NCT02425826: UNVEIL

A Phase 4 Study of Efficacy and Safety of Apremilast in Subjects With Moderate Plaque Psoriasis.

Completed Phase 4 Results posted Last updated 5 June 2023

What this trial tests

Phase 4 trial testing Apremilast in Parapsoriasis in 221 participants. Completed in 22 November 2016.

Timeline

20 April 2015

Primary endpoint
12 February 2016

22 November 2016

Quick facts

Lead sponsor	Amgen
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	221
Start date	20 April 2015
Primary completion	12 February 2016
Estimated completion	22 November 2016
Sites	26 locations across United States

Drugs / interventions tested

• Apremilast (APREMILAST) — full drug profile →
• Placebo
• Placebo-Apremilast — full drug profile →

Conditions studied

• Parapsoriasis — all drugs for Parapsoriasis →

Sponsor

Amgen — full company profile →

Who can join

18 and older, any sex, with Parapsoriasis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean Percentage Change From Baseline in the Product of BSA (%) and the sPGA Which is Considered as the Total Psoriasis Severity Index at Week 16 Primary · Baseline to Week 16 (end of phase)

BSA is a measurement of involved skin. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand (entire palmar surface or "handprint" including the fingers), which equates to approximately 1% of total body surface area. The sPGA is a 6-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), 5 (very severe) incorporating a separate assessment of the severity of the three primary signs of the plaques of all involved areas: erythema, scaling and plaque elevation with an overall sPGA calculated as (E + I + D)/3. Scores

Group	Value	95% CI
Placebo	-10.17	± 64.043
Apremilast	-48.07	± 43.699

Mean Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 16 Secondary · Baseline to Week 16 (end of phase)

DLQI is a simple, compact, and practical questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. The instrument contains ten items dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from "Very Much" (score 3) to "Not at All" or "Not relevant" (score 0). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No, scores 3 or 0 respectively), and if "No," then the p

Group	Value	95% CI
Placebo	-2.4	± 6.62
Apremilast	-4.8	± 5.80

Percentage of Participants Who Achieved a sPGA Score of Clear (0) or Almost Clear (1) at Week 16 From Baseline Secondary · Baseline to Week 16 (end of phase)

The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 6-point scale, ranging from 0 (clear) to 5 (very severe), with an overall sPGA calculated as (E + I + D)/3. Scores for each assessment are averaged and rounded to the nearest whole number to result in the final sPGA score.

Group	Value	95% CI
Placebo	9.6	4.7 – 18.5
Apremilast	30.4	23.6 – 38.2

Percentage of Participants Who Achieved a Clear (0) or Very Mild (1) on Patient Global Assessment (PtGA) Scale at Week 16 From Baseline Secondary · Baseline to Week 16 (end of phase)

The PtGA response rate is defined as the percentage of participants achieving 0 (clear) or 1 (very mild) on the PtGA scale at Week 16. The PtGA is the assessment by the participant of the overall disease severity at the time of evaluation. The PtGA is a 5-point scale ranging from 0 (clear) to 4 (severe).

Group	Value	95% CI
Placebo	20.5	12.9 – 31.2
Apremilast	33.8	26.7 – 41.7

Mean Change From Baseline in Pruritus Visual Analog Scale (VAS) Secondary · Baseline to Weeks 1 and 16 (end of phase)

The Pruritus VAS assessment was conducted at the baseline visit and each post-baseline visit. The participant was asked to place a vertical stroke on a 100 mm VAS on which the left-hand boundary (0) represents no itch, and the right-hand boundary (100) represents itch as severe as can be imagined. The distance from the mark to the left-hand boundary will be recorded. The Pruritus VAS score ranges from 0 to 100. Higher scores correspond to more severe symptom.

Week 1

Group	Value	95% CI
Placebo	-9.6	± 21.50
Apremilast	-13.9	± 20.00

Week 16

Group	Value	95% CI
Placebo	-10.2	± 30.73
Apremilast	-19.2	± 26.09

Percentage of Participants With Scalp Psoriasis Who Achieved a Clear (0) or Minimal (1) on Scalp Physician's Global Assessment (ScPGA) Scale at Week 16. Secondary · Baseline to Week 16 (end of phase)

The ScPGA assessed scalp involvement, if present at baseline. The 6-point ScPGA scale includes three dimensions (Plaque Thickening, Scaling, and Erythema) and a global assessment. Scores range from 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), to 5 (very severe). Analysis of ScPGA was restricted to the participants with scalp involvement at baseline.

