A Phase 2 Study With CC-220 in Skin Sarcoidosis

Phase 2

Withdrawn

• Conditions: Sarcoidosis
• Interventions: Drug: CC-220 0.3 mg Daily; Drug: Placebo; Drug: CC-220 0.6mg Daily

• Registration Number: NCT02192489
• Lead Sponsor: Celgene

Brief Summary

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

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 Timeline

• Study First Submitted: 2014-07-15
• Study First Submitted QC: 2014-07-15
• Study First Posted: 2014-07-16
• Study Start: 2014-11-01
• Primary Completion: 2017-06-30
• Study Completion: 2017-06-30
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-07
• Last Update Posted: 2019-11-12

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CC-220 0.3mg	CC-220 0.3 mg Daily	CC-220 0.3 mg capsules by mouth (PO) daily for 12 weeks
Placebo	Placebo	Identically matching placebo PO daily for 12 weeks
CC-220 0.6mg	CC-220 0.6mg Daily	CC-220 0.6mg capsules by PO daily for 12 weeks

Primary Outcome Measures

Name	Time	Method
Number of participants with adverse events (AEs)	Up to 12 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics- Maximum Plasma Concentration (Cmax) of CC-220 After Single and Multiple Doses	Day 1 and Day 29 at predose, 1, 2, 3, 4, 6, 8, and 24 hours post-dose	Maximum observed plasma concentration after a single dose on Day 1 or multiple doses on Day 29).
Improvement in lesion induration	Week 12	Change from baseline in lesion induration via dermascope compared to Week 12
Pharmacokinetics - Apparent Total Clearance of CC-220 (CL/F) After Single and Multiple Doses	Day 1 and Day 29 at predose, 1, 2, 3, 4, 6, 8, and 24 hours post-dose	The apparent total clearance after a single dose on Day 1 and multiple doses Day 29, calculated as Dose/AUC0-inf
Pharmacokinetics - Time to Maximum Plasma Concentration (Tmax) After Single and Multiple Doses	Day 1 and Day 29 at predose, 1, 2, 3, 4, 6, 8, and 24 hours post-dose	The time to first maximum observed plasma concentration of CC-220 after a single dose (Day 1) or multiple doses (Day 29).
Improvement in sarcoidosis disease markers	Weeks 4, 8, 12	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.
Pharmacokinetics - Area Under the Plasma Concentration-time Curve From Time Zero to Infinity After Single and Multiple Doses (AUC0-inf)	Day 1 and Day 29 at predose, 1, 2, 3, 4, 6, 8, and 24 hours post-dose	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.
Pharmacokinetics - Terminal Phase Half-life (t1/2) After Single and Multiple Doses	Day 1 and Day 29 at predose, 1, 2, 3, 4, 6, 8, and 24 hours post-dose	Terminal phase elimination half-life (t1/2) after a single dose on day 1 and multiple doses on Day 29
Improvement in modified Sarcoidosis Activity and Severity Index	Week 4, 8 and 12	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
Pharmacokinetics - Apparent Volume of Distribution (Vz/f) After Single and Multiple Doses	Day 1 and Day 29 at predose, 1, 2, 3, 4, 6, 8, and 24 hours post-dose	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
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)	Day 1 and Day 29 at predose, 1, 2, 3, 4, 6, 8, and 24 hours post-dose	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).