Phase II Study of Apremilast (CC-10004) in Adults With in Psoriatic Arthritis

NCT00456092 | Completed Phase 2 Results DMC

• 1 other identifier: CC-10004-PSA-001
• Study Type: interventional
• Target: 204
• Locations: 5 countries
• Sites: 38

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.

Conditions

Psoriatic Arthritis

Keywords

psoriatic arthritis; ACR; PASI; DAS; pharmacokinetic; biopsy

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Modified American College of Rheumatology 20% (ACR 20) Response at Week 12

  A modified American College of Rheumatology 20% (ACR 20) response was defined as a participant who met the following 3 criteria for improvement from Baseline: • ≥ 20% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal \[CMC\] and the distal interphalangeal \[DIP\] joints of the fingers); • ≥ 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's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[HAQ-DI\]); ◦ C-reactive protein. Participants with no post-baseline ACR scores were considered non-responders.

  Baseline and Week 12

Secondary Outcomes (41)

• Number of Participants With Adverse Events During the Treatment Phase

  12 weeks

• Percentage of Participants With a Psoriatic Arthritis Response Criteria (PsARC) Response at Week 12

  Baseline and Week 12

• Percentage of Participants With a Modified ACR 50 Response at Week 12

  Baseline and Week 12

• Percentage of Participants With a Modified ACR 70 Response at Week 12

  Baseline and Week 12

• Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response Based on Disease Activity Score (DAS28)-CRP(4) at Week 12

  Baseline and Week 12

Study Arms (3)

Apremilast 40 mg QD

EXPERIMENTAL

Participants received 40 mg apremilast orally once a day (QD) for 12 weeks in the Treatment Phase. Participants who entered the Extension Phase continued to receive 40 mg apremilast QD for an additional 12 weeks. The dose of apremilast was titrated starting at 10 mg QD during Days 1 to 3 followed by 20 mg QD during Days 4 to 7 and then 40 mg QD thereafter. A single dose reduction to 20 mg per day was allowed for participants who experienced intolerable adverse effects from study medication.

Drug: Apremilast

Apremilast 20 mg BID

EXPERIMENTAL

Participants received 20 mg apremilast orally twice a day (BID) for 12 weeks in the Treatment Phase. Participants who entered the Extension Phase continued to receive 20 mg apremilast BID for an additional 12 weeks. The dose of apremilast was titrated starting at 10 mg QD during Days 1 to 3 followed by 20 mg QD during Days 4 to 7 and then 20 mg BID thereafter. A single dose reduction to 20 mg per day was allowed for participants who experienced intolerable adverse effects from study medication.

Drug: Apremilast

Placebo

PLACEBO COMPARATOR

Participants received matching placebo to apremilast orally BID for 12 weeks during the Treatment Phase. Participants who entered the Extension Phase were re-randomized on Day 85 to receive either 40 mg apremilast QD or 20 mg apremilast BID for 12 weeks.

Drug: Placebo

Interventions

Apremilast DRUG

Capsules for oral administration

Also known as: CC-10004, Otezla®

Apremilast 20 mg BID; Apremilast 40 mg QD

Placebo DRUG

Capsules for oral administration

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (38)

CHU Brugmann

Brussels, 1020, Belgium

Location

Universiteit Hasselt

Diepenbeek, 3590, Belgium

Location

University Hospital

Leuven, 3000, Belgium

Location

Jan Palfijn Ziekenhuis

Merksem, 2170, Belgium

Location

The Arthritis Research Centre of Canada

Vancouver, British Columbia, V5Z 1L7, Canada

Location

Unknown Facility

Victoria, British Columbia, V8P4Y3, Canada

Location

Nexus Clinical Research

St. John's, Newfoundland and Labrador, A1B 3E1, Canada

Location

Burlington Rheumatology and Osteoporosis Clinic

Burlington, Ontario, L7R 4B7, Canada

Location

MAC Research Inc.

Hamilton, Ontario, L8N 2B6, Canada

Location

K-W Musculoskeletal Research Inc.

Kitchener, Ontario, N2M 5N6, Canada

Location

Credit Valley Rheumatology

Mississauga, Ontario, L5M 2V8, Canada

Location

Arthritis Program Research Group Inc

Newmarket, Ontario, L3Y 3R7, Canada

Location

Rheumatology Research Associates

Ottawa, Ontario, K1H 1A2, Canada

Location

Center for Prognosis Studies in the Rheumatic Diseases University Health Network, Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5T 3L9, Canada

Location

Probity Medical

Waterloo, Ontario, N2J1C4, Canada

Location

Clinical Research and Arthritis Centre

Windsor, Ontario, N8X 5A6, Canada

Location

West Island Rheumatology Research Associates

Pointe-Claire, Quebec, Canada

Location

Saskatoon Osteoporosis Center

Saskatoon, Saskatchewan, S7K 0H6, Canada

Location

Capio Franz von Prümmer Klinik

Bad Brückenau, 97769, Germany

Location

Free University of Berlin

Berlin, 10117, Germany

Location

Universitaetsklinik Koeln

Cologne, 50924, Germany

Location

Universitaetsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

Klinikum Eilbek

Hamburg, 22081, Germany

Location

Universitaet Heidelberg

Heidelberg, 69120, Germany

Location

Rheumazentrum Ruhrgebiet

Herne, 44652, Germany

Location

Universitaet Leipzig

Leipzig, 04103, Germany

Location

Universitaetsklinikum Leipzig

Leipzig, 04103, Germany

Location

University of Munich

Munich, 80336, Germany

Location

Klinikum der Universität Munster

Münster, 48149, Germany

Location

Friedrich-Alexander University, Erlangen

Nuremberg, 91054, Germany

Location

Leiden University Medical Centre

Leiden, 2300, Netherlands

Location

Radboud University

Nijmegen, 6500, Netherlands

Location

Hagaziekenhuis

The Hague, 2454 CH, Netherlands

Location

Hope Hospital

Salford, Manchester, M6 8HD, United Kingdom

Location

Haywood Hospital

Stoke-on-Trent, Staffs, ST6 7AG, United Kingdom

Location

Chapel Allerton Hospital

Leeds, LS7 4SA, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 22806399 BACKGROUND

• 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.

  PMID: 23588944 RESULT

MeSH Terms

Conditions

Arthritis, Psoriatic

Interventions

apremilast

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

1-888-260-1599

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2007
• First Posted: April 4, 2007
• Study Start: March 5, 2007
• Primary Completion: May 9, 2009
• Study Completion: May 9, 2009
• Last Updated: June 19, 2020
• Results First Posted: October 23, 2019

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

NL (3); DE (12); CA (15); BE (4); GB (4)