Eli Lilly RHBC

Overview

Status: Recruiting
Keywords: psoriasis , dermatology
IRB Number: 00058072
Specialty: Dermatology
Sub Specialties: Psoriasis and Phototherapy

Brief Summary

 Ixekizumab (LY2439821) is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody that neutralizes the cytokine interleukin-17A (IL-17A, also known as IL-17).  It has a high affinity for and neutralizes the activity of both human and monkey IL‑17.  It has high specificity to IL‑17A (IL-17) and has no cross-reactivity to other IL-17 family members (IL‑17B‑F).  Ixekizumab blocks IL-17 binding to the IL‑17 receptor (IL-17R).  Specific inhibition of IL-17 represents a targeted approach to the management of psoriasis (Ps) and a novel mechanism of action compared to other Ps therapies.  As such, ixekizumab may provide a therapeutic option for patients who are candidates for initial systemic treatment as well as those patients who have lost response, failed to respond, or are intolerant to current marketed drugs.  Ixekizumab may provide an alternative therapy providing a favorable benefit/risk profile.  Specifically, targeting IL-17 with ixekizumab is hypothesized to provide optimal therapeutic benefit while reducing the risk of impacting host defenses, which may be inherent with some other biologic-based immunomodulatory treatments.

The primary objectives of the study are to assess whether 80 mg ixekizumab Q2W or Q4W is:

  • superior to placebo at Week 12 in the treatment of patients with moderate to severe plaque psoriasis as measured by:
    • proportion of patients with an sPGA (0,1) with at least a 2-point improvement from baseline
    • proportion of patients achieving a ≥75% improvement in PASI (PASI 75) from baseline
  • noninferior to etanercept at Week 12 in the treatment of patients with moderate to severe plaque psoriasis as measured by:
    • proportion of patients achieving PASI 75 from baseline
    • proportion of patients with an sPGA (0,1) with at least a 2-point improvement from baseline
  • superior to etanercept at Week 12 in the treatment of patients with moderate to severe plaque psoriasis as measured by:
    • proportion of patients achieving PASI 75 from baseline
    • proportion of patients with an sPGA (0,1) with at least a 2-point improvement from baseline
  • Secondary and Exploratory Objectives are detailed in the protocol summary.

 

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

Contact Information

Name:Sasha Hamel
Phone: 8012132726
Email: sasha.hamel@gmail.com

Inclusion Criteria

Inclusion Criteria

Patients are eligible to be included in the study only if they meet all of the following 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, intrauterine device, vaginal ring, diaphragm- with contraceptive gel, or condom with contraceptive gel

-or-

are women of non–childbearing 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 non–childbearing potential (≥40 mIU/mL)

2. present with chronic plaque Ps based on a confirmed diagnosis of chronic plaque Ps for at least 6 months prior to baseline (Week 0, Visit 2)

3. have ≥10% BSA involvement at screening (Visit 1) and baseline (Week 0, Visit 2)

4. have both an sPGA score of ≥3 and a PASI score ≥12 at screening (Visit 1) and at 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

Exclusion Criteria

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 psoriasis

2. have a history of drug-induced psoriasis had a clinically significant flare of Ps during the 12 weeks prior to baseline (Week 0, Visit 2)

3. Prior use of etanercept.

4. have received systemic nonbiologic psoriasis therapy (including, but not limited to, oral psoralens and ultraviolet A [PUVA] light therapy, cyclosporine, corticosteroids, MTX, 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 [UVB], 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 non-prescription 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 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:  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 α 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.) 

10. had a vaccination with Bacillus Calmette-Guérin (BCG) within 12 months prior to baseline (Week 0, Visit 2) or intend to have vaccination with BCG during the course of the study or within 12 months of completing treatment in this study

11. 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

12. have current or history of lymphoproliferative disease, signs or symptoms of lymphoproliferative disease, or 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.)

13. presence of significant uncontrolled cerebro-cardiovascular (for example, myocardial infarction [MI], unstable angina, unstable arterial hypertension, moderate to severe [New York Heart Association (NYHA) 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

14. have had fluid overload, MI, or new onset ischemic heart disease (e.g,. unstable angina), uncompensated heart failure, or in the opinion of the investigator other serious cardiac disease within 12 weeks prior to baseline (Week 0; Visit 2)

15. 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 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

16. presence or history of demyelinating disorder.

17. had a serious infection (eg, pneumonia, cellulitis, sepsis), have been hospitalized, or have received intravenous (IV) antibiotics for an infection within 12 weeks prior to baseline (Week 0, Visit 2); 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 infection 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 weeks after documented resolution of symptoms

21. have an oral 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 10.3.2.2 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 reading 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 (HIV) serology (positive for HIV 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) HBcAb+ and positive for anti-hepatitis B surface antibody (HBsAb+) with a concentration of HBsAb <200 mIU/mL; or 4) HBcAb+, HBsAb+ (regardless of HBsAb level), and positive for serum hepatitis B virus (HBV) DNA.

(Note: Patients who are negative for hepatitis B surface antigen (HBsAg), HBcAb+, HBsAb+ with a concentration 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 10.3.3.3).

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 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/µL

[27b] lymphocyte count <500 cells/µL

[27c] platelet count <100,000 cells/µL

[27d]      aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level >2.5 times the upper limit of normal (ULN)

[27e] total white blood cell (WBC) count <3000 cells/µL

[27f] hemoglobin level <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 level >2.0 mg/dL

(Note:  The AST and ALT measurements may be repeated once within a week if the initial response exceeds this limit, and the repeat value may be accepted if it is below the limit stated above.  Other laboratory tests should not be repeated unless there is a technical error or clinical reasons 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 known 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 blood of more than 500 mL within the last 4 weeks or intend to donate blood during the course of the study

32. are women who are lactating or breast-feeding

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 are employees of third-party organizations (TPOs) involved in the study

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

36. Have any condition or contraindication as addressed in the local labeling for etanercept that would preclude the patient from participating in this protocol.