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CompletedNCT03442088Updated Jan 20, 2023Results posted

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

A Phase 2 interventional study of Apremilast in Plaque Psoriasis, sponsored by University Hospitals Cleveland Medical Center. Completed at 1 site in United States. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2023-01-20.

Sponsored by University Hospitals Cleveland Medical Center · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
28
Allocation
Not applicable
Ages
18 Years to 60 Years
Sex
All
01

Study summary

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.

02

Conditions studied

  • Plaque Psoriasis

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03

Who can participate

Ages eligible
18 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.

      1. 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.
      1. Any condition, including other inflammatory diseases or dermatologic conditions that confound the ability to interpret data from the study.
      1. 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.
      1. Pregnant or breast feeding.
      1. Have failed more than 3 systemic agents for treatment of psoriasis.
      1. History of allergy to any component of Apremilast.
      1. Hepatitis B surface antigen positive at Screening.
      1. Anti-hepatitis C antibody positive at Screening.
      1. 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.
      1. 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.
      1. Had a Bacillus Calmette-Guérin (BCG) vaccination within 1 year prior to screening.
      1. History of positive human immunodeficiency virus (HIV), or have congenital or acquired immunodeficiency (e.g., common variable immunodeficiency disease).
      1. Active substance abuse or a history of substance abuse within 6 months prior to Screening.
      1. 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.
      1. Malignancy or history of malignancy, except for:
      2. treated [i.e., cured] basal cell or squamous cell in situ skin carcinomas;

      3. 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.

        1. 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.
        1. 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).
        1. Use of phototherapy within 4 weeks prior to study entry.
        1. Use of any investigational drug within 4 weeks prior to study entry, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).
        1. Prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light sources.
        1. Prior treatment with Apremilast
        1. 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).
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
28 participants (actual)

Study arms

  • 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

Interventions

  • DrugApremilast

    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.

    Also known as: Otezla

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline, Week 16

Secondary outcomes

  1. 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

    Time frame: Baseline, Week 16

  2. 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

    Time frame: Baseline, Week 16

  3. 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

    Time frame: Baseline, Week 16

  4. 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

    Time frame: Baseline, Week 16

Other outcomes

  1. Evaluate Median Changes in Flow Cytometric Quantification of Monocytes

    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.

    Time frame: 16 weeks

  2. Monocyte Transcriptome Biomarkers

    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.

    Time frame: 16 weeks

  3. Percent Change in Dermatology Life Quality Index (DLQI)

    Calculate the percent change in Dermatology Life Quality Index (DLQI) from baseline to 16 weeks in patients.

    Time frame: 16 weeks

  4. Percent Change Between Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI: PSO

    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

    Time frame: 16 weeks

06

Results

Posted Jan 20, 2023

Participant flow

Participant flow — Overall Study
MilestoneApremilast for Treatment of Psoriasis With the AM-endotype
Started28
Completed23
Not completed5
Withdrew: Adverse event1
Withdrew: Lack of efficacy2
Withdrew: Lost to follow-up2

Outcome measures

PrimaryThe 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.

Time frame:
Baseline, Week 16
Reported as:
Mean · Percent change
The Primary Outcome Measure Will be to Evaluate Change in Aberrant Inflammatory Profiles of Activated Blood Monocytes (Aberrant-monocyte Endotype Patients (AM-endotype).
Percent changeApremilast for Treatment of Psoriasis With the AM-endotype
Baseline0.5665 ± 0.5135
Week 160.1715 ± 0.2635
Statistical analysis
  • Apremilast for Treatment of Psoriasis With the AM-endotype · Wilcoxon (Mann-Whitney) · p = 0.0001 · Mean difference (final values): -0.272
SecondaryChange 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

Time frame:
Baseline, Week 16
Reported as:
Mean · Pg/mL
Change in Serum Myeloperoxidase
Pg/mLApremilast for Treatment of Psoriasis With the AM-endotype
Baseline24198 ± 3835
Week 1624294 ± 4722
Statistical analysis
  • Apremilast for Treatment of Psoriasis With the AM-endotype · t-test, 2 sided · p = 0.934 · Mean difference (final values): 95.98 · 95% CI -2324 to 2516
SecondaryChange 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

