I1F-MC-RHBL

Overview

Status: Not yet recruiting
Keywords: Evaluations of Ixekizumab following Subcutaneous Administration Using Prefilled Syringe or Auto-Injector in Patients with Moderate-to-Severe Plaque Psoriasis
IRB Number: 00064051
Specialty: Dermatology
Sub Specialties: Psoriasis and Phototherapy

Brief Summary

 

Objectives: The primary objective of the study is to evaluate the effect of drug delivery device, either by prefilled

syringe or by auto-injector, on the pharmacokinetics (PK) of ixekizumab after the administration of the starting

dose (160 mg) as subcutaneous (SC) injection in patients with moderate-to-severe plaque psoriasis (Ps).

The secondary objectives of the study are as follows:

 To evaluate the effect of body weight and site of injection (arm, thigh, or abdomen) on the PK of

ixekizumab following single dose SC administration via prefilled syringe or auto-injector

 To summarize the effect of multiple-dose ixekizumab SC administration (80 mg every 2 weeks [Q2W])

via prefilled syringe or auto-injector at Week 12 on the following outcomes:

     o Proportion of patients with a static Physician Global Assessment (sPGA) (0,1) with at least a 2-point

     improvement from baseline

     o Proportion of patients with sPGA (0)

     o Proportion of patients achieving a ≥75% improvement in Psoriasis Area and Severity Index

     (PASI 75)

     o Proportion of patients achieving a ≥90% improvement in PASI (PASI 90), and 100% improvement in

     PASI (PASI 100)

 To evaluate the incidence of development of anti-ixekizumab antibodies over 12 weeks in patients

administered ixekizumab SC via prefilled syringe or auto-injector

 To evaluate the frequency of device operation failures over 12 weeks in patients administered SC

ixekizumab via prefilled syringe or auto-injector

 To evaluate ease of use and confidence of ixekizumab SC administrations via auto-injector using the

Subcutaneous Administration Assessment Questionnaire (SQAAQ) at Weeks 0, 4, and 8.

The exploratory objectives of the study are as follows:

 To characterize the effect of baseline hand disability as measured by a hand disability evaluation

(Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands

[M-SACRAH]) questionnaire on the results of the SQAAQ for the prefilled syringe or auto-injector

 To evaluate ease of use and confidence of ixekizumab SC administrations via prefilled syringe using the

SQAAQ at Weeks 0, 4, and 8

 To evaluate SQAAQ responses at Week 8 compared to Week 20 in the subgroup of patients administered

ixekizumab SC via auto-injector during the Treatment Period (first 12 weeks) and then administered

ixekizumab SC via prefilled syringe in the Optional Safety Extension Period.

Principal Investigator: Kristina Duffin
Department: Dermatology
Co Investigator: Gerald Krueger

Contact Information

Name:Melissa Weidner
Phone: 801-581-6477
Email: Melissa.Weidner@hsc.utah.edu

Inclusion Criteria

 

[1] Are male or female patients 18 years or older.

[1a] Male patients agree to use a reliable method of birth control during the

study.

[1b] Female patients:

Are women of childbearing potential who test negative for pregnancy and

agree to use a reliable method of birth control or remain abstinent during the

study and for at least 12 weeks following the last dose of investigational

product, whichever is longer. Methods of contraception considered

acceptable include oral contraceptives, contraceptive patch, injectable or

implantable contraceptives, intrauterine device, vaginal ring, diaphragm with

contraceptive gel, or condom with contraceptive foam.

-or-

Are women of nonchildbearing potential, defined as:

Women who have had surgical sterilization (hysterectomy, bilateral

oophorectomy, or tubal ligation);

-or-

Women who are ≥60 years of age;

-or-

Women ≥40 and <60 years of age who have had a cessation of menses for

≥12 months and a follicle-stimulating hormone (FSH) test confirming

nonchildbearing potential (≥40 mIU/mL).

[2] Present with chronic plaque Ps based on a confirmed diagnosis of chronic

Ps vulgaris for at least 6 months prior to baseline (Week 0; Visit 2).

[3] Have ≥10% body surface area (BSA) involvement at screening (Visit 1) and

baseline (Week 0; Visit 2).

[4] Have both an sPGA score of ≥3 and PASI score ≥12 at screening (Visit 1) and

baseline (Week 0; Visit 2).

[5] Are a candidate for phototherapy and/or systemic therapy.

[6] Have given written informed consent approved by Lilly, or its designee, and

the institutional review board (IRB)/ERB governing the site.

[7] Are able and willing to inject study drug by themselves (or have an assistant

who will inject study drug) and able and willing to complete all study

procedures.

[8] Are able and willing to have blood drawn for PK sampling per protocol.

Exclusion Criteria

 

Patients will be excluded from the study if they meet any of the following criteria:

[1] Have pustular, erythrodermic, and/or guttate forms of Ps.

[2] Have a history of drug-induced Ps.

[3] Had a clinically significant flare of Ps during the 12 weeks prior to baseline

(Week 0; Visit 2).

