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

Purpose

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.

Condition	Intervention	Phase
Psoriasis	Drug: Ustekinumab Drug: Methotrexate	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Exploratory Trial to Assess Naturalistic Safety and Efficacy Outcomes in Patients With Moderate to Severe Plaque Psoriasis Transitiioned to Ustekinumab From Previous Methotrexate Therapy (TRANSIT)

Resource links provided by NLM:

MedlinePlus related topics: Psoriasis

Drug Information available for: Methotrexate Methotrexate sodium Ustekinumab

U.S. FDA Resources

Further study details as provided by Janssen-Cilag International NV:

Primary Outcome Measures:

Number of Patients Experiencing One or More Adverse Events Occuring From Week 0 Through Week 12 [ Time Frame: from week 0 to week 12 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Efficacy of Study Drug Measured Using Psoriasis Area & Severity Index (PASI) and Physician's Global Assessment (PGA) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Quality of Life as Measured by Changes in Dermatology Life Quality Index (DLQI), EuroQol-5D (EQ-5D) and Patient Benefit Index (PBI) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Rate of Adverse Events [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
Rate of AEs, Reasonably Related AEs/SAEs and Treated Infections [ Time Frame: each visit from week 0 to 52 ] [ Designated as safety issue: No ]
Rate of Malignancies [ Time Frame: each visit from week 0 to week 52 ] [ Designated as safety issue: No ]
Change in Mean/Median PASI Score Conpared to Baseline [ Time Frame: at week 0, 2, 4, 12, 16, 28, 40 and 52 ] [ Designated as safety issue: No ]

Enrollment:	490
Study Start Date:	September 2009
Study Completion Date:	August 2011
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Immediate Methotrexate Cessation 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 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.
Active Comparator: Gradual Reduction of Methotrexate 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 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. Drug: Methotrexate 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.

Arms

Assigned Interventions

Experimental: Immediate Methotrexate Cessation

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

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.

Active Comparator: Gradual Reduction of Methotrexate

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

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.

Drug: Methotrexate

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.

Show Detailed Description

Eligibility

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

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01059773

Show 76 Study Locations

Sponsors and Collaborators

Janssen-Cilag International NV

Investigators

Study Director:

Janssen-Cilag International NV Clinical Trial

Janssen-Cilag International NV

More Information

No publications provided

Responsible Party:	Medical Lead, Immunology, Neuro & Pain, Janssen-Cilag Ltd, United Kingdom
ClinicalTrials.gov Identifier:	NCT01059773 History of Changes
Other Study ID Numbers:	CR016639, CR016639, CNTO1275PSO4004
Study First Received:	January 28, 2010
Results First Received:	December 22, 2011
Last Updated:	March 13, 2012
Health Authority:	Belgium: Ministry of Social Affairs, Public Health and the Environment Germany: Ethics Commission

Keywords provided by Janssen-Cilag International NV:

Psoriasis
Ustekinumab
Stelara
Methotrexate
Biologic

Additional relevant MeSH terms:

Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Methotrexate
Antibodies, Monoclonal
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses

Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on May 21, 2013

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