Time frame:
Baseline, Week 16
Reported as:
Mean · Pg/mL
Change in TNF Alpha
Pg/mLApremilast for Treatment of Psoriasis With the AM-endotype
Baseline14.95 ± 4.017
Week 1614.26 ± 3.383
Statistical analysis
  • Apremilast for Treatment of Psoriasis With the AM-endotype · t-test, 2 sided · p = 0.1632 · Mean difference (final values): -0.6878 · 95% CI -1.685 to 0.3097
SecondaryChange 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

Time frame:
Baseline, Week 16
Reported as:
Mean · Pg/mL
Change in IL-17
Pg/mLApremilast for Treatment of Psoriasis With the AM-endotype
Baseline1.513 ± 5.76
Week 16-0.8315 ± 5.824
Statistical analysis
  • Apremilast for Treatment of Psoriasis With the AM-endotype · t-test, 2 sided · p = 0.1063 · Mean difference (final values): -2.344 · 95% CI -5.248 to 0.5992
SecondaryChange 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

Time frame:
Baseline, Week 16
Reported as:
Mean · Pg/mL
Change in Tissue Factor
Pg/mLApremilast for Treatment of Psoriasis With the AM-endotype
Baseline72.28 ± 23.72
Week 1675.52 ± 28.03
Statistical analysis
  • Apremilast for Treatment of Psoriasis With the AM-endotype · t-test, 2 sided · p = 0.5611 · Mean difference (final values): 3.24 · 95% CI -8.333 to 14.81
Other pre-specifiedEvaluate Median Changes in Flow Cytometric Quantification of Monocytes

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.

Time frame:
16 weeks

Results for this outcome have not been posted.

Other pre-specifiedMonocyte Transcriptome Biomarkers

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.

Time frame:
16 weeks

Results for this outcome have not been posted.

Other pre-specifiedPercent Change in Dermatology Life Quality Index (DLQI)

Calculate the percent change in Dermatology Life Quality Index (DLQI) from baseline to 16 weeks in patients.

Time frame:
16 weeks

Results for this outcome have not been posted.

Other pre-specifiedPercent Change Between Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI: PSO

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

Time frame:
16 weeks

Results for this outcome have not been posted.

Adverse events

Collected over While patients were on treatment, 16 weeks.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Apremilast for Treatment of Psoriasis With the AM-endotype0/28 (0%)0/28 (0%)13/28 (46.4%)
Most frequent other events
Showing 10 of 13
Most frequent other events
EventApremilast for Treatment of Psoriasis With the AM-endotype
NauseaGastrointestinal disorders1/28
DiarrheaGastrointestinal disorders1/28
Sinus/viral infectionInfections and infestations1/28
Arthroscopic procedureSurgical and medical procedures1/28
Contact dermatitis to watchSkin and subcutaneous tissue disorders1/28
Psoriasis flareSkin and subcutaneous tissue disorders1/28
HyponatremiaMetabolism and nutrition disorders1/28
CoughRespiratory, thoracic and mediastinal disorders1/28
COVIDInfections and infestations1/28
HeadacheGeneral disorders1/28

Baseline characteristics

Age, Continuous
Age, Continuous(years)Apremilast for Treatment of Psoriasis With the AM-endotype
Mean44.7 ± 12.6
Sex: Female, Male
Sex: Female, Male(Participants)Apremilast for Treatment of Psoriasis With the AM-endotype
Female10
Male18
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Apremilast for Treatment of Psoriasis With the AM-endotype
Hispanic or Latino0
Not Hispanic or Latino28
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Apremilast for Treatment of Psoriasis With the AM-endotype
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American5
White22
More than one race1
Unknown or Not Reported0
07

Study locations

1 site
  • University Hospitals Cleveland Medical Center
    Cleveland, Ohio 44106, United States
08

References and documents

Publications

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Study documents

  • Protocol and statistical analysis plan · May 27, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03442088
Lead sponsor
University Hospitals Cleveland Medical Center
Responsible party
Sponsor
First posted
Feb 22, 2018
Start date
Jun 1, 2018
Primary completion
Sep 30, 2021
Completion
Sep 30, 2021
Results posted
Jan 20, 2023
Last update
Jan 20, 2023

Study contacts

Kevin Cooper, MD
study chair · University Hospitals Cleveland Medical Center
Neil Korman, MD
principal investigator · University Hospitals Cleveland Medical Center

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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