NCT00773734

Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate-to-Severe Plaque-Type Psoriasis (Core Study)

Completed Phase 2 Results posted Last updated 7 May 2020

What this trial tests

Phase 2 trial testing Apremilast 10mg in Psoriasis in 352 participants. Completed in 20 May 2015.

Timeline

1 September 2008

Primary endpoint
1 August 2009

20 May 2015

Quick facts

Lead sponsor	Amgen
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	352
Start date	1 September 2008
Primary completion	1 August 2009
Estimated completion	20 May 2015
Sites	35 locations across Canada, United States

Drugs / interventions tested

• Apremilast 10mg — full drug profile →
• Apremilast 20mg — full drug profile →
• Apremilast 30 mg — full drug profile →
• Placebo
• Apremilast 30mg — full drug profile →
• Apremilast 20mg — full drug profile →

Conditions studied

• Psoriasis — all drugs for Psoriasis →
• Plaque-type Psoriasis — all drugs for Plaque-type Psoriasis →

Sponsor

Amgen — full company profile →

Who can join

18 and older, any sex, with Psoriasis or Plaque-type 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.

Core Study: Percentage of Participants Who Achieved a 75% Improvement (Response) in Psoriasis Area and Severity Index (PASI) at Week 16 Primary · Week 0 and Week 16

PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI was 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. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) o

Group	Value	95% CI
Placebo BID	5.7
Apremilast 10mg BID	11.2
Apremilast 20mg BID	28.7
Apremilast 30 mg BID	40.9

Core Study: Percentage of Participants Who Achieved a 75% Improvement (Response) in PASI Score at Week 24 Secondary · Week 0 to Week 24

PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 24. The improvement in PASI score was used as a measure of efficacy.The PASI was 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. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on

Group	Value	95% CI
Apremilast 10mg BID	18.0	10.6 – 27.5
Apremilast 20mg BID	26.4	17.6 – 37.0
Apremilast 30 mg BID	39.8	29.5 – 50.8
PBO-Apremilast 20mg BID	41.2	24.6 – 59.3
PBO-Apremilast 30 mg BID	44.4	27.9 – 61.9

Core Study: Percentage of Participants Who Achieved a 50% Improvement (Response) in PASI Score at Week 16 Secondary · Week 0 to Week 16

PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy The PASI score was 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. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very sev

Group	Value	95% CI
Placebo BID	25.0
Apremilast 10mg BID	38.2
Apremilast 20mg BID	47.1
Apremilast 30 mg BID	60.2

Core Study: Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score at Week 24 Secondary · Week 0 to Week 24

PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 24. The improvement in PASI score was used as a measure of efficacy. The PASI score was 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. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very se

Group	Value	95% CI
Apremilast 10mg BID	38.2	28.1 – 49.1
Apremilast 20mg	49.4	38.5 – 60.4
Apremilast 30 mg BID	65.9	55.0 – 75.7
Placebo-Apremilast 20mg BID	61.8	43.6 – 77.8
PBO-Apremilast 30 mg BID	75.0	57.8 – 87.9

Core Study: Percentage of Participants Who Achieved a 90% Improvement (Response) From Baseline in the PASI Score at Week 16 Secondary · Week 0 to Week 16

PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI score was 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. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very se

Group	Value	95% CI
Placebo BID	1.1
Apremilast 10mg BID	4.5
Apremilast 20mg BID	9.2
Apremilast 30 mg BID	11.4

Core Study: Percentage of Participants Who Achieved a 90% Improvement (Response) in the PASI Score at Week 24 Secondary · Week 0 to Week 24

PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 24. The improvement in PASI score was used as a measure of efficacy..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. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were scored on a scale of 0 (none) to 4 (very severe)

Group	Value	95% CI
Apremilast 10mg	4.5	1.2 – 11.1
Apremilast 20mg	8.0	3.3 – 15.9
Apremilast 30 mg	14.8	8.1 – 23.9
PBO-Apremilast 20mg BID	14.7	5.0 – 31.1
Placebo-Apremilast 30 mg BID	16.7	6.4 – 32.8