Group	Value	95% CI
Placebo	38.2	26.5 – 51.4
Apremilast	50.0	40.9 – 59.1

Treatment Satisfaction Questionnaire for Medication (TSQM) Version II at Week 16 Secondary · Baseline to Week 16 (end of phase)

The TSQM version II is an 11-question self-administered instrument to understand a participation's satisfaction with the current therapy. The TSQM scale comprises four domains, on which participants evaluate their medication (i.e., effectiveness, side effects, convenience and global satisfaction. TSQM scores range from 0 to 100 for each domain; a higher score mean indicates higher satisfaction with treatment.

TSQM-Effectiveness

Group	Value	95% CI
Placebo	38.81	± 25.843
Apremilast	57.25	± 26.484

TSQM-Side Effects

Group	Value	95% CI
Placebo	75.00	± 32.428
Apremilast	78.50	± 20.858

TSQM-Convenience

Group	Value	95% CI
Placebo	65.68	± 16.650
Apremilast	66.93	± 21.216

TSQM-Global Satisfaction

Group	Value	95% CI
Placebo	48.74	± 25.673
Apremilast	63.24	± 23.624

Treatment Satisfaction Questionnaire for Medication (TSQM) Version II at Week 52 Secondary · Baseline to week 52

The TSQM version II is an 11-question self-administered instrument to understand a participants satisfaction on the current therapy. The TSQM scale comprises four domains, on which participants evaluate their medication (i.e., effectiveness, side effects, convenience and global satisfaction. TSQM scores range from 0 to 100 for each domain; a higher score indicates higher satisfaction with treatment.

TSQM-Effectiveness

Group	Value	95% CI
Placebo-Apremilast	57.68	± 26.879
Apremilast	54.13	± 26.898

TSQM-Side Effects

Group	Value	95% CI
Placebo-Apremilast	77.29	± 27.541
Apremilast	75.45	± 24.904

TSQM-Convenience

Group	Value	95% CI
Placebo-Apremilast	72.74	± 17.222
Apremilast	71.76	± 19.359

TSQM-Global Satisfaction

Group	Value	95% CI
Placebo-Apremilast	59.24	± 27.941
Apremilast	59.92	± 27.053

Mean Percentage Change From Baseline in Psoriasis Area Severity Index Score (PASI) at Week 16 Secondary · Baseline to Week 16 (end of phase)

The PASI score is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). PASI scores range from 0 to 72, with higher scores reflecting greater disease seve

Group	Value	95% CI
Placebo	-3.87	± 79.441
Apremilast	-40.72	± 49.523

Percentage of Participants Who Achieved at Least a 50% Improvement (Response) in the Psoriasis Area and Severity Index (PASI)-50 From Baseline at Week 16. Secondary · Baseline to Week 16 (end of phase)

The PASI score is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). PASI scores range from 0 to 72, with higher scores reflecting greater disease seve

Group	Value	95% CI
Placebo	24.7	16.2 – 35.6
Apremilast	53.4	45.4 – 61.2

Percentage of Participants Who Achieved at Least a 75% Improvement (Response) in the Psoriasis Area and Severity Index (PASI)-75 From Baseline at Week 16 Secondary · Baseline to Week 16 (end of phase)

The PASI score is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). PASI scores range from 0 to 72, with higher scores reflecting greater disease seve

Group	Value	95% CI
Placebo	8.2	3.8 – 16.8
Apremilast	21.6	15.8 – 28.9

Mean Percentage Change From Baseline in the Product of BSA (%) x sPGA at Week 52 Secondary · Baseline to Week 52

BSA is a measurement of involved skin. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand (entire palmar surface or "handprint" including the fingers), which equates to approximately 1% of total body surface area. The sPGA is a 6-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), 5 (very severe) incorporating a separate assessment of the severity of the three primary signs of the plaques of all involved areas: erythema, scaling and plaque elevation with an overall sPGA calculated as (E + I + D)/3. Scores

