Icotinib Hydrochloride Cream in Patients With Mild to Moderate Psoriasis

A Single-Center, Randomized, Double-blind, Placebo-Controlled Study to Evaluate Safety, Tolerability and Pharmacokinetics of Icotinib Hydrochloride Cream in Patients With Mild to Moderate Psoriasis

This is a phase I study to evaluate the safety, tolerability and pharmacokinetics of Icotinib Hydrochloride Cream in patients with mild to moderate psoriasis.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: 0.5% Icotinib hydrochloride cream; Drug: Placebo; Drug: 1.0% Icotinib hydrochloride cream; Drug: 2.0% Icotinib hydrochloride cream; Drug: 4.0% Icotinib hydrochloride cream

Detailed Description

Icotinib Hydrochloride is a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, which has been approved for the treatment of advanced nonsmall- cell lung cancer (NSCLC) in China in its oral form. As EGFR is implicated in the pathogenesis of psoriasis, icotinib hydrochloride is being developed as a cream for the treatment of mild to moderate psoriasis. This is a single-center, randomized, doubleblind, placebo-controlled study of 0.5%, 1.0%, 2.0%, 4.0% icotinib hydrochloride cream by topical administration. Icotinib hydrochloride cream will be applied to subjects with mild to moderate psoriasis. Approximately 40 subjects will be enrolled.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • The Second Affiliated Hospital of Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of plaque psoriasis for at least six months with multiple treatable area (i.e. the lesion should not only on the face, scalp, genitals or skinfolds) of plaque psoriasis covering less than 10% of the total Body Surface Area (BSA), affected area on the limb and/or trunk≥ 1% BSA. A Target Plaque Area (TPA)≥9 cm2, with a Target Plaque Severity Score(TPSS)≥ 5, and induration subscore≥2.
• Male participants should be ≥ 50 kg, female participants should be ≥ 45 kg; BMI should be between 19 and 28 kg/m2 (inclusive)
• In good health, with no history of diseases of major organs and no abnormality found on physical examination and vital signs
• Non-allergic, with no known history of drug allergy
• Men and women of childbearing potential must agree to use a contraceptive regimen agreed by the doctor during the trial. Female subjects that are on hormonal contraceptives must continue using the same hormonal contraceptive as that was used in the past 3 months, with the same route of administration and the same dose during the study
• Have signed a written informed consent before entering the study

Exclusion Criteria:

• Psoriasis guttata, psoriasis punctata, erythrodermic psoriasis, pustular psoriasis, psoriasis arthritis
• Any dermatological disease that might interfere psoriasis clinical evaluation or bring the subject in danger, or have other serious dermatological disease other than psoriasis.
• Have received underlying treatments before entering the trial:

Topical anti-psoriasis treatment in 2 weeks, e.g. corticosteroids, retinoids acid, anthranol, tars, keratolytics. Vitamin D analogues or local immune regulator treatment in 4 weeks; Emollient or cosmetics in 24 hours; Any psoriasis vaccine, or have participated in any psoriasis vaccine trial; Biologics treatment in 12 weeks, e.g. Alefacept, Etanercept, Infliximab, Adalimumab, Ustekinumab, Efalizumab; Any phototherapy or systemic treatment in 4 weeks, e.g. corticosteroids, methotrexate, retinoids acids, ciclosporin; Long time exposure to natural light or artificial UV, or will have such exposure; Use of drug known to harm certain organ in 12 weeks; Participated in any clinical trial in 4 weeks, or have plan to participate any trial during treatment period;

• Any clinically significant central nervous, cardiac, hepatic, renal, gastrointestinal, respiratory, metabolic or musculoskeletal system disease history, or other pathological/physiological condition that might disrupt the trial result
• Alanine transaminase(ALT), aspartate aminotransferase (AST), total bilirubin>1.5 Upper Limit Normal (ULN), creatinine>ULN
• History of postural hypotension, or allergic diseases (asthma, urticaria, atopic dermatitis or rhinitis)
• Pulmonary disease demonstrated by chest X-ray examination
• Physically or mentally disabled
• Positive for Hepatitis B Surface Antigen (HBsAg), hepatitis C or anti-HIV test
• Know allergic to active ingredient or excipient of the investigational product
• Excessive smoker(>10 cigarettes per day), or excessive alcohol intake (>15g absolute alcohol per day, equal to 450ml beer, 150ml wine or 50ml low-alcohol Chinese liquor)
• Excessive drinking of tea, coffee or caffein-containing beverage (>8 glasses per day)
• Drug abuser
• Poor compliance
• Under gestation or lactation period
• Other subject that in the investigator's opinion unsuitable to be enrolled

