Clinical trial NCT00456092: Phase II Study of Apremilast (CC-10004) in Adults With in Psoriatic Arthritis
Official title: A Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Two Dose Regimens of CC-10004 in Subjects With Active Psoriatic Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Psoriatic Arthritis
Keywords: psoriatic arthritis
ACR
PASI
DAS
pharmacokinetic
biopsy
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2007-04-04
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is to look at the preliminary efficacy and safety of 2 dose regimens of apremilast (20 mg twice a day and 40 mg once a day) versus placebo in patients with active psoriatic arthritis.

Detailed description: Prior to the implementation of Amendment 1/UK3 the study consisted of 3 phases - pre-randomization up to 35 days, up to 84 days placebo-controlled treatment and a 28-day observational follow up. After the implementation of Amendment 1/UK3, the study consisted of 4 phases - pre-randomization up to 35 days, up to 84 days treatment in the placebo controlled treatment phase, up to 84 days treatment in the active treatment extension phase and a 28 day follow up. Participants who completed the treatment phase prior to implementation of amendment 1/UK3 did not have the option of entering the extension phase.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of psoriatic arthritis (Moll and Wright Criteria), including symmetrical or asymmetrical peripheral joint involvement for at least 6 months
* Active psoriatic arthritis at the time of screening and baseline as defined by: 3 or more swollen joints AND 3 or more tender joints
* Negative rheumatoid factor (RF)
* If using methotrexate, be on methotrexate for at least 168 days (24 weeks) and be on a stable dose for at least 56 days prior to screening and throughout the study
* If using oral corticosteroids, be on a stable dose of prednisone ≤ 10 mg/day or equivalent for at least 28 days prior to screening and throughout the study
* If using nonsteroidal anti-inflammatory drug (NSAID) therapy, be on a stable dose for at least 14 days prior to screening and throughout the study
* Must meet the following laboratory criteria:

  * Hemoglobin ≥ 9 g/dL
  * Hematocrit ≥ 27%
  * White blood cell (WBC) count ≥ 3000/μL (≥ 3.0 X 10\^9/L) and \< 20,000/μL (\< 20 X 10\^9/L)
  * Neutrophils ≥ 1500 /μL (≥ 1.5 X 10\^9/L)
  * Platelets ≥ 100,000 /μL (≥ 100 X 10\^9/L)
  * Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)
  * Total bilirubin ≤ 2.0 mg/dL
  * Aspartate transaminase (AST \[serum glutamic oxaloacetic transaminase, SGOT\]) and alanine transaminase (ALT \[serum glutamate pyruvic transaminase, SGPT\]) ≤ 1.5x upper limit of normal (ULN)
* Females of childbearing potential (FCBP) must have a negative urine pregnancy test at screening (Visit 1). In addition, sexually active FCBP must agree to use TWO adequate forms of contraception while on study medication. A FCBP must agree to have pregnancy tests every 28 days while on study medication
* Males (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in reproductive sexual activity with FCBP while on study medication and for at least 84 days after taking the last dose of study medication

Exclusion Criteria:

History of any clinically significant cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major diseases

* Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
* Pregnant or lactating female
* History of active Mycobacterium tuberculosis infection (any subspecies) within 3 years prior to the screening visit. Infections that occurred \> 3 years prior to entry must have been effectively treated.
* History of incompletely treated latent Mycobacterium tuberculosis infection (as indicated by a positive Purified Protein Derivative \[PPD\] skin test or in vitro test \[T SPOT®.TB, QuantiFERON Gold®\])
* Clinically significant abnormality on the chest x-ray (CXR) at screening
* Current erythrodermic, guttate, or pustular forms of psoriasis
* History of infected joint prosthesis within the past 5 years
* Systemic therapy for psoriasis and/or psoriatic arthritis (except for methotrexate, ≤ 10 mg/day prednisone or equivalent, and NSAIDs) including, but not limited to, sulfasalazine, leflunomide, chloroquine, hydroxychloroquine, gold compounds, parenteral corticosteroids (including intra-articular), penicillamine, cyclosporine, oral retinoids, mycophenolate mofetil, thioguanine, hydroxyurea, sirolimus, tacrolimus, azathioprine, and fumaric acid esters within 28 days of randomization and throughout the study
* Topical therapy for the treatment of psoriasis including, but not limited to topical steroids, topical vitamin A or D analog preparations, tacrolimus, pimecrolimus, or anthralin within 14 days of randomization (Note: Topical background therapy for treatment of psoriasis is allowed, except within 24 hours of a study visit, as follows: mild or moderate potency corticosteroids for treatment of the palms, face, scalp, axillae, plantar surfaces, and groin in accordance with the manufacturer's suggested usage. Nonmedicated emollients \[eg, Eucerin®\] and tar shampoo are also allowed.)
* Phototherapy (ultraviolet light A \[UVA\], narrow-band ultraviolet light B \[NB-UVB\], psoralens and long-wave ultraviolet radiation \[PUVA\]) within 28 days prior to randomization
* Etanercept use within 56 days prior to randomization
* Adalimumab, efalizumab, or infliximab use within 84 days prior to randomization
* Alefacept use within 168 days (24 weeks) prior to randomization
* Use of intra-articular corticosteroids within 28 days prior to randomization
* Use of any investigational medication within 28 days prior to randomization or 5 half-lives if known (whichever is longer)
* Any clinically significant abnormality on 12-lead electrocardiogram (ECG) at screening
* High-risk factor(s) for, or a history of, human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus infection
* History of malignancy within previous 5 years (except for treated basal-cell skin carcinoma(s) and/or fewer than 3 treated squamous-cell skin carcinomas)
* Evidence of skin conditions at the time of screening visit that would interfere with evaluations of the effect of study medication on psoriasis

Primary outcomes:
measure: Percentage of Participants With a Modified American College of Rheumatology 20% (ACR 20) Response at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Number of Participants With Adverse Events During the Treatment Phase
timeFrame: 12 weeks
measure: Percentage of Participants With a Psoriatic Arthritis Response Criteria (PsARC) Response at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants With a Modified ACR 50 Response at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants With a Modified ACR 70 Response at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response Based on Disease Activity Score (DAS28)-CRP(4) at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(3) at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants With DAS28-CRP(4) Score of Mild Disease Activity or In Remission at Week 12
timeFrame: Week 12
measure: Percentage of Participants With DAS28-CRP(3) Score of Mild Disease Activity or In Remission at Week 12
timeFrame: Week 12
measure: Number of Participants Who Withdrew Prematurely Due to Lack of Efficacy
timeFrame: Baseline to Week 12
measure: Number of Participants With Adverse Events Leading to a Dose Reduction
timeFrame: Baseline to Week 12
measure: Maximal ACR Response During the Treatment Phase
timeFrame: ACR was measured at Baseline and Weeks 2, 4, 6, 8, 10, and 12
measure: Time to ACR 20 Response During the Treatment Phase
timeFrame: Baseline to Week 12
measure: Time to ACR 50 Response During the Treatment Phase
timeFrame: Baseline to Week 12
measure: Time to ACR 70 Response During the Treatment Phase
timeFrame: Baseline to Week 12
measure: Change From Baseline in Dactylitis Severity Score at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants With Enthesitis
timeFrame: Baseline and Week 12
measure: Time to Relapse of Psoriatic Arthritis During the Observational Follow-up Phase
timeFrame: From Week 12 to end of 28-day observational follow-up (1) and from the date of maximal ACR during the 12-week Treatment Phase until the end of the 28-day observational follow-up phase (2).
measure: Number of Participants Who Relapsed During the Observational Follow-up Phase
timeFrame: 28-day observational follow-up period following Week 12
measure: Change From Baseline in Short Form 36 (SF-36) Summary Physical and Mental Component Scores at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-F) at Week 12
timeFrame: Baseline and Week 12
measure: Number of Participants With Adverse Events During the Extension Phase
timeFrame: Weeks 12 to 24 (Extension Phase)
measure: Percentage of Participants With a Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants With a Modified ACR 20 Response at Week 24
timeFrame: Baseline (Day 1), Week 12 (Day 85) and Week 24
measure: Percentage of Participants With a Modified ACR 50 Response at Week 24
timeFrame: Baseline (Day 1), Week 12 (Day 85) and Week 24
measure: Percentage of Participants With a Modified ACR 70 Response at Week 24
timeFrame: Baseline (Day 1) and Week 24
measure: Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(4) at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(3) at Week 24
timeFrame: Baseline and Week 24
measure: Maximal ACR Response During the Extension Period
timeFrame: ACR was measured at Baseline and Weeks 16, 20 and 24
measure: Time to ACR 20 Response During the Study
timeFrame: Baseline to Week 24
measure: Time to ACR 50 Response During the Treatment and Extension Phase
timeFrame: Baseline to Week 24
measure: Time to ACR 70 Response During the Treatment and Extension Phase
timeFrame: Baseline to Week 24
measure: Change From Baseline and Week 12 in Dactylitis Severity Score at Week 24
timeFrame: Baseline, Week 12 and Week 24
measure: Percentage of Participants With Enthesitis in the Extension Phase
timeFrame: Week 12 and Week 24
measure: Time to Relapse of Psoriatic Arthritis After Extension Phase
timeFrame: From Week 24 to the end of the 28-day follow-up (1) and from the date of maximal ACR until the end of the 28-day follow-up phase (2).
measure: Number of Participants Who Relapsed After the Extension Phase
timeFrame: Week 24 to Week 28 (28-day follow-up period)
measure: Change From Baseline and Week 12 in SF-36 at Week 24
timeFrame: Baseline (Day 1), Week 12 (Day 85) and Week 24
measure: Change From Baseline and Week 12 in Dermatology Life Quality Index (DLQI) at Week 24
timeFrame: Baseline (Day 1), Week 12 (Day 85) and Week 24
measure: Change From Baseline and Week 12 in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24
timeFrame: Baseline (Day 1), Week 12 (Day 85) and Week 24
measure: Change From Baseline in the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-F) at Week 24
timeFrame: Baseline (Day 1), Week 12 (Day 85) and Week 24
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: CHU Brugmann
city: Diepenbeek
country: Belgium
facility: Universiteit Hasselt
city: Leuven
country: Belgium
facility: University Hospital
city: Merksem
country: Belgium
facility: Jan Palfijn Ziekenhuis
city: Vancouver
country: Canada
facility: The Arthritis Research Centre of Canada
state: British Columbia
city: Victoria
country: Canada
state: British Columbia
city: St Johns
country: Canada
facility: Nexus Clinical Research
state: Newfoundland and Labrador
city: Burlington
country: Canada
facility: Burlington Rheumatology and Osteoporosis Clinic
state: Ontario
city: Hamilton
country: Canada
facility: MAC Research Inc.
state: Ontario
city: Kitchener
country: Canada
facility: K-W Musculoskeletal Research Inc.
state: Ontario
city: Mississauga
country: Canada
facility: Credit Valley Rheumatology
state: Ontario
city: Newmarket
country: Canada
facility: Arthritis Program Research Group Inc
state: Ontario
city: Ottawa
country: Canada
facility: Rheumatology Research Associates
state: Ontario
city: Toronto
country: Canada
facility: Center for Prognosis Studies in the Rheumatic Diseases University Health Network, Toronto Western Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Waterloo
country: Canada
facility: Probity Medical
state: Ontario
city: Windsor
country: Canada
facility: Clinical Research and Arthritis Centre
state: Ontario
city: Pointe-Claire
country: Canada
facility: West Island Rheumatology Research Associates
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Osteoporosis Center
state: Saskatchewan
city: Bad Brückenau
country: Germany
facility: Capio Franz von Prümmer Klinik
city: Berlin
country: Germany
facility: Free University of Berlin
city: Frankfurt
country: Germany
facility: Universitaetsklinikum Frankfurt
city: Hamburg
country: Germany
facility: Klinikum Eilbek
city: Heidelberg
country: Germany
facility: Universitaet Heidelberg
city: Herne
country: Germany
facility: Rheumazentrum Ruhrgebiet
city: Koeln
country: Germany
facility: Universitaetsklinik Koeln
city: Leipzig
country: Germany
facility: Universitaet Leipzig
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Munich
country: Germany
facility: University of Munich
city: Munster
country: Germany
facility: Klinikum der Universität Munster
city: Nuremberg
country: Germany
facility: Friedrich-Alexander University, Erlangen
city: Den Haag
country: Netherlands
facility: Hagaziekenhuis
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
city: Nijmegen
country: Netherlands
facility: Radboud University
city: Salford
country: United Kingdom
facility: Hope Hospital
state: Manchester
city: Stoke on Trent
country: United Kingdom
facility: Haywood Hospital
state: Staffs
city: Leeds
country: United Kingdom
facility: Chapel Allerton Hospital
city: Newcastle-upon-Tyne
country: United Kingdom
facility: Freeman Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Schett G, Wollenhaupt J, Papp K, Joos R, Rodrigues JF, Vessey AR, Hu C, Stevens R, de Vlam KL. Oral apremilast in the treatment of active psoriatic arthritis: results of a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2012 Oct;64(10):3156-67. doi: 10.1002/art.34627.
citation: Strand V, Schett G, Hu C, Stevens RM. Patient-reported Health-related Quality of Life with apremilast for psoriatic arthritis: a phase II, randomized, controlled study. J Rheumatol. 2013 Jul;40(7):1158-65. doi: 10.3899/jrheum.121200. Epub 2013 Apr 15.