Core Study: Percent Change From Baseline in PASI Score at Week 16 Secondary · Week 0 to Week 16

The PASI was 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. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were 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 was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement

Group	Value	95% CI
Placebo BID	-20.3	± 3.98
Apremilast 10mg BID	-34.0	± 4.00
Apremilast 20mg BID	-45.4	± 4.12
Apremilast 30 mg BID	-53.2	± 4.00

Core Study: Percent Change From Baseline in PASI Score at Week 24 Secondary · Week 0 to Week 24

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. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were 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 was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement)

Group	Value	95% CI
Apremilast 10mg BID	-36.3	± 36.03
Apremilast 20mg BID	-46.5	± 36.08
Apremilast 30 mg BID	-56.8	± 34.99
PBO-Apremilast 20mg BID	-61.7	± 25.35
PBO-Apremilast 30 mg BID	-61.7	± 32.67

Core Study: Percentage of Participants With a Static Physician Global Assessment (sPGA) Greater Than 2 at Baseline Who Achieved a Score of 0 or 1 at Week 16 Secondary · Week 0 to Week 16

The sPGA was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA was a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling). The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling . Scores for thickness, erythema and scaling are then summed and the mean of

Group	Value	95% CI
Placebo	12.6
Apremilast 10mg	10.5
Apremilast 20mg	25.0
Apremilast 30 mg	33.7

Core Study: Percentage of Participants Who Achieved a Static Physician Global Assessment (sPGA) Score of 0 or 1 at Week 24 Secondary · Week 0 and Week 24

The sPGA was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA was a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling). The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling . Scores for thickness, erythema and scaling are then summed and the mean of

Group	Value	95% CI
Apremilast 10mg BID	13.5	7.2 – 22.4
Apremilast 20mg BID	24.1	15.6 – 34.5
Apremilast 30 mg BID	34.1	24.3 – 45.0
Placebo-Apremilast 20 mg BID	41.2	24.6 – 59.3
Placebo-Apremilast 30 mg BID	50.0	32.9 – 67.1

Core Study: Percent Change From Baseline in the Percent of Affected Body Surface Area (BSA) During the Placebo Controlled Phase Secondary · Week 0 to Week 16

The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or "handprint"), which equates to approximately 1% of total BSA.

Group	Value	95% CI
Placebo BID	-8.0	± 4.58
Apremilast 10mg BID	-28.3	± 4.60
Apremilast 20mg BID	-38.0	± 4.74
Apremilast 30 mg BID	-50.4	± 4.63

Core Study: Percent Change From Baseline in the Percent of Affected Body Surface Area (BSA) During the Active Treatment Phase at Week 24 Secondary · Week 0 to Week 24

The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or "handprint"), which equates to approximately 1% of total BSA.

Group	Value	95% CI
Apremilast 10mg BID	-28.1	± 46.78
Apremilast 20mg BID	-40.6	± 43.71
Apremilast 30 mg BID	-54.0	± 37.32
Placebo-Apremilast 20 mg BID	-52.5	± 37.35
Placebo-Apremilast 30 mg BID	-54.2	± 42.08

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events are reported for the 16-week placebo-controlled phase and up to the LTE period, (6 years) for all participants who were randomized or re-randomized to apremilast at any time during the core, the extension or the long term extension study.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo (Weeks 0-16)

Serious: 2/88 (2%)

Deaths: —

Apremilast 10mg BID (Weeks 0-16)

Serious: 0/89 (0%)

Deaths: —

Apremilast 20mg BID (Weeks 0-16)

Serious: 3/87 (3%)

Deaths: —

Apremilast 30mg BID (Weeks 0-16)

Serious: 4/88 (5%)

Deaths: —

Apremilast 10mg BID (APR Exposure Period) Years 0-6

Serious: 2/89 (2%)

