Phase II Study With CC-10004 in Psoriatic Arthritis - Full Text View

Purpose

This study is to look at the preliminary efficacy and safety of CC-10004 vs placebo in patients with active psoriatic arthritis. The pharmacokinetics of the compound in patients will also be explored, and biopsies will be taken of the skin and the knee synovium to look at the activity of the drug in the relevant tissues.

Condition	Intervention	Phase
Psoriatic Arthritis	Drug: CC-10004	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of CC-10004 in Subjects With Active Psoriatic Arthritis

Resource links provided by NLM:

Genetics Home Reference related topics: psoriatic arthritis

U.S. FDA Resources

Further study details as provided by Celgene Corporation:

Primary Outcome Measures:

Proportion of subjects in each treatment group who achieve ACR criteria for 20% improvement at Day 85/Early termination visit compared with baseline [ Time Frame: Monthly ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Type, frequency, severity and relationship of adverse events to CC-10004; [ Time Frame: Two weekly ] [ Designated as safety issue: Yes ]
Number of subjects who prematurely discontinue study medication due to any adverse event; [ Time Frame: Two weekly ] [ Designated as safety issue: Yes ]
Frequency of clinically significant changes in physical examination, vital signs, ECG and/or laboratory findings [ Time Frame: Two weekly ] [ Designated as safety issue: Yes ]
Frequency of subjects unable to withstand dose titration [ Time Frame: Two weekly ] [ Designated as safety issue: Yes ]
Frequency of subjects who discontinue participation in the treatment phase due to inability to withstand over adverse effects of the study medication; [ Time Frame: Two weekly ] [ Designated as safety issue: Yes ]
Proportion of subjects in each treatment group who meet PsARC at Day 85/Day 169/early termination [ Time Frame: Day 85 and Day 169 ] [ Designated as safety issue: No ]
Proportion of subjects in each treatment group who achieve an ACR 50 and ACR 70 at Day 85/Day 169/early termination [ Time Frame: Day 85 and Day 169 ] [ Designated as safety issue: No ]
Change in DAS of subjects in each treatment group at D85/Day 169/early termination [ Time Frame: Day 85 and Day 169 ] [ Designated as safety issue: No ]
Change in PASI score at Day 85/Day 89/ET [ Time Frame: Day 85 and Day 169 ] [ Designated as safety issue: No ]
Proportion of subjects in each treatment group who achieve >= PASI 50 at D85/Day 169/ET [ Time Frame: Day 85 and Day 169 ] [ Designated as safety issue: No ]
Maximal ACR response during treatment [ Time Frame: Once ] [ Designated as safety issue: No ]
Maximal PASI response during treatment [ Time Frame: Once ] [ Designated as safety issue: No ]
Time to achieve ACR 20/50/70 [ Time Frame: Once ] [ Designated as safety issue: No ]
Time to achieve PASI 50 [ Time Frame: Once ] [ Designated as safety issue: No ]
Change in dactylitis severity score in subjects in each treatment group at D85/Day 169/ET [ Time Frame: Day 85 and Day 169 ] [ Designated as safety issue: No ]
Proportion of subjects with and without enthesitis in each treatment group at D85/Day 169/ET [ Time Frame: Day 85 and Day 169 ] [ Designated as safety issue: No ]
Time to relapse of psoriasis during observational follow up [ Time Frame: Once ] [ Designated as safety issue: No ]
Time to relapse of psoriatic arthritis during observational follow up [ Time Frame: Once ] [ Designated as safety issue: No ]
Proportion of subjects who relapse during observational follow up [ Time Frame: Once ] [ Designated as safety issue: No ]
Change from baseline in QOL assessment scores at D85/Day 169/ET [ Time Frame: Day 85 and Day 169 ] [ Designated as safety issue: No ]
Change in peripheral blood T cell, B cell and NK cell subsets [ Time Frame: Two weekly ] [ Designated as safety issue: No ]
Change in synovitis and change in inflammatory markers in synovial tissue at D85/ET [ Time Frame: Once ] [ Designated as safety issue: No ]
Change in epidermal thickness and change in inflammatory markers in psoriatic skin biopsies at D85/ET [ Time Frame: Once ] [ Designated as safety issue: No ]
Pharmacokinetic profile including AUC, Cmax, Tmax and relationship of PK to PD and clinical outcomes [ Time Frame: Day 71/Day 85 ] [ Designated as safety issue: No ]

Enrollment:	204
Study Start Date:	January 2009
Study Completion Date:	May 2009
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: A 20mg bid	Drug: CC-10004 Comparison of two active doses of CC-10004 (20mg bid and 40mg od) vs placebo
Active Comparator: B 40mg od	Drug: CC-10004 Comparison of two active doses of CC-10004 (20mg bid and 40mg od) vs placebo
Placebo Comparator: C Matching placebo	Drug: CC-10004 Comparison of two active doses of CC-10004 (20mg bid and 40mg od) vs placebo

