Clinical trial NCT02317627
Conditions: Psoriasis Vulgaris
Sponsor: Kadmon Corporation, LLC
Start date: 2014-12-01; Completion date: 2016-03-01
Enrollment: 38 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study was performed to evaluate the safety, tolerability, activity, pharmacokinetics (PK), and daily dose regimen of KD025 administered orally (PO) for 12 weeks to subjects with psoriasis vulgaris who failed at least one line of systemic therapy.

Detailed description:
Study KD025-206 was a phase 2, open-label, dose-finding, safety, tolerability, activity, and PK study of KD025 in subjects with psoriasis who had failed at least 1 line of systemic therapy or phototherapy.

Subjects received KD025 PO for 12 weeks. Planned enrollment was 36 subjects in 3 cohorts, 12 subjects per cohort:

* Cohort 1 (12 subjects): KD025 400 mg once daily (QD) PO for 12 weeks
* Cohort 2 (12 subjects): KD025 200 mg PO twice daily (BID) for 12 weeks
* Cohort 3 (12 subjects): KD025 400 mg BID PO for 12 weeks

Subjects were initially enrolled simultaneously in Cohort 1 and Cohort 2 according to a randomization schedule, with safety reviewed before any subjects. If safety guidelines were met, Cohort 3 was added to explore the efficacy and safety of KD025 at a dose of 400 mg PO BID.

Subjects underwent safety evaluations: medical history evaluations; physical examinations (PEs); vital sign measurements; weight measurements; adverse event (AE) assessments; concomitant medication assessments; blood sample collection for hematology, chemistry, and coagulation; lipid panel; thyroid-stimulating hormone; measurements of antinuclear antibody; anti-double-stranded deoxyribonucleic acid; Complement C; antiphospholipid antibody; liver ultrasound (US); pregnancy testing for females of childbearing potential; PK sampling (subset of subjects only); urinalysis; and electrocardiogram (ECG).

Subjects underwent efficacy evaluations: Psoriasis Area and Severity Index (PASI) scoring; Physicians Global Assessment (PGA) scoring; and Dermatologic Life Quality Index (DLQI) scoring.

Subjects participating in PK sampling were admitted to the clinic on Month 1 Day 1 (M1D1) for PK procedures and were discharged on M2D2. Blood samples for PK analyses were collected on M2D1 and Month 3 Day 1 (M3D1) on an outpatient basis. Subjects were not to take their morning dose until after blood samples were drawn.

A Follow-Up visit occurred 30 ± 3 days after the last dose of study drug.

The endpoints for efficacy were PASI, PGA, and DSQI scores.

1. Psoriasis Area and Severity Index (PASI): The PASI is a measure of the psoriasis disease severity using the average redness, thickness, and scaliness of the lesions (each graded on a 0 to 4 scale), which is weighted by the area of involvement. The PASI combines the assessment of the severity of lesions and the area affected into a single score ranging from 0 (no disease) to 72 (maximal disease).
2. Physicians Global Assessment (PGA): The relative PGA documents the physician's assessment of the subject's psoriasis status. Consideration was given to the percent of body involvement as well as overall induration, scaling, and erythema. The PGA was assessed relative to baseline condition and defined as: (1) clear; (2) excellent; (3) good; (4) fair; (5) poor; and (6) worse.
3. Dermatology Life Quality Index (DLQI): The DLQI is a skin disease-specific instrument designed to assess the impact of the disease on a subject's quality of life (QOL). It is a 10-item questionnaire that assesses 6 different aspects of quality of life: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships, and treatment. Possible DLQI scores range from 0 (no detectable impairment on a subject's QOL) to 30 (extremely large effect on a subject's QOL).

Safety was assessed by standard clinical and laboratory tests (hematology, serum chemistry, and urinalysis), PEs, and reporting of treatment-emergent adverse events (TEAEs). Toxicity grades were defined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. In addition, subjects had liver ultrasound and liver functioning testing assessed for possible steatosis.

Blood samples for determination of PK plasma concentrations of KD025 and its metabolites were collected for maximum concentration (Cmax); time of maximum concentration (Tmax); area under the concentration-time curve (AUC) at 0 to 24 hours, 0 to last, and 0 to infinity (0 to 24, 0 to last, 0 to infinity \[inf\]); half-life (t1/2); and accumulation ratio (metabolic-to-parent drug ratio).

Arms: arm 1: KD025 400 mg QD PO for 12 weeks arm 2: KD025 200 mg BID PO for 12 weeks arm 3: KD025 400 mg BID PO for 12 weeks
Interventions: intervention 1: KD025
Intervention descriptions: intervention 1: None

Protocol documents: