NCT03721172: ADVANCE

Apremilast as a Direct Treatment for Mild-to-moderate Plaque Psoriasis Versus Placebo: an Analysis of Clinical Safety and Efficacy

Completed Phase 3 Results posted Last updated 29 May 2024

What this trial tests

Phase 3 trial testing Apremilast in Psoriasis in 595 participants. Completed in 24 July 2020.

Timeline

11 March 2019

Primary endpoint
6 March 2020

24 July 2020

Quick facts

Lead sponsor	Amgen
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	595
Start date	11 March 2019
Primary completion	6 March 2020
Estimated completion	24 July 2020
Sites	64 locations across Canada, United States

Drugs / interventions tested

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

Conditions studied

• Psoriasis — all drugs for Psoriasis →

Sponsor

Amgen — full company profile →

Who can join

18 and older, any sex, with Psoriasis. 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.

Percentage of Participants With a Static Physician Global Assessment (sPGA) Response at Week 16 During the Placebo-Controlled Phase Primary · Baseline and Week 16 of the placebo-controlled phase

The sPGA is a 5-point scale where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, and 4 =severe. Scores incorporate an assessment by the Investigator of the severity of the 3 primary signs of the disease: erythema, scaling and plaque elevation. An sPGA response is defined as sPGA score of clear (0) or almost clear (1) and with at least a 2-point reduction from baseline at Week 16.

Group	Value	95% CI
Placebo-controlled Phase: Placebo	4.1	1.8 – 6.4
Placebo-controlled Phase: Apremilast 30 mg	21.6	16.7 – 26.4

Percentage of Participants With a ≥ 75 Percent (%) Improvement From Baseline in Affected Body Surface Area (BSA) at Week 16 Secondary · Baseline and Week 16 of the placebo-controlled phase

The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or "handprints" (each entire palmar surface or "handprint" equates to approximately 1% of total body surface area).

Group	Value	95% CI
Placebo-controlled Phase: Placebo	7.4	4.2 – 10.6
Placebo-controlled Phase: Apremilast 30 mg	33.0	27.4 – 38.6

Change From Baseline in Percentage of Affected BSA at Week 16 Secondary · Baseline and Week 16 of the placebo-controlled phase

The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or "handprints" (each entire palmar surface or "handprint" equates to approximately 1% of total body surface area). A negative change from baseline indicates a reduction of affected BSA.

Group	Value	95% CI
Placebo-controlled Phase: Placebo	-0.07	± 0.24
Placebo-controlled Phase: Apremilast 30 mg	-3.45	± 0.24

Change From Baseline in Total Psoriasis Area Severity Index (PASI) Score at Week 16 Secondary · Baseline and Week 16 of the placebo-controlled phase

The PASI 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). The total qualitative score (sum of erythema, thickness, and scaling scores) is multipli

Group	Value	95% CI
Placebo-controlled Phase: Placebo	-0.54	± 0.20
Placebo-controlled Phase: Apremilast 30 mg	-3.47	± 0.20

Percentage of Participants Who Achieved BSA ≤ 3% for Participants With Baseline Affected BSA > 3% at Week 16 Secondary · Baseline and Week 16 of the placebo-controlled phase

The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or "handprints" (each entire palmar surface or "handprint" equates to approximately 1% of total body surface area).

Group	Value	95% CI
Placebo-controlled Phase: Placebo	22.9	17.4 – 28.4
Placebo-controlled Phase: Apremilast 30 mg	61.0	54.6 – 67.3

Percentage of Participants With ≥ 4-point Reduction From Baseline in Whole Body Itch Numeric Rating Scale (NRS) Score at Week 16 Who Had Baseline Whole Body Itch NRS ≥ 4 Secondary · Baseline and Week 16 of the placebo-controlled phase

The whole body itch NRS is a self-reported measure where participants were asked to assess whole body itch and select a number on a scale of 0-10, where 0 represents no itch, and 10 represents the worst imaginable itch. A reduction in score from baseline represents an improvement in symptoms.

Group	Value	95% CI
Placebo-controlled Phase: Placebo	18.6	13.4 – 23.7
Placebo-controlled Phase: Apremilast 30 mg	43.2	36.9 – 49.5

Percentage of Participants With a Scalp Physician Global Assessment (ScPGA) Response at Week 16 Among Participants With Baseline scPGA Score ≥ 2 at Week 16 Secondary · Baseline and Week 16 of the placebo-controlled phase

The ScPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), incorporating an Investigator's assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation of the overall scalp. An ScPGA response is defined as and ScPGA score clear (0) or almost clear (1) with at least a 2-point reduction from baseline among participants with a baseline ScPGA score ≥ 2.

