Trial Outcomes & Findings for Monocyte Biomarkers in Moderate to Severe Plaque Psoriasis Subjects Treated With Apremilast (NCT NCT03442088)

NCT ID: NCT03442088

Last Updated: 2023-01-20

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

Baseline, Week 16

Results posted on

2023-01-20

Participant Flow

Participant milestones

Participant milestones
Measure
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. Apremilast: Apremilast will be given as approved by the FDA for the treatment of moderate to severe plaque psoriasis. An initial dose titration from Day 1 (10mg) to Day 5 (30mg). Following titration, the recommended maintenance dosage of 30 mg twice daily taken orally starting on Day 6 will be dispensed, as per labeled indication.
Overall Study
STARTED
28
Overall Study
COMPLETED
23
Overall Study
NOT COMPLETED
5

Reasons for withdrawal

Reasons for withdrawal
Measure
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. Apremilast: Apremilast will be given as approved by the FDA for the treatment of moderate to severe plaque psoriasis. An initial dose titration from Day 1 (10mg) to Day 5 (30mg). Following titration, the recommended maintenance dosage of 30 mg twice daily taken orally starting on Day 6 will be dispensed, as per labeled indication.
Overall Study
Adverse Event
1
Overall Study
Lack of Efficacy
2
Overall Study
Lost to Follow-up
2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Apremilast for Treatment of Psoriasis With the AM-endotype
n=28 Participants
Psoriasis patients with the AM-endotype will be followed during treatment over 16 weeks with 5 monthly individual blood draws will be enrolled. Apremilast: Apremilast will be given as approved by the FDA for the treatment of moderate to severe plaque psoriasis. An initial dose titration from Day 1 (10mg) to Day 5 (30mg). Following titration, the recommended maintenance dosage of 30 mg twice daily taken orally starting on Day 6 will be dispensed, as per labeled indication.
Age, Continuous
44.7 years
STANDARD_DEVIATION 12.6 • n=99 Participants
Sex: Female, Male
Female
10 Participants
n=99 Participants
Sex: Female, Male
Male
18 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
28 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=99 Participants
Race (NIH/OMB)
Asian
0 Participants
n=99 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=99 Participants
Race (NIH/OMB)
Black or African American
5 Participants
n=99 Participants
Race (NIH/OMB)
White
22 Participants
n=99 Participants
Race (NIH/OMB)
More than one race
1 Participants
n=99 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants

PRIMARY outcome

Timeframe: Baseline, Week 16

Population: 1 subject missed interim visits, so data was not analyzed for this one participant.

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.

Outcome measures

Outcome measures
Measure
Apremilast for Treatment of Psoriasis With the AM-endotype
n=22 Participants
Psoriasis patients with the AM-endotype will be followed during treatment over 16 weeks with 5 monthly individual blood draws will be enrolled. Apremilast: Apremilast will be given as approved by the FDA for the treatment of moderate to severe plaque psoriasis. An initial dose titration from Day 1 (10mg) to Day 5 (30mg). Following titration, the recommended maintenance dosage of 30 mg twice daily taken orally starting on Day 6 will be dispensed, as per labeled indication.
The Primary Outcome Measure Will be to Evaluate Change in Aberrant Inflammatory Profiles of Activated Blood Monocytes (Aberrant-monocyte Endotype Patients (AM-endotype).
Baseline
0.5665 Percent change
Standard Deviation 0.5135
The Primary Outcome Measure Will be to Evaluate Change in Aberrant Inflammatory Profiles of Activated Blood Monocytes (Aberrant-monocyte Endotype Patients (AM-endotype).
Week 16
0.1715 Percent change
Standard Deviation 0.2635

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Analysis was only done on participants had complete data sets including sequencing.

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

Outcome measures

Outcome measures
Measure
Apremilast for Treatment of Psoriasis With the AM-endotype
n=17 Participants
Psoriasis patients with the AM-endotype will be followed during treatment over 16 weeks with 5 monthly individual blood draws will be enrolled. Apremilast: Apremilast will be given as approved by the FDA for the treatment of moderate to severe plaque psoriasis. An initial dose titration from Day 1 (10mg) to Day 5 (30mg). Following titration, the recommended maintenance dosage of 30 mg twice daily taken orally starting on Day 6 will be dispensed, as per labeled indication.
Change in Serum Myeloperoxidase
Baseline
24198 Pg/mL
Standard Deviation 3835
Change in Serum Myeloperoxidase
Week 16
24294 Pg/mL
Standard Deviation 4722

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Analysis was only done on participants had complete data sets including sequencing.

