Monocyte Biomarkers in Moderate to Severe Plaque Psoriasis Subjects Treated With Apremilast

Study Overview
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Brief Summary
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This is an open label pilot study of the impact of treatment with standard dosing of Otezla for 16 weeks on AM-endotype psoriasis patients, identified by elevated (>150% of normal): 1.) Intermediate (CD14++CD16+) monocytes, or 2.) circulating monocyte doublets, or 3.) circulating monocyte-platelet aggregates (MPA). Approximately 25 psoriasis patients with the AM-endotype will be followed during treatment over 16 weeks with 4 monthly individual blood draws will be enrolled. All treated psoriasis subjects will receive apremilast through Week 16.

Official Title
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An Investigator Initiated Study of Monocyte Biomarkers in Moderate to Severe Plaque Psoriasis Subjects Treated With Apremilast

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: Apremilast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females, ≥ 18 and < 60 years of age at the time of signing the informed consent document. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted. Able to adhere to the study visit schedule and other protocol requirements. Patients must exhibit AM-endotype psoriasis patients, identified by elevated (>150% of normal) levels of any one of the following criteria: 1.) Intermediate (CD14++CD16+) monocytes, or 2.) circulating monocyte doublets, or 3.) circulating monocyte-platelet aggregates (MPA). Diagnosis of chronic plaque psoriasis for at least 12 months prior to Screening. Have moderate to severe plaque psoriasis at Screening and Baseline as defined by a. BSA ≥5% b. sPGA ≥3 (moderate to severe) Must be a candidate for phototherapy and systemic (including Otezla) therapy. Must be in good health (except for psoriasis) as judged by the Investigator, based on medical history and physical examination. Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. While on investigational product and for at least 28 days after taking the last dose of investigational product, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options described below: Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy; OR Option 2: Male or female condom (latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]; PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide. The female subject's chosen form of contraception must be effective by the time the female subject is randomized into the study (for example, hormonal contraception should be initiated at least 28 days before randomization Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (male latex condom or non-latex condom NOT made out of natural [animal] membrane [for example, polyurethane]) while on investigational product and for at least 28 days after the last dose of investigational product. Exclusion Criteria: 1. Other than psoriasis, history of any clinically significant (as determined by the Investigator) cardiac (clinically advanced cardiovascular disease including; Stent, past history of MI, thrombotic event or arterial calcification), endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major uncontrolled disease. 2. Any condition, including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if he/she were to participate in the study. 3. Any condition, including other inflammatory diseases or dermatologic conditions that confound the ability to interpret data from the study. 4. Prior history of suicide attempt at any time in the subject's life time prior to screening or randomization, or major psychiatric illness requiring hospitalization within the last 3 years. 5. Pregnant or breast feeding. 6. Have failed more than 3 systemic agents for treatment of psoriasis. 7. History of allergy to any component of Apremilast. 8. Hepatitis B surface antigen positive at Screening. 9. Anti-hepatitis C antibody positive at Screening. 10. Had a serious infection (including, but not limited to, hepatitis, pneumonia, sepsis, cellulitis, meningitis or pyelonephritis) or have been hospitalized for an infection. Subject must be cured of infection > 4 weeks before Screening. 11. Have a history of, or ongoing, chronic or recurrent infectious disease, including, but not limited to, chronic renal infection, chronic chest infection (e.g., bronchiectasis), sinusitis, recurrent urinary tract infection (e.g., recurrent pyelonephritis, chronic nonremitting cystitis), an open, draining, or infected skin wound or ulcer. 12. Had a Bacillus Calmette-Guérin (BCG) vaccination within 1 year prior to screening. 13. History of positive human immunodeficiency virus (HIV), or have congenital or acquired immunodeficiency (e.g., common variable immunodeficiency disease). 14. Active substance abuse or a history of substance abuse within 6 months prior to Screening. 15. Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening. Any treatment and cure for such infections must have been completed at least 4 weeks prior to Screening. 