Group	Value	95% CI
Placebo-controlled Phase: Placebo	16.6	11.1 – 22.2
Placebo-controlled Phase: Apremilast 30 mg	44.0	37.1 – 51.0

Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 16 Secondary · Baseline and Week 16 of the placebo-controlled phase

The DLQI is a 10 item questionnaire dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from 0 (not at all) to 3 (very much). 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), and if "No," then the subject is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being 0 (not at all), 1 (a little) and 2 (a lot). Total scores have a possible range of 0 to 30,

Group	Value	95% CI
Placebo-controlled Phase: Placebo	-2.4	± 0.3
Placebo-controlled Phase: Apremilast 30 mg	-5.2	± 0.3

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Secondary · Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up)

An adverse event (AE) is An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A TEAE is any AE that occurs following administration of study treatment. Frequency of TEAEs was assessed as well as severity and treatment relatedness. A TEAE was considered severe based on the Investigator's assessment. A TEAE could be severe if it was serious or non-serious, had symptoms causing discomfort or pain, requiring medical or surgical attention or intervention, interfered with activities of daily life and if drug thera

Any TEAE

Group	Value	95% CI
Placebo-controlled Phase: Placebo	139
Placebo-controlled Phase: Apremilast 30 mg	195
Apremalist: Placebo-controlled Phase and Extension Phase	351

Severe TEAE

Group	Value	95% CI
Placebo-controlled Phase: Placebo	2
Placebo-controlled Phase: Apremilast 30 mg	8
Apremalist: Placebo-controlled Phase and Extension Phase	24

Treatment-related TEAE

Group	Value	95% CI
Placebo-controlled Phase: Placebo	36
Placebo-controlled Phase: Apremilast 30 mg	110
Apremalist: Placebo-controlled Phase and Extension Phase	186

Adverse events — posted to ClinicalTrials.gov

Time frame: Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo-controlled Phase: Placebo

Serious: 4/296 (1%)

Deaths: 0/296

Placebo-controlled Phase: Apremilast 30 mg

Serious: 1/298 (0%)

Deaths: 0/298

Apremalist: Placebo-controlled Phase and Extension Phase

Serious: 12/544 (2%)

Deaths: 0/544

Serious adverse events (17 terms)

Reaction	System	Placebo-controlled Phase: …	Placebo-controlled Phase: …	Apremalist: Placebo-contro…
Pneumonia	Infections and infestations	—	—	—
Angina pectoris	Cardiac disorders	—	—	—
Cardiac failure	Cardiac disorders	—	—	—
Cardiac failure congestive	Cardiac disorders	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—
Myocardial ischaemia	Cardiac disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Intestinal perforation	Gastrointestinal disorders	—	—	—
Oral disorder	Gastrointestinal disorders	—	—	—
Pancreatitis acute	Gastrointestinal disorders	—	—	—
Cellulitis	Infections and infestations	—	—	—
Pneumonia pneumococcal	Infections and infestations	—	—	—
Post procedural complication	Injury, poisoning and procedural complications	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Migraine without aura	Nervous system disorders	—	—	—
Ectopic pregnancy	Pregnancy, puerperium and perinatal conditions	—	—	—

Other adverse events (5 terms — click to expand)

Reaction	System	Placebo-controlled Phase: …	Placebo-controlled Phase: …	Apremalist: Placebo-contro…
Diarrhoea	Gastrointestinal disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—

Most-reported serious reactions: Pneumonia, Angina pectoris, Cardiac failure, Cardiac failure congestive, Myocardial infarction, Myocardial ischaemia, Abdominal pain, Intestinal perforation.

Data from ClinicalTrials.gov NCT03721172 adverse events section.

Sponsor's own description

This is a Phase 3, multicenter, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy and safety of apremilast (CC-10004) in subjects with mild to moderate plaque psoriasis.

Approximately 574 subjects with mild to moderate plaque psoriasis will be randomized 1:1 to receive either apremilast 30 mg BID or placebo for the first 16 weeks.

Publications & conference data

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

1. An Overview of PDE4 Inhibitors in Clinical Trials: 2010 to Early 2022.
   Crocetti L, Floresta G, Cilibrizzi A, Giovannoni MP. · · 2022 · cited 85× · PMID 35956914 · DOI 10.3390/molecules27154964
2. Molecular and Cellular Mechanisms of Itch in Psoriasis.
   Komiya E, Tominaga M, Kamata Y, Suga Y, et al · · 2020 · cited 66× · PMID 33182442 · DOI 10.3390/ijms21218406
3. Efficacy and safety of apremilast in patients with mild-to-moderate plaque psoriasis: Results of a phase 3, multicenter, randomized, double-blind, placebo-controlled trial.
   Stein Gold L, Papp K, Pariser D, Green L, et al · · 2022 · cited 41× · PMID 34343599 · DOI 10.1016/j.jaad.2021.07.040
4. 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
5. A New Generation of Treatments for Itch.
   Fowler E, Yosipovitch G. · · 2020 · cited 30× · PMID 31940047 · DOI 10.2340/00015555-3347
6. Phosphodiesterase-4 Inhibition in the Management of Psoriasis.
   Crowley EL, Gooderham MJ. · · 2023 · cited 24× · PMID 38258034 · DOI 10.3390/pharmaceutics16010023
7. Targeting neutrophils for cancer therapy.
   Kwak JW, Houghton AM. · · 2025 · cited 11× · PMID 40374764 · DOI 10.1038/s41573-025-01210-8
8. 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