Detailed Description:

This study is to look at the preliminary efficacy and safety of CC-10004 vs placebo in patients with active psoriatic arthritis. Subjects must have a minimum of 6 months history of psoriatic arthritis to qualify. The study is in 3 phases - pre-randomisation of up to 35 days, up to 84 days treatment and a 28 day observational follow up. Treatment groups are 40mg CC-10004 od, 20mg CC-10004 bd or placebo. To ameliorate the dose dependent adverse events of CC-10004 (headache and GI disturbances) there will be dose titration of 10mg od (or placebo)for days 1-3 followed by 20mg od (or placebo) days 4 to 7 in the first week of dosing. Assessments take place after week 1 and then every 2 weeks during the treatment phase.

Plasma pharmacokinetics of CC-10004 will be evaluated in a subset of patients from each active treatment group during the treatment phase. Normal and psoriatic skin biopsies and/or synovial biopsies will be taken for evaluation of histopathology and biomarkers from subsets of subjects in each treatment group.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 defined as at least 3 tender and at least 3 swollen joints
negative RF
if on MTX, must be on for at least 24 weeks and on stable dose at least 56 days before screening
if on oral steroids, must be on stable dose of prednisone <=10mg/day or equivalent for 28 days
if on NSAID, must be on a stable dose at least 14 days prior to screening
Lab criteria: Hb >9g/dL, HCT >27%, WBC >3000/uL and <20000/uL, neut >1500/uL, platelets >100,000/uL, creatinine <1.5mg/dL, total bilirubin <2.0mg/dL, AST and ALT < 1.5 ULN
FCBP must have negative pregnancy tests and be on two forms of contraception throughout the study
Males must use barrier contraception with FCBP partner

Exclusion Criteria:

clinically significant diseases
any condition placing subject at risk
pregnant or lactating females
history of TB infection within 3 years
history of incompletely treated latent TB
clinically significant abnormality on CXR at screening
current erythrodermic, guttate or pustular psoriasis
history of infected joint prosthesis within 5 years
systemic therapy including sulphasalazine, leflunomide, chloroquine, hydroxychloroquine, gold, parenteral steroids, penicillamine, cyclosporine, oral retinoids, mycophenolate mofetil, thioguanine, hydroxyurea, sirolimus, tacrolimus, azathioprine and fumaric acid esters within 28 days of randomization
topical therapy for treatment of psoriasis within 14 days of randomization (except mild or moderate steroids and non medicated emollients)
phototherapy within 28 days randomization
etanercept within 56 days randomization
Adalimumab, efalizumab, or infliximab within 84 days randomization
alefacept within 24 weeks randomization
use of any intra-articular steroids within 28 days randomization
use of any investigational medication within 28 days randomization or 5 half-lives whichever is longer
clinically significant abnormality on ECG at screening
high risk factors for HIV or hepatitis B or C
history of malignancy within 5 years (except basal cell skin carcinomas and/or fewer than 3 treated squamous cell skin carcinomas
evidence of skin conditions at screening that would interfere with evaluations of psoriasis

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00456092

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Locations

Belgium
CHU Brugmann
Brussels, Belgium, 1020
Universiteit Hasselt
Diepenbeek, Belgium, 3590
University Hospital
Leuven, Belgium, 3000
Jan Palfijn Ziekenhuis
Merksem, Belgium, 2170
Canada, British Columbia
The Arthritis Research Centre of Canada
Vancouver, British Columbia, Canada, V5Z 1L7