[4] Have received systemic nonbiologic Ps therapy (including, but not limited to,

oral psoralen and ultraviolet A [PUVA] light therapy; cyclosporine;

corticosteroids; methotrexate; oral retinoids; mycophenolate mofetil;

thioguanine; hydroxyurea; sirolimus; azathioprine; fumaric acid derivatives;

or 1, 25 dihydroxy vitamin D3 and analogues) or phototherapy (including

either oral and topical PUVA light therapy, ultraviolet B or self-treatment with

tanning beds or therapeutic sunbathing) within 4 weeks prior to baseline

(Week 0; Visit 2);

-or had

topical Ps treatment (including, but not limited to, corticosteroids,

anthralin, calcipotriene, topical vitamin D derivatives, retinoids, tazarotene,

emollients and other nonprescription topical products containing urea,

>3% salicylic acid, or alpha- or beta-hydroxyl acids, and medicated shampoos

[for example those that contain >3% salicylic acid, corticosteroids, coal tar, or

vitamin D3 analogues]) within the previous 2 weeks prior to baseline

(Week 0; Visit 2)

Exceptions: Class 6 (mild, such as desonide) or Class 7 (least potent, such as

hydrocortisone) topical steroids will be permitted for use limited to the face,

axilla, and/or genitalia.

[5] Cannot avoid excessive sun exposure or use of tanning booths for at least

4 weeks prior to baseline (Week 0; Visit 2) and during the study.

[6] Have concurrent or recent use of any biologic agent within the following

washout periods: etanercept <28 days; infliximab, adalimumab, or alefacept

<60 days; golimumab <90 days; ustekinumab <8 months; rituximab or

efalizumab <12 months; or any other biologic agent <5 half-lives prior to

baseline (Week 0; Visit 2).

[7] Have ever received natalizumab or other agents that target alpha-4-integrin.

[8] Have previously completed or withdrawn from this study, participated in any

other study with ixekizumab, or have participated in any study investigating

other IL-17 antagonists.

[9] Have a known allergy or hypersensitivity to any biologic therapy that would

pose an unacceptable risk to the patient if participating in this study.

[10] Had a live vaccination within 12 weeks prior to baseline (Week 0; Visit 2), or

intend to have a live vaccination during the course of the study, or within

12 months of completing treatment in this study, or have participated in a

vaccine clinical study within 12 weeks prior to baseline. Investigators should

review the vaccination status of their patients and follow the local guidelines

for adult vaccination with nonlive vaccines intended to prevent infectious

disease prior to therapy.

(Note: Killed/Inactive or subunit vaccines are expected to be safe; however,

their efficacy with concomitant ixekizumab treatment is unknown.)

[11] Had a vaccination with Bacillus Calmette-Guérin (BCG) within 12 months

prior to baseline (Week 0; Visit 2), or intend to have a vaccination with BCG

during the course of the study, or within 12 months of completing treatment in

this study.

[12] Had any major surgery within 8 weeks prior to baseline (Week 0; Visit 2), or

will require such during the study that, in the opinion of the investigator in

consultation with Lilly or its designee, would pose an unacceptable risk to the

patient.

[13] Have current or a history of lymphoproliferative disease; or signs or

symptoms of lymphoproliferative disease; or have active or history of

malignant disease.

(Note: Patients with successfully treated basal-cell carcinoma [no more than

3], squamous-cell carcinoma of the skin, or cervical carcinoma in situ, with no

evidence of recurrence within the 5 years prior to baseline [Week 0; Visit 2]

may participate in the study).

[14] Have presence of significant uncontrolled cerebrocardiovascular (for example,

myocardial infarction [MI], unstable angina, unstable arterial hypertension,

moderate-to-severe [New York Heart Association Class III/IV] heart failure,

or cerebrovascular accident [CVA]), respiratory, hepatic, renal,

gastrointestinal, endocrine, hematologic, neurologic or neuropsychiatric

disorders, or abnormal laboratory values at screening that, in the opinion of

the investigator, pose an unacceptable risk to the patient if participating in the

study or of interfering with the interpretation of data.

[15] Have a history of uncompensated heart failure, fluid overload, or MI, or

evidence of new-onset ischemic heart disease or other serious cardiac disease,

within 12 weeks prior to baseline (Week 0; Visit 2).

[16] Have presence of significant uncontrolled neuropsychiatric disorder, have

history of a suicide attempt, have a score of 3 on Item 12 (Thoughts of Death

or Suicide) of the Quick Inventory of Depressive Symptomatology – Self

Report (16 items) (QIDS-SR16) at screening (Visit 1) or baseline (Week 0;

Visit 2), or are clinically judged by the investigator to be at risk for suicide.

[17] Had a serious infection (for example, pneumonia, cellulitis), have been

hospitalized, or have received intravenous antibiotics for an infection, within

12 weeks prior to baseline (Week 0; Visit 2), or had a serious bone or joint

infection within 24 weeks prior to baseline, or have ever had an infection of

an artificial joint, or are immunocompromised to an extent such that

participation in the study would pose an unacceptable risk to the patient.