16. Malignancy or history of malignancy, except for: treated [i.e., cured] basal cell or squamous cell in situ skin carcinomas; treated [i.e., cured] cervical intraepithelial neoplasia [CIN] or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years. 17. Topical therapy within 2 weeks of study entry (including, but not limited to, topical corticosteroids, retinoids or vitamin D analog preparations, tacrolimus, pimecrolimus, or anthralin/dithranol). Exceptions: low-potency corticosteroids to cyclosporine, corticosteroids, methotrexate, retinoids, mycophenolate, thioguanine, hydroxyurea, sirolimus, sulfasalazine, azathioprine, fumaric acid esters) will be allowed as background therapy and restricted to treatment of the face, axillae, and groin in accordance with the manufacturers' suggested usage during the course of the study (this restricted usage should be documented). Subjects with scalp psoriasis will be permitted to use coal tar shampoo and/or salicylic acid scalp preparations on scalp lesions. An unmedicated skin moisturizer (eg, Eucerin®) will be also permitted for body lesions only. Subjects should not use these topical treatments within 24 hours prior to the clinic visit. 18. Systemic therapy for psoriasis within 4 weeks prior to study entry (including, but not limited to, cyclosporine, corticosteroids, methotrexate, retinoids, mycophenolate, thioguanine, hydroxyurea, sirolimus, sulfasalazine, azathioprine, and fumaric acid esters). 19. Use of phototherapy within 4 weeks prior to study entry. 20. Use of any investigational drug within 4 weeks prior to study entry, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer). 21. Prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light sources. 22. Prior treatment with Apremilast 23. Inability to wash out from any topical treatment(s) (two weeks prior to entering the study) or all systemic therapies, including orals and biologics (e.g., TNF inhibitors IL-17 inhibitors, IL-12/23 inhibitors, 4 weeks).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is an open label pilot study of the impact of treatment with standard dosing of APM for 16 weeks on AM-endotype psoriasis patients, identified by elevated (>150% of normal): 1.) Intermediate (CD14++CD16+) monocytes % of cells in circulation, or 2.) circulating monocyte doublets % of adherent monocyte-monocyte pairs, or 3.) circulating monocyte-platelet aggregates (MPA) % monocytes adherent to platelets.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apremilast for Treatment of Psoriasis with the AM-endotype<br>Psoriasis patients with the AM-endotype will be followed during treatment over 16 weeks with 5 monthly individual blood draws will be enrolled. | Drug: Apremilast<br>* Apremilast will be given as approved by the FDA for the treatment of moderate to severe plaque psoriasis. An initial dosage titration from Day 1 (10mg) to Day 5 (30mg). Following the titration, the recommended maintenance dosage of 30 mg twice daily taken orally starting on Day 6 will be dispensed, as per labeled indication.<br>* Other names: Otezla;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Outcome Measure Will be to Evaluate Change in Aberrant Inflammatory Profiles of Activated Blood Monocytes (Aberrant-monocyte Endotype Patients (AM-endotype). | For each subject, we will identify a target biomarker of abnormally elevated monocytes, among 1.) intermediate, or 2.) doublets, or 3.) platelet doubles. Each subject will thus have one identified monocyte biomarker for which relative percent change will be its basis for analysis in the primary outcome measure. We will specifically assess change from baseline to 16 weeks by computing relative percent reduction for each subject being treated. Note for example that a change of 1.5% to 1.2% is (1 - (1.2/1.5))*100% = 20% reduction. The median and other summary statistics of these percent change values will be computed. Wilcoxon's signed rank test will be used to evaluate the null hypothesis of the median percent change being 0. | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum Myeloperoxidase | To assess change in serum myeloperoxidase in the identified patient AM-endotype computing relative percent reduction for each subject being treated and serum marker. The median and other summary statistics of these percent change values will be computed | Baseline, Week 16 | 
| Change in TNF Alpha | To assess change in in the identified patient AM-endotype computing relative percent reduction for each subject being treated and serum marker. The median and other summary statistics of these percent change values will be computed | Baseline, Week 16 | 
| Change in IL-17 | To assess change in IL-17 in the identified patient AM-endotype computing relative percent reduction for each subject being treated and serum marker. The median and other summary statistics of these percent change values will be computed | Baseline, Week 16 | 
| Change in Tissue Factor | To assess change in Tissue Factor in the identified patient AM-endotype computing relative percent reduction for each subject being treated and serum marker. The median and other summary statistics of these percent change values will be computed | Baseline, Week 16 |