Deaths: —

Apremilast 20mg BID (APR Exposure Period) Years 0-6

Serious: 9/121 (7%)

Deaths: —

Apremilast 30mg BID (APR Exposure Period) Years 0-6

Serious: 9/124 (7%)

Deaths: —

Serious adverse events (27 terms)

Reaction	System	Placebo (Weeks 0-16)	Apremilast 10mg BID (Weeks…	Apremilast 20mg BID (Weeks…	Apremilast 30mg BID (Weeks…	Apremilast 10mg BID (APR E…	Apremilast 20mg BID (APR E…	Apremilast 30mg BID (APR E…
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—
Pregnancy	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—	—
Angina pectoris	Cardiac disorders	—	—	—	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—	—	—	—
Pancreatitis	Gastrointestinal disorders	—	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—	—
Sudden death	General disorders	—	—	—	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—
Ankle fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Meniscus lesion	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Tibia fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Compartment syndrome	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Muscle haemorrhage	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—	—	—	—
Nephrolithiasis	Renal and urinary disorders	—	—	—	—	—	—	—
Benign prostatic hyperplasia	Reproductive system and breast disorders	—	—	—	—	—	—	—
Epididymitis	Reproductive system and breast disorders	—	—	—	—	—	—	—
Asthma	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Drug eruption	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—

Other adverse events (13 terms — click to expand)

Reaction	System	Placebo (Weeks 0-16)	Apremilast 10mg BID (Weeks…	Apremilast 20mg BID (Weeks…	Apremilast 30mg BID (Weeks…	Apremilast 10mg BID (APR E…	Apremilast 20mg BID (APR E…	Apremilast 30mg BID (APR E…
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—
Tension headache	Nervous system disorders	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—	—
Viral upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—	—	—	—
Muscle strain	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Sinusitis	Infections and infestations	—	—	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—

Most-reported serious reactions: Prostate cancer, Pregnancy, Angina pectoris, Myocardial infarction, Pancreatitis, Oedema peripheral, Sudden death, Bronchitis.

Data from ClinicalTrials.gov NCT00773734 adverse events section.

Sponsor's own description

The purpose of this study was to test if the drug apremilast was safe, if it helped improve psoriasis, and how well the participants tolerated it.

Publications & conference data

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

1. Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial.
   Papp K, Cather JC, Rosoph L, Sofen H, et al · · 2012 · cited 191× · PMID 22748702 · DOI 10.1016/s0140-6736(12)60642-4
2. 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
3. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
   Sbidian E, Chaimani A, Garcia-Doval I, Doney L, et al · · 2022 · cited 84× · PMID 35603936 · DOI 10.1002/14651858.cd011535.pub5
4. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
   Sbidian E, Chaimani A, Afach S, Doney L, et al · · 2020 · cited 78× · PMID 31917873 · DOI 10.1002/14651858.cd011535.pub3
5. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
   Sbidian E, Chaimani A, Guelimi R, Garcia-Doval I, et al · · 2023 · cited 67× · PMID 37436070 · DOI 10.1002/14651858.cd011535.pub6
6. PDE4 Inhibition and Inflammatory Bowel Disease: A Novel Therapeutic Avenue.
   Spadaccini M, D'Alessio S, Peyrin-Biroulet L, Danese S. · · 2017 · cited 55× · PMID 28617319 · DOI 10.3390/ijms18061276
7. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
   Sbidian E, Chaimani A, Garcia-Doval I, Doney L, et al · · 2021 · cited 54× · PMID 33871055 · DOI 10.1002/14651858.cd011535.pub4
8. Improvements in patient-reported outcomes with apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of moderate to severe psoriasis: results from a phase IIb randomized, controlled study.
   Strand V, Fiorentino D, Hu C, Day RM, et al · · 2013 · cited 52× · PMID 23663752 · DOI 10.1186/1477-7525-11-82