An exploratory TRial to Assess Naturalistic Safety and efficacy outcomes In patients with moderate to severe plaque psoriasis Transitioned to ustekinumab from previous methotrexate therapy (TRANSIT) - TRANSIT

• Register: EUCTR
• Last refreshed on: 28 August 2012
• Main ID: EUCTR2008-008171-34-HU
• Date of registration: 11/06/2009
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: An exploratory TRial to Assess Naturalistic Safety and efficacy outcomes In patients with moderate to severe plaque psoriasis Transitioned to ustekinumab from previous methotrexate therapy (TRANSIT) - TRANSIT
• Scientific title: An exploratory TRial to Assess Naturalistic Safety and efficacy outcomes In patients with moderate to severe plaque psoriasis Transitioned to ustekinumab from previous methotrexate therapy (TRANSIT) - TRANSIT
• Date of first enrolment: 29/07/2009
• Target sample size: 576
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-008171-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: comparison with currently prescriped medication (MTX)

Countries of recruitment

Austria, Bulgaria, Denmark, Finland, France, Hungary, Italy, Lithuania, Netherlands, Portugal, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Potential patients must satisfy all of the following criteria to be enrolled in the study:
1. 18 years of age or older at time of consent.
2. 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).
3. Moderate-to-severe psoriasis scored as a PASI =10 at screening and at the time of first administration of ustekinumab.
4. Currently receiving (and have been receiving for at least 8 continuous weeks prior to screening) systemic therapy with methotrexate at an effective dose of at least = 10 mg/week =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.
5. Women of childbearing potential must be using adequate birth control measures throughout the study (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilisation). Women must agree to continue to use such birth control measures and not become pregnant or plan to become pregnant for at least 15 weeks after receiving the last dose of ustekinumab, and for at least 6 months after receiving the last dose of methotrexate. Breastfeeding is also not permitted throughout the study and for at least 15 weeks after the last dose of ustekinumab. All women of childbearing potential will undergo pregnancy testing before and during therapy (non-childbearing potential is defined as post menopausal for at least 1 year or surgical sterilisation or hysterectomy at least 3 months before study start).
6. Men must be using adequate birth control measures whilst receiving methotrexate, and for 6 months after the last dose of methotrexate.
7. Willing/able to adhere to the prohibitions and restrictions specified in this protocol.
8. Capable of giving informed consent; consent must be obtained in writing prior to any study related procedures.
9. Must agree not to receive a live virus or live bacterial vaccination during the study or for at least 15 weeks after last dose of study agent.
10. Must agree not to receive a Bacille Calmette-Guerin (BCG) vaccination during the study or up to 12 months after the last study agent injection.
11. Healthy on the basis of physical examination, medical history, and vital signs, performed at screening. If there are abnormalities, they must be consistent with the underlying illness in the study population.
12. Screening laboratory test results within the following parameters:
Haemoglobin = 10 g/dL
White blood cells = 3.5 x 109/L
Neutrophils = 1.5 x 109/L
Platelets = 100 x 109/L
Serum creatinine = 1.5 mg/dL (or = 133 mol/L)

Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase levels must not exceed two times the upper limit of the normal range for the laboratory conducting the test.
13. Eligible according to the following tuberculosis (TB) screening criteria:
a. No signs or symptoms suggestive of active TB upon medical history and/or physical examination.
b. No history of active or latent TB.
c. No recent close contact with a person with active TB.
d. Within 6 weeks prior to the first administration of study agent, have a negative TB test using EITHER a tuberculin skin test OR the QuantiFERON-TB Gold test (Attachment 2). TB testing should be interpreted using criteria for immunocompromised pati
Exclusion criteria:
Potential patients who meet any of the following criteria will be excluded from participating in the study:
1. Currently have non-plaque forms of psoriasis.
2. Currently receiving ciclosporin, fumarates, PUVA, etanercept, efalizumab, infliximab, adalimumab or alefacept.
3. Currently receiving any other systemic treatment (except methotrexate) that may improve psoriasis.
4. Currently receiving any other biologic agent.
5. Have received biologic therapy within the past 12 weeks or 5 half-lives of the agent, whichever is greater.
6. Have received natalizumab, efalizumab, or agents that deplete B or T cells within 12 months of screening, or, if after receiving these agents, evidence is available at screening of persistent depletion of the targeted lymphocyte population.
7. Have used any investigational drug within the previous 4 weeks or 5 half-lives of the investigational agent, whichever is longer.
8. Have received phototherapy or any systemic medications/treatments (except methotrexate) that could affect psoriasis or PASI evaluation within 2 weeks or 5 half-lives (whichever is longer) of the first ustekinumab injection.
9. Have received any topical treatments for psoriasis within 2 weeks or 5 half-lives (whichever is longer) of the first ustekinumab injection.
10. Have current drug-induced psoriasis
11. Pregnant, breastfeeding, or planning pregnancy while enrolled in the study.
12. 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 (briakinumab).
13. Are currently receiving lithium, antimalarials, or intramuscular gold or have received lithium, antimalarials, or intramuscular gold within 4 weeks of the first administration of study agent.
14. Have received, within 2 weeks prior to the first dose of ustekinumab, a live virus or bacterial vaccination. Patients must agree not to receive a live virus or bacterial vaccination during the study and for at least 15 weeks after the last dose of study agent.
15. Have received, or are expected to receive, a BCG vaccination within the 12 months prior screening, during the study, or within 12 months after the last administration of study agent.
16. Diagnosed with active or latent TB infection during screening.
17. Suffer from chronic or recurrent infectious disease, including but not limited to chronic renal infection; chronic chest infection; recurrent urinary tract infection (recurrent pyelonephritis or chronic nonremitting cystitis); or open, draining, or infected skin wounds or ulcers.
18. Have had or have a serious infection, or have been hospitalised or received IV antibiotics for an infection during the 2- month period prior to screening.
19. Have evidence of current active infection, including TB, or a nodule suspicious for lung malignancy on screening or any other available chest radiograph, unless definitively resolved surgically or by additional imaging and with source document confirmation.
20. Known to be infected with human immunodeficiency virus, hepatitis B, or hepatitis C.
21. Have previously had or have a nontuberculous mycobacterial infection or opportunistic infection
22. Have current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease.
23. Have a transplanted organ (with exception of a corneal transplant in situ for >3 months pri

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

moderate to severe plaque psoriasis
MedDRA version: 9.1 Level: LLT Classification code 10037153 Term: Psoriasis

Intervention(s)

Product Name: ustekinumab
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Ustekinumab
Other descriptive name: Anti IL 12 p40, human monoclonal antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 90-

Product Name: Methotrexate
Pharmaceutical Form: Tablet
INN or Proposed INN: Methotrexate
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 2.5-10

Product Name: Methotrexate
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Methotrexate
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 2.5-100

Primary Outcome(s)

Primary end point(s): The primary endpoint will be the proportion of patients experiencing one or more treatment emergent AEs through Week 12 in each treatment arm. Comparisons between arms will be descriptive only.

Main Objective: The primary objective of this exploratory trial is to evaluate the comparative safety through week 12 of two treatment transition strategies in patients with inadequate response to methotrexate: discontinuation of methotrexate with immediate initiation of ustekinumab versus initiation of ustekinumab with overlap and gradual dose reduction of methotrexate over 4 weeks.

Secondary Objective: - to evaluate the safety, efficacy, and quality of life associated with ustekinumab through Week 52
- to evaluate the effects of increasing the dose of ustekinumab from 45 mg to 90 mg at Week 28 and/or Week 40 in those patients (=100 kg) who do not achieve a PASI 75 response at Week 28 and/or Week 40

Secondary ID(s)

2008-008171-34-NL

CNTO1275PSO4004