[18] Have or had an infection typical of an immunocompromised host, and/or that

occurs with increased incidence in an immunocompromised host (including,

but not limited to, Pneumocystis jirovecii pneumonia, histoplasmosis, or

coccidioidomycosis); or have a known immunodeficiency.

[19] Have or had a herpes zoster or any other clinically apparent varicella-zoster

virus infection within 12 weeks of baseline (Week 0; Visit 2).

[20] Have any other active or recent infection within 4 weeks of baseline (Week 0;

Visit 2) that, in the opinion of the investigator, would pose an unacceptable

risk to the patient if participating in the study; these patients may be

rescreened (1 time) 4 or more weeks after documented resolution of

symptoms.

[21] Have a body temperature ≥38°C (100.5°F) at baseline (Week 0; Visit 2); these

patients may be rescreened (1 time) ≥4 weeks after documented resolution of

elevated temperature.

[22] Have evidence or suspicion of active or latent TB (refer to Section 10.4.2.2 for

details on determining full TB exclusion criteria).

[23] Have uncontrolled arterial hypertension characterized by a systolic blood

pressure (BP) >160 mm Hg or diastolic BP >100 mm Hg.

 

(Note: Determined by 2 consecutive elevated readings. If an initial BP

reading exceeds this limit, the BP may be repeated once after the patient has

rested sitting for ≥10 minutes. If the repeat value is less than the criterion

limits, the second value may be accepted.)

[24] Are positive for human immunodeficiency virus serology (HIV), ie, positive

for human immunodeficiency virus antibody (HIVAb).

[25] Have evidence of or test positive for hepatitis B by any of the following

criteria: 1) positive for hepatitis B surface antigen (HBsAg+), 2) positive for

anti-hepatitis B core antibody (HBcAb+) and negative for anti-hepatitis B

surface antibody (HBsAb–), 3) positive for anti-hepatitis B core antibody

(HBcAb+) and positive for anti-hepatitis B surface antibody (HBsAb+) with a

concentration of HBsAb <200 mIU/mL, or 4) positive for anti-hepatitis B core

antibody, positive for anti-hepatitis B surface antibody (regardless of HBsAb

level), and positive for serum hepatitis B virus (HBV) DNA.

(Note: Patients who are negative for hepatitis B surface antigen (HBsAg–),

positive for anti-hepatitis B core antibody (HBcAb+), positive for antihepatitis

B surface antibody (HBsAb+) with a level of HBsAb ≥200 mIU/mL,

and negative for serum HBV DNA may participate in the study. Patients who

meet these criteria at screening will be identified by the central laboratory and

will be monitored during the study as detailed in Section 10.4.3.3.

[26] Have evidence of or test positive for hepatitis C virus (HCV). A positive test

for HCV is defined as: 1) positive for hepatitis C antibody (anti-HCV Ab),

and 2) positive via a confirmatory test for HCV (for example, HCV

polymerase chain reaction).

[27] Have clinical laboratory test results at screening that are outside the normal

reference range for the population and are considered clinically significant,

and/or have any of the following specific abnormalities:

[27a] Neutrophil count <1500 cells/L

[27b] Lymphocyte count <500 cells/L

[27c] Platelet count <100,000 cells/L

[27d] Aspartate aminotransferase (AST) or alanine aminotransferase

(ALT) >2.5 times the upper limit of normal (ULN)

[27e] Total white blood cell (WBC) count <3000 cells/L

[27f] Hemoglobin <8.5 g/dL (85.0 g/L) for male patients and <8.0 g/dL

(80 g/L) for female patients

[27g] Serum creatinine >2.0 mg/dL.

(Note: The AST and ALT may be repeated once within a week if the initial

response exceeds this limit, and the repeat value may be used to assess

eligibility. Other laboratory tests should not be repeated unless there is a

technical error or clinical reason to believe a result may be erroneous.)

[28] Have electrocardiogram (ECG) abnormalities that are considered clinically

significant and would pose an unacceptable risk to the patient if participating

in the study.

[29] Have allergy to rubber or latex.

[30] Have any other condition that precludes the patient from following and

completing the protocol, in the opinion of the investigator.

[31] Have donated more than 500 mL of blood within the last 4 weeks, or intend to

donate blood during the course of the study.

[32] Are women who are lactating or breastfeeding.

[33] Are investigator site personnel directly affiliated with this study and/or their

immediate families. Immediate family is defined as a spouse, parent, child, or

sibling, whether biological or legally adopted.

[34] Are Lilly employees or its designee.

[35] Are currently enrolled in, or discontinued from a clinical trial involving an

investigational product or nonapproved use of a drug or device, within the last

4 weeks or a period of at least of 5 half-lives of the last administration of the

drug, whichever is longer, or concurrently enrolled in any other type of

medical research judged not to be scientifically or medically compatible with

this study.