Victoria, British Columbia, Canada, V8P4Y3
Canada, Newfoundland and Labrador
Nexus Clinical Research
St Johns, Newfoundland and Labrador, Canada, A1B 3E1
Canada, Ontario
Burlington Rheumatology and Osteoporosis Clinic
Burlington, Ontario, Canada, L7R 4B7
MAC Research Inc.
Hamilton, Ontario, Canada, L8N 2B6
K-W Musculoskeletal Research Inc.
Kitchener, Ontario, Canada, N2M 5N6
Credit Valley Rheumatology
Mississauga, Ontario, Canada, L5M 2V8
Arthritis Program Research Group Inc
Newmarket, Ontario, Canada, L3Y 3R7
Rheumatology Research Associates
Ottawa, Ontario, Canada, K1H 1A2
Center for Prognosis Studies in the Rheumatic Diseases University Health Network, Toronto Western Hospital
Toronto, Ontario, Canada, M5T 2S8
Mount Sinai Hospital
Toronto, Ontario, Canada, M5T 3L9
Probity Medical
Waterloo, Ontario, Canada, N2J1C4
Clinical Research and Arthritis Centre
Windsor, Ontario, Canada, N8X 5A6
Canada, Quebec
West Island Rheumatology Research Associates
Pointe-Claire, Quebec, Canada
Canada, Saskatchewan
Saskatoon Osteoporosis Center
Saskatoon, Saskatchewan, Canada, S7K 0H6
Germany
Capio Franz von Prümmer Klinik
Bad Brückenau, Germany, 97769
Free University of Berlin
Berlin, Germany, 10117
Universitaetsklinikum Frankfurt
Frankfurt, Germany, 60590
Klinikum Eilbek
Hamburg, Germany, 22081
Universitaet Heidelberg
Heidelberg, Germany, 69120
Rheumazentrum Ruhrgebiet
Herne, Germany, 44652
Universitaetsklinik Koeln
Koeln, Germany, 50924
Universitaet Leipzig
Leipzig, Germany, 04103
Universitaetsklinikum Leipzig
Leipzig, Germany, 04103
University of Munich
Munich, Germany, 80336
Klinikum der Universität Munster
Munster, Germany, 48149
Friedrich-Alexander University, Erlangen
Nuremberg, Germany, 91054
Netherlands
Hagaziekenhuis
Den Haag, Netherlands, 2454 CH
Leiden University Medical Centre
Leiden, Netherlands, 2300
Radboud University
Nijmegen, Netherlands, 6500
United Kingdom
Hope Hospital
Salford, Manchester, United Kingdom, M6 8HD
Haywood Hospital
Stoke on Trent, Staffs, United Kingdom, ST6 7AG
Chapel Allerton Hospital
Leeds, United Kingdom, LS7 4SA
Freeman Hospital
Newcastle-upon-Tyne, United Kingdom, NE7 7DN

Sponsors and Collaborators

Celgene Corporation

Investigators

Principal Investigator:	Edward Keystone	Mount Sinai Hospital, Rebecca MacDonald Centre for Arthritis and Auto-immune disease, Toronto
Principal Investigator:	Carter Thorne	Arthritis Program Research Group, Ontario
Principal Investigator:	Kurt de Vlam	Universitaire Ziekenhuizen Leuven
Principal Investigator:	P Geusens	Universiteit Hasselt, Diepenbiek
Principal Investigator:	Jacques Bentin	CHU Brugmann Dept Rheumatology, Brussels
Principal Investigator:	Rik Joos	Jan Palfijn Ziekenhuis, Merksem
Principal Investigator:	Georg Schett	Friedrich-Alexander-University, Erlangen
Principal Investigator:	Gerd Burmester	Free University of Berlin
Principal Investigator:	Harald Burkhardt	Universitaetsklinikum Frankfurt
Principal Investigator:	Holm Haentzschel	Universitaet Leipzig
Principal Investigator:	Martin Lorenz	Universitaet Heidelberg
Principal Investigator:	Andrea Rubbert	Universitaetsklinik Koeln
Principal Investigator:	Jan Simon	Universitaetsklinikum Leipzig, Dept of Dermatology
Principal Investigator:	Jurgen Wollenhaupt	Klinikum Eilbek, Hamburg
Principal Investigator:	Piet van Riel	Radboud University Nijmegen
Principal Investigator:	T W Huizinga	Leiden University Medical Centre
Principal Investigator:	H K Ronday	Hagaziekenhuis, Den Haag
Principal Investigator:	Paul Emery	Chapel Allerton Hospital, Leeds
Principal Investigator:	Robert G Cooper	Hope Hospital, Salford, Manchester
Principal Investigator:	Andrew Ostor	Addenbrooke's Hospital, Cambridge
Principal Investigator:	Bruce Kirkham	Guys and St Thomas' Hospital, London
Principal Investigator:	John Packham	Haywood Hospital, Stoke on Trent
Principal Investigator:	David Walker	Freeman Hospital, Newcastle
Study Director:	Wei Zhu, MD	Celgene Corporation

More Information

No publications provided by Celgene Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	VP Clinical R&D Rheumatology, Celgene Corporation
ClinicalTrials.gov Identifier:	NCT00456092 History of Changes
Other Study ID Numbers:	CC-10004-PsA-001
Study First Received:	April 2, 2007
Last Updated:	February 1, 2010
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices United Kingdom: Medicines and Healthcare Products Regulatory Agency Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Canada: Health Canada

Keywords provided by Celgene Corporation:

psoriatic arthritis
ACR
PASI

DAS
pharmacokinetic
biopsy

Additional relevant MeSH terms:

Arthritis
Arthritis, Psoriatic
Joint Diseases
Musculoskeletal Diseases
Spondylarthropathies
Spondylarthritis

Spondylitis
Spinal Diseases
Bone Diseases
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases

ClinicalTrials.gov processed this record on May 19, 2013