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NCT01212770: PALACE 3

PALACE 3: Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis

Completed Phase 3 Results posted Last updated 6 May 2020
What this trial tests

Phase 3 trial testing Apremilast 20mg in Psoriatic Arthritis in 505 participants. Completed in 9 February 2017.

Timeline
30 September 2010
Primary endpoint
21 August 2012
9 February 2017

Quick facts

Lead sponsorAmgen
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment505
Start date30 September 2010
Primary completion21 August 2012
Estimated completion9 February 2017
Sites91 locations across France, Italy, Finland, Russia, Slovakia, United Kingdom, Germany, Poland

Drugs / interventions tested

Conditions studied

Sponsor

Amgen — full company profile →

Who can join

18 and older, any sex, with Psoriatic Arthritis. 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 an American College of Rheumatology 20% (ACR20) Response at Week 16 Primary · Baseline and Week 16

Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient

GroupValue95% CI
Placebo18.3
Apremilast 20 mg28.4
Apremilast 30 mg40.7
Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 16 Secondary · Baseline and Week 16

The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe,

GroupValue95% CI
Placebo-0.065± 0.0335
Apremilast 20 mg-0.131± 0.0337
Apremilast 30 mg-0.192± 0.0339
Percentage of Participants With an ACR 20 Response at Week 24 Secondary · Baseline and Week 24

Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient

GroupValue95% CI
Placebo15.4
Apremilast 20 mg26.6
Apremilast 30 mg31.1
Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 24 Secondary · Baseline and Week 24

The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe,

GroupValue95% CI
Placebo-0.053± 0.0350
Apremilast 20 mg-0.137± 0.0351
Apremilast 30 mg-0.192± 0.0353
Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16 Secondary · Baseline and Week 16

The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of heal

GroupValue95% CI
Placebo1.14± 0.589
Apremilast 20 mg2.29± 0.592
Apremilast 30 mg3.47± 0.594
Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16 Secondary · Baseline and Week 16

Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as dec

GroupValue95% CI
Placebo27.2
Apremilast 20 mg37.9
Apremilast 30 mg52.7
Percentage of Participants Achieving a ≥ 75% Improvement in Psoriasis Area and Severity Index Score (PASI75) at Week 16 Secondary · Baseline and Week 16

The percentage of participants with Baseline psoriasis body surface area (BSA) involvement ≥ 3% who achieved 75% or greater improvement from Baseline in Psoriasis Area and Severity Index (PASI) score after 16 weeks of treatment. The Psoriasis Area and Severity Index (PASI) score is a combination of the intensity of psoriasis, assessed by erythema (reddening), induration (plaque thickness) and desquamation (scaling) scored on a scale from 0 (none) to 4 (very severe), together with the percentage of the area affected, rated on a scale from 0 (no involvement) to 6 (90% to 100% involvement). PASI

GroupValue95% CI
Placebo7.9
Apremilast 20 mg20.9
Apremilast 30 mg22.2
Change From Baseline in Patient's Assessment of Pain at Week 16 Secondary · Baseline and Week 16

The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.

GroupValue95% CI
Placebo-4.9± 1.79
Apremilast 20 mg-8.6± 1.80
Apremilast 30 mg-12.7± 1.81
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16 Secondary · Baseline and Week 16

The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses.

GroupValue95% CI
Placebo-0.7± 0.27
Apremilast 20 mg-0.7± 0.29
Apremilast 30 mg-1.0± 0.27
Change From Baseline in Dactylitis Severity Score at Week 16 Secondary · Baseline and Week 16

Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.

GroupValue95% CI
Placebo-1.3± 0.34
Apremilast 20 mg-1.7± 0.33
Apremilast 30 mg-2.1± 0.32
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16 Secondary · Baseline and Week 16

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been define

GroupValue95% CI
Placebo-2.76± 0.869
Apremilast 20 mg-4.61± 0.886
Apremilast 30 mg-7.70± 0.881
Change From Baseline in the Disease Activity Score (DAS28) at Week 16 Secondary · Baseline and Week 16

The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 sc

GroupValue95% CI
Placebo-0.28± 0.084
Apremilast 20 mg-0.54± 0.085
Apremilast 30 mg-0.74± 0.085