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1-Experimental; 8 patients with mild to moderate psoriasis will be randomized to receive 0.5% Icotinib hydrochloride cream, applied twice daily for 4 consecutive weeks. The drug will be applied topically to the psoriasis site.	Drug: 0.5% Icotinib hydrochloride cream; Topical administration for twice daily; Other Names: no other name
PLACEBO_COMPARATOR: Cohort 1-Placebo; 2 patients with mild to moderate psoriasis will be randomized to receive matching placebo, applied twice daily for 4 consecutive weeks. The drug will be applied topically to the psoriasis site.	Drug: Placebo; Topical administration for twice daily; Other Names: Blank cream
EXPERIMENTAL: Cohort 2-Experimental; 8 patients with mild to moderate psoriasis will be randomized to receive 1.0% Icotinib hydrochloride cream, applied twice daily for 4 consecutive weeks. The drug will be applied topically to the psoriasis site.	Drug: 1.0% Icotinib hydrochloride cream; Topical administration for twice daily; Other Names: no other name
PLACEBO_COMPARATOR: Cohort 2-Placebo; 2 patients with mild to moderate psoriasis will be randomized to receive matching placebo, applied twice daily for 4 consecutive weeks. The drug will be applied topically to the psoriasis site.	Drug: Placebo; Topical administration for twice daily; Other Names: Blank cream
EXPERIMENTAL: Cohort 3-Experimental; 8 patients with mild to moderate psoriasis will be randomized to receive 2.0% Icotinib hydrochloride cream, applied twice daily for 4 consecutive weeks. The drug will be applied topically to the psoriasis site.	Drug: 2.0% Icotinib hydrochloride cream; Topical administration for twice daily; Other Names: no other name
PLACEBO_COMPARATOR: Cohort 3-Placebo; 2 patients with mild to moderate psoriasis will be randomized to receive matching placebo, applied twice daily for 4 consecutive weeks. The drug will be applied topically to the psoriasis site.	Drug: Placebo; Topical administration for twice daily; Other Names: Blank cream
EXPERIMENTAL: Cohort 4-Experimental; 8 patients with mild to moderate psoriasis will be randomized to receive 4.0% Icotinib hydrochloride cream, applied twice daily for 4 consecutive weeks. The drug will be applied topically to the psoriasis site.	Drug: 4.0% Icotinib hydrochloride cream; Topical administration for twice daily; Other Names: no other name
PLACEBO_COMPARATOR: Cohort 4-Placebo; 2 patients with mild to moderate psoriasis will be randomized to receive matching placebo, applied twice daily for 4 consecutive weeks. The drug will be applied topically to the psoriasis site.	Drug: Placebo; Topical administration for twice daily; Other Names: Blank cream

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety in patients with mild to moderate psoriasis	Incidence and severity of Adverse Events (AE), Physical Examinations, Vital signs (temperature, Heart Rate (HR), BP and respiration); Clinical laboratory assessments (serum chemistry, hematology, C-reactive protein , fecal and urinalysis); ECG;	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerance-related skin reactions in patients with mild to moderate psoriasis at the treatment site	Skin irritation and allergy observation (including redness, swelling,rash, itching, pain) recorded by grades	28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lesion severity	Erythema , scale , thickness of target site on patients with mild to moderate psoriasis	28 days
Lesion area		28 days
Psoriasis Area and Severity Index (PASI) Scores in patients with mild to moderate psoriasis		28 days
Physician's Global Assessment(PGA) in patients with mild to moderate psoriasis		28 days
Dermatology Life Quality Index (DLQI) in patients with mild to moderate psoriasis		28 days
Time maximum concentration observed(tmax) of single-dose Icotinib Hydrochloride Cream in patients with mild to moderate psoriasis		12 hours
Peak plasma concentration (Cmax) of single-dose Icotinib Hydrochloride Cream in patients with mild to moderate psoriasis		12 hours
Area under the plasma concentration versus time curve(AUC) of single-dose Icotinib Hydrochloride Cream from zero(0) hours to time (t) in patients with mild to moderate psoriasis		12 hours
Area under the plasma concentration versus time curve(AUC) of single-dose Icotinib Hydrochloride Cream from zero (0) hours to infinity (∞) in patients with mild to moderate psoriasis		12 hours
Half life(t1/2) of single-dose Icotinib Hydrochloride Cream in patients with mild to moderate psoriasis		12 hours
Time maximum concentration observed(tmax) of repeat-dose Icotinib Hydrochloride Cream in patients with mild to moderate psoriasis		24 hours
Stable peak plasma concentration (Cmaxss) of repeat-dose Icotinib Hydrochloride Cream in patients with mild to moderate psoriasis		24 hours
Area under the plasma concentration versus time curve(AUC) of repeat-dose Icotinib Hydrochloride Cream from zero(0) hours to time (t) in patients with mild to moderate psoriasis		24 hours
Area under the plasma concentration versus time curve(AUC) of repeat-dose Icotinib Hydrochloride Cream from zero (0) hours to infinity (∞) in patients with mild to moderate psoriasis		24 hours
Half life(t1/2) of repeat-dose Icotinib Hydrochloride Cream in patients with mild to moderate psoriasis		24 hours

Collaborators and Investigators

• Sponsor: Betta Pharmaceuticals Co., Ltd.
• Collaborators: Tigermed Consulting Co., Ltd
• Investigators: Principal Investigator: Min Zheng, The Second Affiliated Hospital of Zhejiang University School of Medicine (SAHZU); Principal Investigator: Zourong Ruan, The Second Affiliated Hospital of Zhejiang University School of Medicine (SAHZU)

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 17, 2016
• Primary Completion (ACTUAL): June 8, 2017
• Study Completion (ACTUAL): June 8, 2017

Study Registration Dates

• First Submitted: June 11, 2016
• First Submitted That Met QC Criteria: June 11, 2016
• First Posted (ESTIMATE): June 15, 2016

Study Record Updates

• Last Update Posted (ACTUAL): July 17, 2017
• Last Update Submitted That Met QC Criteria: July 12, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: phase 1; EGFR inhibitor; psoriasis; topical agent
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: BD-ICC-I01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO