Phase II Study With CC-10004 in Psoriatic Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00456092
First received: April 2, 2007
Last updated: November 22, 2013
Last verified: November 2013
  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
Drug: Matching Placebo
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:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • American College of Rheumatology Criteria for 20% improvement (ACR 20) [ Time Frame: Up to Day 169 ] [ Designated as safety issue: No ]
    Proportion of participants who achieve ACR 20


Secondary Outcome Measures:
  • Number of Participants with AEs [ Time Frame: Up to Day 169 ] [ Designated as safety issue: Yes ]
    Type, frequency, severity and relationship of adverse events to CC-10004

  • Number of participants prematurely discontinuing due to AEs [ Time Frame: Up to Day 169 ] [ Designated as safety issue: Yes ]
    Number of participants prematurely discontinuing due to any adverse event during all phases of treatment

  • Number of clinically significant changes AEs associated events related to a physical examination, vital signs, electrocardiogram (ECG) and/or laboratory findings [ Time Frame: Up to Day 169 ] [ Designated as safety issue: Yes ]
    Frequency of clinically significant changes AEs associated with a physical examination, vital signs, electrocardiogram (ECG) and/or laboratory findings during all treatment phases

  • The frequency that a participant is unable to withstand dose titration. [ Time Frame: Up to Day 169 ] [ Designated as safety issue: Yes ]
    Frequency of participants unable to withstand dose titration during the during all treatment periods

  • The frequency of participants who discontinue due to inability to withstand study medication adverse effects [ Time Frame: Up to Day 85& 169 ] [ Designated as safety issue: Yes ]
    Frequency of participants who discontinue due to inability to withstand study medication adverse effects during any treatment period

  • Psoriatic Arthritis Response Criteria (PsARC) [ Time Frame: Up to Day 85 & 169 ] [ Designated as safety issue: No ]
    Proportion of participants who meet PsARC, from baseline to Day 169

  • American College of Rheumatology Criteria for 50% improvement (ACR 50) [ Time Frame: Up to Day 85& 169 ] [ Designated as safety issue: No ]
    Proportion of participants who achieve ACR 50, from baseline to Day 169

  • American College of Rheumatology Criteria for 70% improvement (ACR 70) [ Time Frame: Up to Day 85 & 169 ] [ Designated as safety issue: No ]
    Proportion of participants who achieve ACR 70 from baseline to Day 169

  • American College of Rheumatology Criteria for 90% improvement (ACR 90) [ Time Frame: Up to Day 85 &169 ] [ Designated as safety issue: No ]
    Proportion of participants who achieve ACR 90 from baseline to Day 169

  • Change in Disease Activity Score (DAS28) [ Time Frame: Up to Day 85 & 169 ] [ Designated as safety issue: No ]
    Proportion of participants who achieve a 'good' or 'moderate' response according to DAS28 from baseline to Day 169

  • Disease Activity Score (DAS28) [ Time Frame: Up to Day 85 & 169 ] [ Designated as safety issue: No ]
    Proportion of participants whose disease severity is 'mild' or 'in remission' according to DAS from baseline to Day 169

  • Proportion of participants who withdraw prematurely due to lack of efficacy [ Time Frame: Up to Day 169 ] [ Designated as safety issue: No ]
    Proportion of participants who withdraw prematurely due to lack of efficacy from baseline to Day 169

  • Proportion of participants who dose reduce [ Time Frame: Up to Day 169 ] [ Designated as safety issue: Yes ]
    Proportion of participants who dose reduce from baseline through the end of the extension phase

  • American College of Rheumatology Criteria response [ Time Frame: Up to Day 85 & 169 ] [ Designated as safety issue: No ]
    Maximal ACR response from baseline to the end of the extension phase

  • American College of Rheumatology Criteria for 20% improvement (ACR 20) [ Time Frame: Up to Day 85 & 169 ] [ Designated as safety issue: No ]
    Time to achieve ACR 20 from baseline to the end of the extension phase

  • American College of Rheumatology Criteria for 50% improvement (ACR 50) [ Time Frame: Up to Day 85 & 169 ] [ Designated as safety issue: No ]
    Time to achieve ACR 50 from baseline to the end of the extension phase

  • American College of Rheumatology Criteria for 70% improvement (ACR 70) [ Time Frame: Up to Day 85 & 169 ] [ Designated as safety issue: No ]
    Time to achieve ACR 70 from baseline to the end of the extension phase

  • American College of Rheumatology Criteria for 90% improvement (ACR 90) [ Time Frame: Up to Day 85 & 169 ] [ Designated as safety issue: No ]
    Time to achieve ACR 90 from baseline to the end of the extension phase

  • Change in Dactylitis Score [ Time Frame: Up to Day 85 & 169 ] [ Designated as safety issue: No ]
    Change in dactylitis score from baseline through Day 169

  • Enthesitis incidence proportion [ Time Frame: Up to Day 85 & 169 ] [ Designated as safety issue: No ]
    Proportion of participants with and without enthesitis from baseline through Day 169

  • Time of Relapse of Psoriatic arthritis [ Time Frame: Up to Day 169 ] [ Designated as safety issue: No ]
    Time to relapse of psoriatic arthritis in participants who achieved at least an ACR 20 response from baseline through Day 169

  • Proportion of participants who relapsed during observational follow up [ Time Frame: Up to Day 169 ] [ Designated as safety issue: No ]
    Proportion of participants who relapsed during observational follow up

  • Change in Short Form 36 Version 2 (SF-36) [ Time Frame: Up to Day 85 & 169 ] [ Designated as safety issue: No ]
    Change in SF-36 Score, from baseline to Day 169

  • Change in Dermatology Life Quality Index (DLQI) [ Time Frame: Up to Day 85 & 169 ] [ Designated as safety issue: No ]
    Change in DLQI from baseline to Day 169

  • Change in the Health Assessment Questionnaire Disability Index (HAQ-DI) [ Time Frame: Up to Day 85 & 169 ] [ Designated as safety issue: No ]
    Change in HAQ-DI from baseline to Day 169

  • Change in the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-F) [ Time Frame: Up to Day 85 & 169 ] [ Designated as safety issue: No ]
    Change in SF-36 from baseline to Day 169

  • Change in T cell, B cell and NK cells in peripheral blood harmacodynamic (PD) [ Time Frame: Up to Day 85 ] [ Designated as safety issue: No ]
    Change in T cell, B cell and NK cells in peripheral blood at Day 85, and early termination from Treatment Phase visit from baseline to Day 169

  • Change in synovitis (synovium thickness and vascularity) and inflammatory markers in synovial tissue [ Time Frame: Up to Day 85 ] [ Designated as safety issue: No ]
    Change in synovitis (synovium thickness and vascularity) and inflammatory markers in synovial tissue from baseline to Day 85

  • Change in epidermal thickness and inflammatory markers in psoriatic skin [ Time Frame: Up to Day 85 ] [ Designated as safety issue: No ]
    Change in epidermal thickness and inflammatory markers in psoriatic skin from baseline to Day 85

  • Area under the plasma concentration-time curve from time 0 to 8 hours from dosing (AUC [ Time Frame: Day 71 ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve from time 0 to 8 hours from dosing (AUC)

  • Peak plasma concentration [ Time Frame: Day 71 ] [ Designated as safety issue: No ]
    Peak plasma concentration

  • Time to maximum plasma concentration [ Time Frame: Day 71 ] [ Designated as safety issue: No ]
    Time to maximum plasma concentration

  • Relationship of PK to PD and clinical outcomes) [ Time Frame: Day 71 ] [ Designated as safety issue: No ]
    Relationship of PK to PD and clinical outcomes


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
Experimental: Apremilast 20 mg
20mg CC-10004 orally twice a day (BID)
Drug: CC-10004
20mg CC-10004 twice a day orally following dose titration)
Other Name: Apremilast
Experimental: Apremilast 40 mg
40 mg CC-10004 orally every day (QD)
Drug: CC-10004
40 mg CC-10004 QD following dose titration
Other Name: Apremilast
Placebo Comparator: Placebo
Matching Placebo identical to CC-10004 orally BID or QD
Drug: Matching Placebo
: Placebo identical to CC-10004 orally BID or QD following dose titration

Detailed Description:

This study is to look at the preliminary efficacy and safety of CC-10004 vs placebo in patients with active psoriatic arthritis. Participants must have a minimum of 6 months history of psoriatic arthritis to qualify. Prior to the implementation of Amendment 1/UK3 the study was in 3 phases - pre-randomisation up to 35 days, up to 84 days treatment and a 28 day follow up. After the implementation of Amendment 1/UK3, the study is in 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. Treatment groups are 40 milligrams (mg) once daily (od), 20 mg twice daily (bd) or placebo. To ameliorate the dose dependent adverse events of CC-10004 (headache and gastro-intestinal (GI) disturbances) there will be dose titration of 10mg od (or placebo) for days 1 to 3 followed by 20 mg od (or placebo) days 4 to 7 in the first week of dosing. Patients changing from placebo to active treatment on entry to the extension phase will undergo dose titration of 10mg od for days 85 to 87 followed by 20mg od days 88 to 91. 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 placebo controlled treatment phase. Normal and psoriatic skin biopsies and/or synovial biopsies will be taken for evaluation of histopathology and biomarkers from subsets of patients 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 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 109/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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 38 Study Locations
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
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):
Responsible Party: 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: November 22, 2013
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
Apremilast
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on October 02, 2014