A Safety and Efficacy Study of Ustekinumab in Patients With Plaque Psoriasis Who Have Had an Inadequate Response to Methotrexate

NCT01059773 | Completed Phase 4 Results DMC

• 2 other identifiers: CR016639CNTO1275PSO4004
• Study Type: interventional
• Target: 490
• Locations: 19 countries
• Sites: 76

Brief Summary

This purpose of this study is to assess the safety of ustekinumab in psoriasis patients who receive ustekinumab following an inadequate response to methotrexate therapy. The study will provide information for doctors on how to manage the transfer from methotrexate to the biologic agent ustekinumab. The study is designed to compare two methods of transferring patients from methotrexate to ustekinumab. The two methods being compared are discontinuation of methotrexate with immediate initiation of ustekinumab versus initiation of ustekinumab with overlap and gradual dose reduction of methotrexate over 4 weeks.

Conditions

Psoriasis

Keywords

Psoriasis; Ustekinumab; Stelara; Methotrexate; Biologic

Outcome Measures

Primary Outcomes (1)

• Number of Patients Experiencing One or More Adverse Events Occurring From Week 0 Through Week 12

  from week 0 to week 12

Secondary Outcomes (8)

• Rate of Adverse Events (AEs), Serious AEs (SAEs) and Deaths During the Study Period

  at week 12, 16, 28 40 and 52

• Rate of Severe AEs, Reasonably Related AEs, and AEs Leading to Discontination During the Study Period

  at week 12, 16, 28 40 and 52

• Rate of Infections, Severe Infections and Infections Requiring Oral or Parenteral Antimicrobial Treatment During the Study Period

  at week 12, 16, 28 40 and 52

• Rate of Malignancies and Other Events of Clinical Interest (Tuberculosis, Serious Cardiovascular Events, Anaphylactic/Serum Sickness Reaction)

  at week 12, 16, 28 40 and 52

• Change in Mean Psoriasis Area-and-severity Index (PASI) Score Compared to Baseline

  at Weeks 0, 2, 4, 12, 16, 28, 40 and 52

Study Arms (2)

Immediate Methotrexate Cessation

EXPERIMENTAL

Patients will receive ustekinumab by SC injection at Weeks 0, 4, 16, 28 and 40. The last dose of methotrexate will be taken anytime in the week prior to baseline (week 0).

Drug: Ustekinumab

Gradual Reduction of Methotrexate

ACTIVE COMPARATOR

Patients will receive ustekinumab by SC injection at Weeks 0, 4, 16, 28 and 40. Patients will gradually reduce the dose of methotrexate over the 4 week period after week 0.

Drug: Ustekinumab; Drug: Methotrexate

Interventions

Ustekinumab DRUG

Patients weighting ≤ 100 kg will receive ustekinumab 45 mg at Weeks 0, 4 and 16. Patients who achieve a PASI 75 response at Week 28 and 40 will continue receiving ustekinumab 45 mg at Week 28 and 40. Patients who fail to achieve PASI 75 response at Week 28 will receive ustekinumab 90 mg at Week 28 and 40. Patients who achieve a PASI 75 response at Week 28, but fail to achieve PASI 75 response at Week 40 will receive ustekinumab 90 mg at Week 40. Patients \> 100 kg will receive ustekinumab 90 mg at Weeks 0, 4, 16, 28 and 40, regardless of achievement of PASI 75 response. Consideration will be given to discontinuing treatment in these patients if they show no response at Week 28.

Gradual Reduction of Methotrexate; Immediate Methotrexate Cessation

Methotrexate DRUG

Gradual reduction of methotrexate therapy over the 4 week period after Week 0. The methotrexate dose reduction regime will depend on the dose of methotrexate at screening. All patients will stop methotrexate regardless of the final dose after 4 overlapping weeks. The last dose of methotrexate will be given within the 7 day period before the second dose of ustekinumab.