Group	Value	95% CI
Placebo-Apremilast	-42.23	± 93.211
Apremilast	-55.45	± 44.619

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events are reported for the 16-week PBO-controlled and the apremilast extension phase and monitored from the date of the first dose of apremilast to 12 January2017; maximum duration of exposure was 61.5 weeks during apremilast-exposure phase.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo-Controlled Phase: Apremilast (Weeks 0-16)

Serious: 3/147 (2%)

Deaths: —

Placebo-Controlled Phase: Placebo (Weeks 0-16)

Serious: 0/73 (0%)

Deaths: —

Extension Phase: APR/APR and Placebo/APR (Weeks 0-52)

Serious: 10/211 (5%)

Deaths: —

Serious adverse events (11 terms)

Reaction	System	Placebo-Controlled Phase: …	Placebo-Controlled Phase: …	Extension Phase: APR/APR a…
Cholelithiasis	Hepatobiliary disorders	—	—	—
Diverticulitis	Infections and infestations	—	—	—
Pneumonia	Infections and infestations	—	—	—
Pyelonephritis	Infections and infestations	—	—	—
Invasive ductal breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Keratoacanthoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Cerebrovascular accident	Nervous system disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Suicide attempt	Psychiatric disorders	—	—	—
Nephrolithiasis	Renal and urinary disorders	—	—	—
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—	—

Other adverse events (7 terms — click to expand)

Reaction	System	Placebo-Controlled Phase: …	Placebo-Controlled Phase: …	Extension Phase: APR/APR a…
Diarrhoea	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—

Most-reported serious reactions: Cholelithiasis, Diverticulitis, Pneumonia, Pyelonephritis, Invasive ductal breast carcinoma, Keratoacanthoma, Cerebrovascular accident, Dizziness.

Data from ClinicalTrials.gov NCT02425826 adverse events section.

Sponsor's own description

This study will evaluate the clinical efficacy, the patients quality of life, and safety of oral apremilast 30 mg twice daily (BID) compared to placebo, in adult patients with moderate plaque psoriasis during the 16 week Placebo controlled Phase and then upto 1 year in the Extension Phase of the trial.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
   Sbidian E, Chaimani A, Garcia-Doval I, Do G, et al · · 2017 · cited 106× · PMID 29271481 · DOI 10.1002/14651858.cd011535.pub2
2. Efficacy and Safety of Apremilast in Patients With Moderate Plaque Psoriasis With Lower BSA: Week 16 Results from the UNVEIL Study.
   Strober B, Bagel J, Lebwohl M, Stein Gold L, et al · · 2017 · cited 44× · PMID 28809995
3. Efficacy and Safety of Apremilast in Systemic- and Biologic-Naive Patients With Moderate Plaque Psoriasis: 52-Week Results of UNVEIL.
   Stein Gold L, Bagel J, Lebwohl M, Jackson JM, et al · · 2018 · cited 39× · PMID 29462231
4. Neutrophils as emerging protagonists and targets in chronic inflammatory diseases.
   Rawat K, Shrivastava A. · · 2022 · cited 35× · PMID 36289077 · DOI 10.1007/s00011-022-01627-6
5. Apremilast Long-Term Safety Up to 5 Years from 15 Pooled Randomized, Placebo-Controlled Studies of Psoriasis, Psoriatic Arthritis, and Behçet's Syndrome.
   Mease PJ, Hatemi G, Paris M, Cheng S, et al · · 2023 · cited 31× · PMID 37316690 · DOI 10.1007/s40257-023-00783-7
6. Phosphodiesterase-4 Inhibition in the Management of Psoriasis.
   Crowley EL, Gooderham MJ. · · 2023 · cited 24× · PMID 38258034 · DOI 10.3390/pharmaceutics16010023
7. Oral small-molecule tyrosine kinase 2 and phosphodiesterase 4 inhibitors in plaque psoriasis: a network meta-analysis.
   Xu Y, Li Z, Wu S, Guo L, et al · · 2023 · cited 11× · PMID 37334353 · DOI 10.3389/fimmu.2023.1180170
8. Effect of baseline disease severity on achievement of treatment target with apremilast: results from a pooled analysis.
   Reich K, Mrowietz U, Menter A, Griffiths CEM, et al · · 2021 · cited 9× · PMID 34255891 · DOI 10.1111/jdv.17520