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs are reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants and reported for the Apremilast Exposure Period from Week 0 to Week 260; median duration of apremilast 20 mg BID was 121.71 weeks and 232.50 weeks for apremilast 30 mg twice daily. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Weeks 0-24: Placebo (Placebo-Controlled Phase)
Serious: 9/168 (5%)
Deaths:
Weeks 0-24: Apremilast 20 mg (Placebo- Controlled Phase)
Serious: 4/170 (2%)
Deaths:
Weeks 0-24: Apremilast 30 mg (Placebo- Controlled Phase)
Serious: 6/167 (4%)
Deaths:
APR Exposure Period Up to 5 Years: Apremilast 20 mg
Serious: 38/241 (16%)
Deaths:
APR Exposure Period Up to 5 Years: Apremilast 20mg/30 mg
Serious: 4/97 (4%)
Deaths:
APR Exposure Period Up to 5 Years: Apremilast 30 mg
Serious: 54/242 (22%)
Deaths:

Serious adverse events (110 terms)

ReactionSystemWeeks 0-24: Placebo (Place…Weeks 0-24: Apremilast 20 …Weeks 0-24: Apremilast 30 …APR Exposure Period Up to …APR Exposure Period Up to …APR Exposure Period Up to …
Psoriatic arthropathyMusculoskeletal and connective tissue disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
Angina unstableCardiac disorders
Pancreatitis acuteGastrointestinal disorders
PneumoniaInfections and infestations
Suicidal ideationPsychiatric disorders
HypertensionVascular disorders
AnaemiaBlood and lymphatic system disorders
Acute myocardial infarctionCardiac disorders
Angina pectorisCardiac disorders
Atrial fibrillationCardiac disorders
Atrioventricular block completeCardiac disorders
Cardiac failureCardiac disorders
Coronary artery diseaseCardiac disorders
Myocardial infarctionCardiac disorders
Myocardial ischaemiaCardiac disorders
Sick sinus syndromeCardiac disorders
Supraventricular tachycardiaCardiac disorders
Arteriovenous malformationCongenital, familial and genetic disorders
Pulmonary arteriovenous fistulaCongenital, familial and genetic disorders
Meniere's diseaseEar and labyrinth disorders
AcromegalyEndocrine disorders
Abdominal herniaGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
Colonic polypGastrointestinal disorders
Other adverse events (16 terms — click to expand)

ReactionSystemWeeks 0-24: Placebo (Place…Weeks 0-24: Apremilast 20 …Weeks 0-24: Apremilast 30 …APR Exposure Period Up to …APR Exposure Period Up to …APR Exposure Period Up to …
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
HeadacheNervous system disorders
NasopharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
HypertensionVascular disorders
BronchitisInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
SinusitisInfections and infestations
Back painMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
VomitingGastrointestinal disorders
PharyngitisInfections and infestations
InsomniaPsychiatric disorders

Most-reported serious reactions: Psoriatic arthropathy, Osteoarthritis, Angina unstable, Pancreatitis acute, Pneumonia, Suicidal ideation, Hypertension, Anaemia.

Data from ClinicalTrials.gov NCT01212770 adverse events section.

Sponsor's own description

The purpose of this study is to determine whether apremilast is safe and effective in the treatment of patients with psoriatic arthritis and a qualifying psoriasis lesion. Apremilast is proposed to improve signs and symptoms of psoriatic arthritis (tender and swollen joints, pain, physical function) in treated patients.

Publications & conference data

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

  1. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3).
    Edwards CJ, Blanco FJ, Crowley J, Birbara CA, et al · · 2016 · cited 197× · PMID 26792812 · DOI 10.1136/annrheumdis-2015-207963
  2. The efficacy and safety of apremilast, etanercept and placebo in patients with moderate-to-severe plaque psoriasis: 52-week results from a phase IIIb, randomized, placebo-controlled trial (LIBERATE).
    Reich K, Gooderham M, Green L, Bewley A, et al · · 2017 · cited 129× · PMID 27768242 · DOI 10.1111/jdv.14015
  3. Phosphodiesterase 4-targeted treatments for autoimmune diseases.
    Kumar N, Goldminz AM, Kim N, Gottlieb AB. · · 2013 · cited 84× · PMID 23557064 · DOI 10.1186/1741-7015-11-96
  4. New developments in the management of psoriasis and psoriatic arthritis: a focus on apremilast.
    Palfreeman AC, McNamee KE, McCann FE. · · 2013 · cited 59× · PMID 23569359 · DOI 10.2147/dddt.s32713
  5. Clinical Implication of Phosphodiesterase-4-Inhibition.
    Schick MA, Schlegel N. · · 2022 · cited 56× · PMID 35163131 · DOI 10.3390/ijms23031209
  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. Long-term experience with apremilast in patients with psoriatic arthritis: 5-year results from a PALACE 1-3 pooled analysis.
    Kavanaugh A, Gladman DD, Edwards CJ, Schett G, et al · · 2019 · cited 53× · PMID 31077258 · DOI 10.1186/s13075-019-1901-3
  8. 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

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