Gradual Reduction of Methotrexate

Eligibility Criteria

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

You may qualify if:

• Patients should have diagnosis of plaque-type psoriasis for at least 6 months prior to first administration of study agent (patients with concurrent psoriatic arthritis may be enrolled)
• Moderate-to-severe psoriasis scored as PASI \>= 10 at screening and at the time of first administration of ustekinumab
• Should currently receive (and have been receiving for at least 8 weeks directly prior to screening) systemic therapy with methotrexate at a dose of at least 10 mg/week but not exceeding 25 mg/week, with an inadequate response to this treatment (due to either efficacy or tolerability) and, in the judgment of the treating physician and patient, a treatment change is needed
• Women should take adequate birth control measures throughout the study and must agree to continue to use such birth control measures and not to become pregnant or plan to become pregnant for at least 15 weeks after the last dose of ustekinumab and for at least 6 months after the last dose of methotrexate
• Men must be using adequate birth control measures whilst receiving methotrexate and for 6 months after the last dose of methotrexate

You may not qualify if:

• Patients should not have non-plaque forms of psoriasis (eg, erythrodermic, guttate, or pustular)
• Should currently (and within 12 months) not receive ciclosporin, fumarates, PUVA, etanercept, efalizumab, infliximab, adalimumab or alefacept or other biologic or systemic therapy (and other therapy as indicated in the protocol)
• Women who are pregnant, breastfeeding, or planning pregnancy (both men and women) while enrolled in the study
• Have previously failed treatment with any therapeutic agent directly targeted at reducing IL-12 or IL-23, including, but not limited to, ustekinumab and ABT-874
• Active or latent Tuberculosis or other chronic or recurrent infectious disease
• Known history of lymphoproliferative disease
• Known malignancy or history of malignancy

Sponsors & Collaborators

• Janssen-Cilag International NV: lead

Study Sites (76)

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Vienna, Austria

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Brussels, Belgium

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Ghent, Belgium

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Liège, Belgium

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Pleven, Bulgaria

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Sofia, Bulgaria

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Aarhus, Denmark

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Roskilde, Denmark

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Tampere, Finland

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Turku, Finland

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Chambray-lès-Tours, France

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Creil, France

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Jarez, France

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Lille, France

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Marseille, France

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Montpellier, France

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Nantes, France

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Nantes Cedex 01 N/A, France

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Nice, France

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Paris, France

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Pessac, France

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Pierre-Bénite, France

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Poitiers, France

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Rouen, France

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Toulouse, France

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Berlin, Germany

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Dresden, Germany

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Erlangen, Germany

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Essen, Germany

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Frankfurt, Germany

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Göttingen, Germany

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Hamburg, Germany

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Kiel, Germany

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Landau, Germany

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Leipzig, Germany

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Mahlow, Germany

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Marburg, Germany

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München, Germany

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Münster, Germany

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Tÿbingen, Germany

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Witten, Germany

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Athens, Greece

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Thessaloniki, Greece

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Debrecen, Hungary

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Szeged, Hungary

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Petah Tikva, Israel

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Tel Aviv, Israel

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Kaunas, Lithuania

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Vilnius, Lithuania

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Nijmegen, Netherlands

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Rotterdam, Netherlands

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Oslo, Norway

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Stavanger, Norway

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Lodz, Poland

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Poznan, Poland

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Wroclaw, Poland

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Lisbon, Portugal

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Porto, Portugal

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Bratislava, Slovakia

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Alicante, Spain

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Badalona, Spain

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Barcelona, Spain

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Córdoba, Spain

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La Coruÿa N/A, Spain

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Madrid, Spain

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Gothenburg, Sweden

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Malmo, Sweden

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Solna, Sweden

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Uppsala, Sweden

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Aberdeen, United Kingdom

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Cardiff, United Kingdom

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Craigavon, United Kingdom

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Glasgow, United Kingdom

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London, United Kingdom

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Nottingham, United Kingdom

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Salford, United Kingdom

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MeSH Terms

Conditions

Psoriasis

Interventions

Ustekinumab; Methotrexate

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: EMEA THERAPEUTIC AREA LEADER
• Organization: Janssen-Cilag France

+33 6 15167408

Study Officials

• Janssen-Cilag International NV Clinical Trial

  Janssen-Cilag International NV

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2010
• First Posted: February 1, 2010
• Study Start: October 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: August 1, 2011
• Last Updated: November 24, 2014
• Results First Posted: January 30, 2012

Record last verified: 2014-11

Locations

NO (2); GR (2); BE (3); SE (4); AU (1); NL (2); BU (2); HU (2); PT (2); FR (15); ES (6); LI (2); PL (3); GB (7); DE (16); SL (1); DK (2); IL (2); FI (2)