | Day 1 and Day 29 at predose, 1, 2, 3, 4, 6, 8, and 24 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Cutaneous Sarcoidosis, Cutaneous Sarcoidosis, Skin Sarcoidosis, Sarcoidosis