A Phase 2 Study With CC-220 in Skin Sarcoidosis

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

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

Study Overview

• Status: Withdrawn
• Conditions: Sarcoidosis
• Intervention / Treatment: Drug: Placebo; Drug: CC-220 0.3 mg Daily; Drug: CC-220 0.6mg Daily

Detailed Description

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

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Yufang Lu, MD, PhD, Celgene Corporation

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2014
• Primary Completion (Anticipated): June 30, 2017
• Study Completion (Anticipated): June 30, 2017

Study Registration Dates

• First Submitted: July 15, 2014
• First Submitted That Met QC Criteria: July 15, 2014
• First Posted (Estimate): July 16, 2014

Study Record Updates

• Last Update Posted (Actual): November 12, 2019
• Last Update Submitted That Met QC Criteria: November 7, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Sarcoidosis; Skin Sarcoidosis; Chronic Cutaneous Sarcoidosis; Cutaneous Sarcoidosis
• Additional Relevant MeSH Terms: Lymphoproliferative Disorders; Lymphatic Diseases; Sarcoidosis
• Other Study ID Numbers: CC-220-SAR-001; 2014-001065-27 (EudraCT Number)