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

December 22, 2022 updated by: University Hospitals Cleveland Medical Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Cleveland Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Males or females, ≥ 18 and < 60 years of age at the time of signing the informed consent document.
  2. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
  3. Able to adhere to the study visit schedule and other protocol requirements.
  4. 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).
  5. Diagnosis of chronic plaque psoriasis for at least 12 months prior to Screening.
  6. Have moderate to severe plaque psoriasis at Screening and Baseline as defined by a. BSA ≥5% b. sPGA ≥3 (moderate to severe)
  7. Must be a candidate for phototherapy and systemic (including Otezla) therapy.
  8. Must be in good health (except for psoriasis) as judged by the Investigator, based on medical history and physical examination.
  9. 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:

    1. treated [i.e., cured] basal cell or squamous cell in situ skin carcinomas;

    2. 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Apremilast for Treatment of Psoriasis with the AM-endotype
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
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.
Other Names:
  • Otezla

What is the study measuring?

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).
Time Frame: Baseline, Week 16
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
Time Frame: Baseline, Week 16
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
Time Frame: Baseline, Week 16
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
Time Frame: Baseline, Week 16
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
Time Frame: Baseline, Week 16
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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate Median Changes in Flow Cytometric Quantification of Monocytes
Time Frame: 16 weeks
To assess change in quantitation of additional monocyte and neutrophil markers, including CD18/CD11b and NETotic neutrophils by computing relative percent reduction in circulating CD18/CD11b and NETotic neutrophils for each subject being treated.
16 weeks
Monocyte Transcriptome Biomarkers
Time Frame: 16 weeks
To assess change in expression levels of monocyte transcriptome biomarkers using quantitative PCR to measure changes from baseline to 16 weeks in identified monocyte genes.
16 weeks
Percent Change in Dermatology Life Quality Index (DLQI)
Time Frame: 16 weeks
Calculate the percent change in Dermatology Life Quality Index (DLQI) from baseline to 16 weeks in patients.
16 weeks
Percent Change Between Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI: PSO
Time Frame: 16 weeks
Calculate the percent change Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI: PSO) from baseline to 16 weeks in patients treated with apremilast 30 mg BID
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospitals Cleveland Medical Center

Investigators

  • Study Chair: Kevin Cooper, MD, University Hospitals Cleveland Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2018

Primary Completion (Actual)

September 30, 2021

Study Completion (Actual)

September 30, 2021

Study Registration Dates

First Submitted

October 11, 2017

First Submitted That Met QC Criteria

February 15, 2018

First Posted (Actual)

February 22, 2018

Study Record Updates

Last Update Posted (Actual)

January 20, 2023

Last Update Submitted That Met QC Criteria

December 22, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07-17-33

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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