Sarcoidosis
Conditions
Keywords
Chronic Cutaneous Sarcoidosis, Cutaneous Sarcoidosis, Skin Sarcoidosis, Sarcoidosis
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
Interventions
DRUGCC-220 0.3 mg Daily
DRUGCC-220 0.6mg Daily
DRUGPlacebo
Sponsors
Celgene
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Improvement in lesion induration | Week 12 | Change from baseline in lesion induration via dermascope compared to Week 12 |
| 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- 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). |
| 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). |
| 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 - 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 |
| 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 - 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). |
| 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. |
Outcome results
None listed