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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV
ClinicalTrials.gov Identifier:
NCT01059773
First received: January 28, 2010
Last updated: May 13, 2014
Last verified: May 2014
  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:


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

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

Secondary Outcome Measures:
  • Rate of Adverse Events (AEs), Serious AEs (SAEs) and Deaths During the Study Period [ Time Frame: at week 12, 16, 28 40 and 52 ] [ Designated as safety issue: No ]
    The number of patients with any of the following Treatment Emergent AEs (TEAEs) were summarized through Week 12 and through Week 52, by treatment arm and body weight category (≤100 kg and >100 kg): AE; SAE and Death.

  • Rate of Severe AEs, Reasonably Related AEs, and AEs Leading to Discontination During the Study Period [ Time Frame: at week 12, 16, 28 40 and 52 ] [ Designated as safety issue: No ]
    The number of patients with any of the following TEAEs were summarized through Week 12 and through Week 52, by treatment arm and body weight category (≤100 kg and >100 kg): AE with severe intensity; AE or SAE reasonably related to ustekinumab (i.e., AEs classified by the investigator as 'possibly', 'probably', or 'very likely' related to study agent); AE or SAE leading to permanent discontinuation of ustekinumab.

  • Rate of Infections, Severe Infections and Infections Requiring Oral or Parenteral Antimicrobial Treatment During the Study Period [ Time Frame: at week 12, 16, 28 40 and 52 ] [ Designated as safety issue: No ]
    The number of patients with any of the following TEAEs were summarized through Week 12 and through Week 52, by treatment arm and body weight category (≤100 kg and >100 kg): infections, serious infections, and infections requiring oral or parenteral antimicrobial treatment (infections being considered any event that by the investigator was indicated as infection on the CRF).

  • Rate of Malignancies and Other Events of Clinical Interest (Tuberculosis, Serious Cardiovascular Events, Anaphylactic/Serum Sickness Reaction) [ Time Frame: at week 12, 16, 28 40 and 52 ] [ Designated as safety issue: No ]
    The number of patients with a malignancy and other event of clinical interest (tuberculosis, serious cardiovascular events, anaphylactic/serum sickness reaction) were summarized through Week 12 and through Week 52, by treatment arm and body weight category (≤100 kg and >100 kg)

  • Change in Mean Psoriasis Area-and-severity Index (PASI) Score Compared to Baseline [ Time Frame: at Weeks 0, 2, 4, 12, 16, 28, 40 and 52 ] [ Designated as safety issue: No ]
    Change from baseline in Psoriasis Area and Severity Index (PASI) (0 [best] - 72 [worst]). The PASI is a test of how bad a person's psoriasis is. The combination of redness, scaling, and thickness, as well as overall body involvement determine the PASI score.

  • Proportion of Patients Achieving PASI 50 Response [ Time Frame: at Weeks 2, 4, 12, 16, 28, 40 and 52 ] [ Designated as safety issue: No ]
    This is based on the number of participants achieving at least 50% improvement from baseline in Psoriasis Area and Severity Index (PASI) (0 [best] - 72 [worst]). The PASI is a test of how bad a person's psoriasis is. The combination of redness, scaling, and thickness, as well as overall body involvement determine the PASI score.

  • Proportion of Patients Achieving PASI 75 Response [ Time Frame: at Weeks 2, 4, 12, 16, 28, 40 and 52 ] [ Designated as safety issue: No ]
    This is based on the number of participants achieving at least 75% improvement from baseline in Psoriasis Area and Severity Index (PASI) (0 [best] - 72 [worst]). The PASI is a test of how bad a person's psoriasis is. The combination of redness, scaling, and thickness, as well as overall body involvement determine the PASI score.

  • Proportion of Patients Achieving PASI 90 Response [ Time Frame: at Weeks 2, 4, 12, 16, 28, 40 and 52 ] [ Designated as safety issue: No ]
    This is based on the number of participants achieving at least 90% improvement from baseline in Psoriasis Area and Severity Index (PASI) (0 [best] - 72 [worst]). The PASI is a test of how bad a person's psoriasis is. The combination of redness, scaling, and thickness, as well as overall body involvement determine the PASI score.


Enrollment: 490
Study Start Date: October 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.

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  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
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: NCT01059773

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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: Janssen-Cilag International NV
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: May 13, 2014
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
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 September 22, 2014