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

Outcome measures

Outcome measures
Measure
Apremilast for Treatment of Psoriasis With the AM-endotype
n=17 Participants
Psoriasis patients with the AM-endotype will be followed during treatment over 16 weeks with 5 monthly individual blood draws will be enrolled. Apremilast: Apremilast will be given as approved by the FDA for the treatment of moderate to severe plaque psoriasis. An initial dose titration from Day 1 (10mg) to Day 5 (30mg). Following titration, the recommended maintenance dosage of 30 mg twice daily taken orally starting on Day 6 will be dispensed, as per labeled indication.
Change in TNF Alpha
Baseline
14.95 Pg/mL
Standard Deviation 4.017
Change in TNF Alpha
Week 16
14.26 Pg/mL
Standard Deviation 3.383

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Analysis was only done on participants had complete data sets including sequencing.

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

Outcome measures

Outcome measures
Measure
Apremilast for Treatment of Psoriasis With the AM-endotype
n=17 Participants
Psoriasis patients with the AM-endotype will be followed during treatment over 16 weeks with 5 monthly individual blood draws will be enrolled. Apremilast: Apremilast will be given as approved by the FDA for the treatment of moderate to severe plaque psoriasis. An initial dose titration from Day 1 (10mg) to Day 5 (30mg). Following titration, the recommended maintenance dosage of 30 mg twice daily taken orally starting on Day 6 will be dispensed, as per labeled indication.
Change in IL-17
Baseline
1.513 Pg/mL
Standard Deviation 5.76
Change in IL-17
Week 16
-0.8315 Pg/mL
Standard Deviation 5.824

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Analysis was only done on participants had complete data sets including sequencing.

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

Outcome measures

Outcome measures
Measure
Apremilast for Treatment of Psoriasis With the AM-endotype
n=17 Participants
Psoriasis patients with the AM-endotype will be followed during treatment over 16 weeks with 5 monthly individual blood draws will be enrolled. Apremilast: Apremilast will be given as approved by the FDA for the treatment of moderate to severe plaque psoriasis. An initial dose titration from Day 1 (10mg) to Day 5 (30mg). Following titration, the recommended maintenance dosage of 30 mg twice daily taken orally starting on Day 6 will be dispensed, as per labeled indication.
Change in Tissue Factor
Week 16
75.52 Pg/mL
Standard Deviation 28.03
Change in Tissue Factor
Baseline
72.28 Pg/mL
Standard Deviation 23.72

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 16 weeks

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

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Outcome measures

Outcome data not reported

Adverse Events

Apremilast for Treatment of Psoriasis With the AM-endotype

Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Apremilast for Treatment of Psoriasis With the AM-endotype
n=28 participants at risk
Psoriasis patients with the AM-endotype will be followed during treatment over 16 weeks with 5 monthly individual blood draws will be enrolled. Apremilast: Apremilast will be given as approved by the FDA for the treatment of moderate to severe plaque psoriasis. An initial dose titration from Day 1 (10mg) to Day 5 (30mg). Following titration, the recommended maintenance dosage of 30 mg twice daily taken orally starting on Day 6 will be dispensed, as per labeled indication.
Gastrointestinal disorders
Nausea
3.6%
1/28 • Number of events 5 • While patients were on treatment, 16 weeks.
Gastrointestinal disorders
Diarrhea
3.6%
1/28 • Number of events 6 • While patients were on treatment, 16 weeks.
Infections and infestations
Sinus/viral infection
3.6%
1/28 • Number of events 3 • While patients were on treatment, 16 weeks.
Surgical and medical procedures
Arthroscopic procedure
3.6%
1/28 • Number of events 1 • While patients were on treatment, 16 weeks.
Skin and subcutaneous tissue disorders
Contact dermatitis to watch
3.6%
1/28 • Number of events 1 • While patients were on treatment, 16 weeks.
Skin and subcutaneous tissue disorders
Psoriasis flare
3.6%
1/28 • Number of events 3 • While patients were on treatment, 16 weeks.
Metabolism and nutrition disorders
Hyponatremia
3.6%
1/28 • Number of events 1 • While patients were on treatment, 16 weeks.
Respiratory, thoracic and mediastinal disorders
Cough
3.6%
1/28 • Number of events 2 • While patients were on treatment, 16 weeks.
Infections and infestations
COVID
3.6%
1/28 • Number of events 1 • While patients were on treatment, 16 weeks.
General disorders
Headache
3.6%
1/28 • Number of events 2 • While patients were on treatment, 16 weeks.
Musculoskeletal and connective tissue disorders
Muscle spasm
3.6%
1/28 • Number of events 1 • While patients were on treatment, 16 weeks.
Musculoskeletal and connective tissue disorders
Sprained ankle
3.6%
1/28 • Number of events 1 • While patients were on treatment, 16 weeks.
Skin and subcutaneous tissue disorders
Itchiness
3.6%
1/28 • Number of events 1 • While patients were on treatment, 16 weeks.

Additional Information

Dr. Neil Korman, Director Clinical Trials Unit

University Hospitals Cleveland Medical Center

Phone: 216-844-8200

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place